• Section 1c: Update of ‘Expiration date’ to ‘Expiry date’.
• Commonly asked questions:

Q. What if the pre-filled pen is left at room temperature for longer than 30 minutes?

A. If needed, the pre-filled pen may be left out of the fridge at temperature not above 30 °C for up to 5 days if protected from direct sunlight. Taltz should be discarded if not used within the 5 day period at room temperature.

• Updated date of revision.

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Added (underline) deleted (strikethrough)

HEADER (pen)

Ireland, United Kingdom (Northern Ireland), Malta

TA022

6.             Contents of the pack and other information

What Taltz contains

-          The active substance is ixekizumab.

            Each pre‑filled syringe contains 80 mg of ixekizumab in 1 ml solution.

-          The other ingredients are sodium citrate; citric acid, anhydrous; sodium chloride sucrose; polysorbate 80; water for injections. In addition, sodium hydroxide may have been added for pH adjustment.

This leaflet was last revised in August December 2021

Other sources of information (pen)

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

TA030

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Added (underline) deleted (strikethrough)

4.8         Undesirable effects

Tabulated list of adverse reactions

Adverse reactions from clinical studies and postmarketing reports (Table 1) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions is are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000).

 ….

The increased frequency of injection site reactions in the combined Q2W and Q4W groups did not result in an increase in discontinuations in either the plaque psoriasis, the psoriatic arthritis or the axial spondyloarthritis studies.

The results described above are obtained with the original formulation of Taltz. In a single-blinded, randomized cross-over study in 45 healthy subjects comparing the original formulation with the revised, citrate-free formulation, statistically significantly lower VAS pain scores were obtained with the citrate-free vs. the original formulation during injection (difference in LS Mean VAS score -21.69) and 10 min after injection (difference in LS Mean VAS score -4.47).

5.1         Pharmacodynamic properties

….

Of 591 subjects who received Taltz Q2W during the Induction Period then Q4W afterward in study UNCOVER‑1, UNCOVER‑2, and UNCOVER‑3, 427 subjects completed 5 years of Taltz treatment, among those 101 patients required a dose escalation. Among the patients who completed the wWeek 264 assessment (N=427), 295 patients (69%), 289 patients (68%) and 205 patients (48%) were observed to have sPGA (0,1), PASI 90 and PASI 100 response, respectively, at wWeek 264. DLQI were collected after Induction Period in UNCOVER‑1 and UNCOVER‑2, 113 patients (66%) were observed to have DLQI (0,1) response.

….

Psoriatic arthritis

Taltz was assessed in two randomised, double-blind, placebo-controlled phase III studies in 780 patients with active psoriatic arthritis (≥ 3 swollen and ≥ 3 tender joints). Patients had a diagnosis of psoriatic arthritis (Classification Criteria for Psoriatic Arthritis [CASPAR] criteria) for a median of 5.33 years and had current plaque psoriasis skin lesions (94.0 %) or a documented history of plaque psoriasis, with 12.1 % of patients with moderate to severe plaque psoriasis at baseline. Over 58.9 % and 22.3 % of the psoriatic arthritis patients had enthesitis and dactylitis at baseline, respectively.  Primary endpoint of both studies was American College of Rheumatology (ACR) 20 response at week 24, followed by a long‑term extension period from wWeek 24 to wWeek 156 (3 years)

…

In SPIRIT‑P1, 63 patients completed 3 years of Q4W ixekizumab treatment. Among the 107 patients who were randomized to ixekizumab Q4W (NRI analysis in ITT population), 54 patients (50%), 41 patients (38%), 29 patients (27%), and 36 patients (34%) were observed to have ACR20, ACR50, ACR70, and MDA response, respectively, at wWeek 156.

In SPIRIT‑P2, 70 patients completed 3 years of Q4W ixekizumab treatment. Among the 122 patients who were randomized to ixekizumab Q4W (NRI analysis in ITT population), 56 patients (46%), 39 patients (32%), 24 patients (20%) and 33 (27%) were observed to have ACR20, ACR50, ACR70, and MDA response, respectively, at wWeek 156.

….

Taltz was superior to ADA on the primary study objective: simultaneous achievement of ACR 50 and PASI 100 response at week 24 (Taltz 36.0% vs ADA 27.9%; p=0.036; 95% confidence interval [0.5%, 15.8%]). Taltz also showed non-inferiority (pre-specified margin of -12%) to ADA on ACR 50 (ITT analysis: Taltz 50.5% vs ADA 46.6%; 3.9% difference vs. ADA; 95% confidence interval [-4.3%; 12.1%] ; PPS analysis Taltz: 52.3%, ADA: 53.1%, difference: -0.8% [CI: -10.3%; 8.7%]) and superiority on PASI 100 at week 24 (60.1 % with Taltz vs 46.6% with ADA, p=0.001), which were the major secondary endpoints in the study. At wWeek 52 a higher proportion of patients treated with Taltz versus ADA simultaneously achieved ACR50 and PASI 100 [39% (111/283) versus 26% (74/283)] and PASI 100 [64% (182/283) versus 41% (117/283)]. Taltz and ADA treatment resulted in similar responses for ACR50 [49.8% (141/283) versus 49.8% (141/283)]. Responses to Taltz were consistent when used as monotherapy or with concomitant use of methotrexate.

….

Radiographic axial spondyloarthritis

….

COAST-V evaluated 341 biologic-naive patients, treated with either Taltz 80 mg or 160 mg at week 0 followed by 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), adalimumab 40 mg every 2 weeks, or with placebo.

….

In patients who received Taltz Q4W continuously (N=157), the ASAS40, ASDAS<2.1 and BASDAI50 responses were maintained to wWeek 116.

6.1         List of excipients

Sodium citrate

Citric acid, anhydrous

Sodium chloride

Sucrose

Polysorbate 80

Water for injections

Sodium hydroxide may be used to adjust pH

7.        MARKETING AUTHORISATION HOLDER

 Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands Eli Lilly and Company (Ireland) Limited, Dunderrow, Kinsale, Co. Cork, Ireland.

10.      DATE OF REVISION OF THE TEXT
12 August 20 July 2021
 

6. Contents of the pack and other information
[…]
Marketing Authorisation Holder
Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands. Eli Lilly and Company (Ireland) Limited, Dunderrow, Kinsale, Co. Cork, Ireland.
[…]
This leaflet was last revised in July August 2021

Changes

Added (underline) deleted (strikethrough)

• Table and Figure numbers updated
• Formatting updates made throughout the document

4.8          Undesirable effects

[…]

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Ireland HPRA Pharmacovigilance, Website: www.hpra.ie, Malta: ADR Reporting Website: www.medicinesauthority.gov.mt/adrportal, United Kingdom (Northern Ireland)

Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

5.1          Pharmacodynamic properties

[…]

Adult plaque psoriasis

The efficacy and safety of Taltz were assessed in three randomised, double-blind, placebo-controlled phase III studies in adult patients (N=3,866) with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy (UNCOVER-1, UNCOVER-2, and UNCOVER-3). The efficacy and safety of Taltz were also evaluated versus etanercept (UNCOVER-2 and UNCOVER-3). Patients randomised to Taltz who were sPGA (0,1) responders (static Physicians Global Assessment) at week 12 were re-randomised to receive placebo or Taltz for an additional 48 weeks (UNCOVER-1 and UNCOVER-2); patients randomised to placebo, etanercept or Taltz who were sPGA (0,1) non-responders received Taltz for up to 48 weeks. In addition, long‑term efficacy and safety were evaluated in all three studies for up to a total of 5 years in patients who participated through the entire study.

[…]

Maintenance of response at week 60 and up to 5 years

Patients originally randomised to Taltz and who were responders at week 12 (i.e., sPGA score of 0,1) in UNCOVER-1 and UNCOVER-2 were re-randomised to an additional 48 weeks of treatment with placebo or Taltz (80 mg every four or twelve weeks [Q4W or Q12W]).

For sPGA (0,1) responders at week 12 re‑randomised to treatment withdrawal (i.e., placebo), the median time to relapse (sPGA ≥ 3) was 164 days in integrated UNCOVER‑1 and UNCOVER‑2 studies. Among these patients, 71.5 % regained at least an sPGA (0,1) response within 12 weeks of restarting treatment with Taltz 80 mg Q4W.

[…]

Of 591 subjects who received Taltz Q2W during the Induction Period then Q4W afterward in study UNCOVER‑1, UNCOVER‑2, and UNCOVER‑3, 427 subjects completed 5 years of Taltz treatment, among those 101 patients required a dose escalation. Among the patients who completed the Week 264 assessment (N=427), 295 patients (69%), 289 patients (68%) and 205 patients (48%) were observed to have sPGA (0,1), PASI 90 and PASI 100 response, respectively, at Week 264. DLQI were collected after Induction Period in UNCOVER‑1 and UNCOVER‑2, 113 patients (66%) were observed to have DLQI (0,1) response.

[…]

Postmarketing phase 3b, direct comparative studiesy
IXORA-S: In a double-blind study Taltz ixekizumab was superior against ustekinumab on the primary study objective PASI 90 response at week 12 (Table 6). Onset of response was superior on PASI 75 as early as week 2 (p < 0.001) and on PASI 90 and PASI 100 by week 4 (p < 0.001). Superiority of Taltz ixekizumab versus ustekinumab was also demonstrated in the subgroups stratified by weight.

Table 6. PASI-response rates from comparative study ixekizumab versus ustekinumab

* Ixekizumab 160 mg given as a loading dose followed by 80 mg at week 2,4,6,8,10 and 12, and 80 mg Q4W thereafter
** Weight based dosing: Patients treated with ustekinumab received 45 mg or 90 mg at weeks 0 and 4, then every 12 weeks until week 52 (dosed by weight as per approved posology)
^§p < 0.001 versus ustekinumab (p value only provided for primary endpoint)

IXORA‑R: Efficacy and safety of Taltz was also investigated in a 24‑week randomized, double‑blind, parallel‑group study comparing Taltz to guselkumab, with Taltz being superior as early as Week 4 in achieving complete skin clearance and on the primary study objective (PASI 100 at week 12) and non‑inferior on PASI 100 at Week 24 (Table 7).

Table 7. Efficacy Responses from comparative study ixekizumab versus guselkumab, Intent‑to‑Treat Population^a

Abbreviations: CI = confidence interval; GUS = guselkumab; IXE = ixekizumab; N = number of patients in the analysis population; n = number of patients in the specified category; PASI = psoriasis area and severity index; sPGA = static physician global assessment.

^a Endpoints were gated in this order

Figure 2: PASI 100 at weeks 4, 8, 12 and 24, NRI

*p<0.001 vs guselkumab at weeks 4, 8, and 12
NRI = Non-Responder Imputation

[…]

Table 78.              Efficacy results at week 12 in adults with genital psoriasis in trial IXORA-Q; NRI ^a

[…]

The clinical response data are presented in Table 89.

Table 89.         Efficacy results in pediatric patients with plaque psoriasis, NRI

[…]

Figure 23. Percent of patients achieving PASI 75 in pediatric psoriasis through week 12

[…]

Psoriatic arthritis

Taltz was assessed in two randomised, double-blind, placebo-controlled phase III studies in 780 patients with active psoriatic arthritis (≥ 3 swollen and ≥ 3 tender joints). Patients had a diagnosis of psoriatic arthritis (Classification Criteria for Psoriatic Arthritis [CASPAR] criteria) for a median of 5.33 years and had current plaque psoriasis skin lesions (94.0 %) or a documented history of plaque psoriasis, with 12.1 % of patients with moderate to severe plaque psoriasis at baseline. Over 58.9 % and 22.3 % of the psoriatic arthritis patients had enthesitis and dactylitis at baseline, respectively.  Primary endpoint of both studies was American College of Rheumatology (ACR) 20 response at week 24, followed by a long‑term extension period from Week 24 to Week 156 (3 years).

In Psoriatic Arthritis Study 1 (SPIRIT-P1), patients naive to biologic therapy with active psoriatic arthritis were randomised to placebo, adalimumab 40 mg once every 2 weeks (active control reference arm), Taltz 80 mg once every 2 weeks (Q2W), or 80 mg once every 4 weeks (Q4W). Both Taltz regimens included a 160 mg starting dose. 85.3 % of patients in this study had received prior treatment with ≥ 1 cDMARD. 53 % of patients had concomitant use of MTX at a mean weekly dose of 15.8 mg. 67 % of patients who had concomitant use of MTX had a dose of 15 mg or greater. Patients with an inadequate response at week 16 received rescue therapy (modification to background therapy). Patients on Taltz Q2W or Q4W remained on their originally assigned dose of Taltz. Patients receiving adalimumab or placebo were re-randomised 1:1 to Taltz Q2W or Q4W at week 16 or 24 based on responder status. 243 patients completed the extension period of 3 years on Taltz.

Psoriatic Arthritis Study 2 (SPIRIT-P2) enrolled patients who were previously treated with an anti-TNF agent and discontinued the anti-TNF agent for either lack of efficacy or intolerance (anti-TNF-IR patients). Patients were randomised to placebo, Taltz 80 mg once every 2 weeks (Q2W), or 80 mg once every 4 weeks (Q4W).  Both Taltz regimens included a 160 mg starting dose. 56 % and 35 % of patients were inadequate responders to 1 anti-TNF or 2 anti-TNF, respectively.  SPIRIT-P2 evaluated 363 patients, of whom 41 % had concomitant use of MTX at a mean weekly dose of 16.1 mg. 73.2 % of patients who had concomitant use of MTX had a dose of 15 mg or greater. Patients with an inadequate response at week 16 received rescue therapy (modification to background therapy). Patients in Taltz Q2W or Q4W remained on their originally assigned dose of Taltz. Patients receiving placebo were re-randomised 1:1 to Taltz Q2W or Q4W at week 16 or 24 based on responder status. 168 patients completed the extension period of 3 years on Taltz.

Signs and symptoms

Treatment with Taltz resulted in significant improvement in measures of disease activity compared to placebo at week 24 (see Table 910).

Table 910.            Efficacy results in SPIRIT-P1 and SPIRIT-P2 at week 24

[…]

Treatment responses on Taltz were significantly greater than those on placebo as early as week 1 for ACR 20, week 4 for ACR 50 and week 8 for ACR 70 and persisted through week 24; effects were maintained through 3 years for patients who remained in the study.

Figure 34.             ACR 20 response in SPIRIT-P1 over time up to week 24

[…]

In SPIRIT‑P1, 63 patients completed 3 years of Q4W ixekizumab treatment. Among the 107 patients who were randomized to ixekizumab Q4W (NRI analysis in ITT population), 54 patients (50%), 41 patients (38%), 29 patients (27%), and 36 patients (34%) were observed to have ACR20, ACR50, ACR70, and MDA response, respectively, at Week 156.

In SPIRIT‑P2, 70 patients completed 3 years of Q4W ixekizumab treatment. Among the 122 patients who were randomized to ixekizumab Q4W (NRI analysis in ITT population), 56 patients (46%), 39 patients (32%), 24 patients (20%) and 33 (27%) were observed to have ACR20, ACR50, ACR70, and MDA response, respectively, at Week 156.

[…]

Radiographic response

In SPIRIT-P1, inhibition of progression of structural damage was assessed radiographically and expressed as the change in modified total Sharp Score (mTSS) and its components, the Erosion Score (ES) and the Joint Space Narrowing score (JSN) at weeks 24 and 52, compared to baseline. week 24 data are presented in Table 110.

Table 110.            Change in modified Total Sharp Score in SPIRIT-P1

[…]

Radiographic joint damage progression was inhibited by Taltz (Table 110) at week 24, and the percentage of patients with no radiographic joint damage progression (defined as a change from baseline in mTSS of ≤0.5) from randomisation to week 24 was 94.8 % for Taltz Q2W(p < 0.001), 89.0 % for Taltz Q4W(p=0.026), 95.8 % for adalimumab (p < 0.001), all compared to 77.4 % for placebo. At week 52, the mean change from baseline in mTSS was 0.27 for placebo/Taltz Q4W, 0.54 for Taltz Q4W/Taltz Q4W, and 0.32 for adalimumab/Taltz Q4W. The percentage of patients with no radiographic joint damage progression from randomisation to week 52 was 90.9 % for placebo/Taltz Q4W, 85.6 % for Taltz Q4W/Taltz Q4W, and 89.4 % for adalimumab/Taltz Q4W. Patients had no structural progression from baseline (defined as mTSS≤0.5) in the treatment arms as follows: Placebo/Taltz Q4W 81.5% (N=22/27), Taltz Q4W/Taltz Q4W 73.6% (N=53/72), and adalimumab/Taltz Q4W 88.2% (N=30/34).

[…]

Taltz was superior to ADA on the primary study objective: simultaneous achievement of ACR 50 and PASI 100 response at week 24 (Taltz 36.0% vs ADA 27.9%; p=0.036; 95% confidence interval [0.5%, 15.8%]). Taltz also showed non-inferiority (pre-specified margin of -12%) to ADA on ACR 50 (ITT analysis: Taltz 50.5% vs ADA 46.6%; 3.9% difference vs. ADA; 95% confidence interval [-4.3%; 12.1%] ; PPS analysis Taltz: 52.3%, ADA: 53.1%, difference: -0.8% [CI: -10.3%; 8.7%]) and superiority on PASI 100 at week 24 (60.1 % with Taltz vs 46.6% with ADA, p=0.001), which were the major secondary endpoints in the study. At Week 52 a higher proportion of patients treated with Taltz versus ADA simultaneously achieved ACR50 and PASI 100 [39% (111/283) versus 26% (74/283)] and PASI 100 [64% (182/283) versus 41% (117/283)]. Taltz and ADA treatment resulted in similar responses for ACR50 [49.8% (141/283) versus 49.8% (141/283)]. Responses to Taltz were consistent when used as monotherapy or with concomitant use of methotrexate.

Figure 45. Primary endpoint (simultaneous ACR 50 & PASI 100) and major secondary endpoints (ACR 50; PASI 100) response rates week 0 – 24 [ITT population, NRI]**

[…]

Clinical response

In both studies, patients treated with Taltz 80 mg Q2W or 80 mg Q4W demonstrated greater improvements in ASAS40 and ASAS20 responses compared to placebo at week 16 (Table 121). Responses were similar in patients regardless of concomitant therapies. In COAST-W, responses were seen regardless of the number of prior TNF inhibitors.

Table 121.            Efficacy results in COAST-V and COAST-W at week 16

[…]

Figure 56.        Percent of patients achieving ASAS40 responses in COAST-V and COAST-W through week 16, NRI^a

[…]

In COAST-V and COAST-W efficacy was maintained up to week 52 as assessed by the endpoints presented in Table 121, including ASAS20, ASAS40, ASDAS, BASDAI, and ASAS HI response rates.

[…]

Clinical response

Higher proportions of patients treated with Taltz 80 mg Q4W achieved ASAS40 response compared to placebo at week 16 (Table 132). Responses were similar regardless of concomitant therapies.

Table 132.            Efficacy results at week 16 in COAST-X, NRI ^a,b

[…]

Figure 67.             Percent of patients achieving ASAS40 response through week 16 in COAST-X, NRI^a

[…]

Efficacy was maintained up to week 52 as assessed by the endpoints presented in Table 132.

[…]

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 25 April 2016

Date of latest renewal: 17 December 2020

10.       DATE OF REVISION OF THE TEXT

17 December 2020 14 January 2021

                                                                                                                                                                                                                                                                                                                                                                                                                               TA132M

Changes

Added (underline) deleted (strikethrough)

• Table and Figure numbers updated
• Formatting updates made throughout the document

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

[…]

Ixekizumab is a recombinant humanised monoclonal antibody produced in CHO cells by recombinant DNA technology.

[…]

3.         PHARMACEUTICAL FORM

Pre-filled syringe

Solution for injection in pre-filled syringe (injection).

Pre-filled pen

Solution for injection in pre-filled pen.

4.2          Posology and method of administration

This medicinal product Taltz is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which Taltz it is indicated.

[…]

Special populations

Elderly (≥ 65 years)

No dose adjustment is required (see section 5.2).

There is limited information in subjects aged ≥ 75 years.

Renal or hepatic impairment

Taltz has not been studied in these patient populations. No dose recommendations can be made.

Paediatric population

[…]

For instructions on preparation of the medicinal product before administration, see section 6.6.

[…]

4.4          Special warnings and precautions for use

[…]

Taltz should be used with caution in patients with clinically important chronic infection or a history of recurrent infection. Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur.  If an infection develops, monitor patients should be carefully monitored and Taltz discontinued Taltz if the patient is not responding to standard therapy or if the infection becomes serious. Taltz should not be resumed until the infection resolves.

Taltz must not be given to patients with active tuberculosis (TB). Consider aAnti-TB therapy prior to initiation of Taltz in patients with latent TB should be considered.

[…]

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per 80 mg dose, that is to sayi.e., essentially “sodium-free”.

4.5          Interaction with other medicinal products and other forms of interaction

In plaque psoriasis studies, the safety of Taltz in combination with other immunomodulatory agents or phototherapy has not been evaluated.

In population pharmacokinetic analyses, drug clearance of ixekizumab was not affected by concomitant administration of oral corticosteroids, NSAIDs, sulfasalazine, or methotrexate.

Cytochrome P450 Ssubstrates

Results from an drug-drug interaction study in patients with moderate-to-severe psoriasis determined that 12 weeks of administration of ixekizumab with substances drugs metaboliszed by CYP3A4 (i.e., midazolam), CYP2C9 (i.e., warfarin), CYP2C19 (i.e., omeprazole), CYP1A2 (i.e., caffeine) or CYP2D6 (i.e., dextromethorphan) does not have a clinically significant impact on the pharmacokinetics of these substancesdrugs.

4.8          Undesirable effects

Summary of the safety profile

The most frequently reported adverse drug reactions (ADRs) were injection site reactions (15.5 %) and upper respiratory tract infections (16.4 %) (most frequently nasopharyngitis).

Tabulated list of adverse reactions

Adverse reactionsDRs from clinical studies and postmarketing reports (Table 1) are listed by MedDRA system organ class. Within each system organ class, the Aadverse reactionsDRs are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reaction is are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reactionADR is based on the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000).

A total of 8,956 patients have been treated with Taltz in blinded and open-label clinical studies in plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, and other autoimmune conditions. Of these, 6,385 patients were exposed to Taltz for at least one year, cumulatively representing 19,833 adult patient years of exposure and 196 children cumulatively representing 207 patient years of exposure.

In plaque psoriasis in adults a total of 3,119 patients were evaluated in clinical trials (2,328 patients on ixekizumab).

In psoriatic arthritis in adults a total of 678 patients were evaluated in clinical trials (454 patients on ixekizumab).

In axial spondyloarthritis (radiographic and non-radiographic AxSpA) a total of 868 patients were evaluated in clinical trials (574 patients on ixekizumab).

[…]

Description of selected adverse reactions

(Based on adverse reactions data from 4,204 patients with moderate to severe plaque psoriasis [4,729.7 patient years] and 1,117 patients with active psoriatic arthritis [1,050.6 patient years] and 196 patients with paediatric psoriasis [207 patient years] who have received at least 1 dose of ixekizumab.)

5.1          Pharmacodynamic properties

[…]

Clinical efficacy and safety

Adult plaque psoriasis

The efficacy and safety of Taltz were assessed in three randomised, double--blind, placebo--controlled phase III studies in adult patients (N=3,866) with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy (UNCOVER--1, UNCOVER--2, and UNCOVER--3). The efficacy and safety of Taltz were also evaluated versus etanercept (UNCOVER--2 and UNCOVER--3). Patients randomised to Taltz who were sPGA (0,1) responders (static Physicians Global Assessment) at Wweek 12 were re--randomised to receive placebo or Taltz for an additional 48 weeks (UNCOVER--1 and UNCOVER--2); patients randomised to placebo, etanercept or Taltz who were sPGA (0,1) non-responders received Taltz for up to 48 weeks.

Of the 3,866 patients enrolled in these placebo-controlled studies, 64 % of patients had received prior systemic therapy (biologic, conventional systemic or psoralen and ultraviolet A (PUVA)), 43.5 % had received prior phototherapy, 49.3 % had received prior conventional systemic therapy, and 26.4 % had received prior biologic therapy. for the treatment of psoriasis. Of all patients, 14.9 % had received at least one anti--TNF alpha agent, and 8.7 % had received an anti--IL--12/IL--23. 23.4 % of patients had a history of psoriatic arthritis at baseline.

In all three studies, the co-primary endpoints were the proportion of patients who achieved a PASI 75 response (Psoriasis Area and Severity Index) and an sPGA of 0 (“clear”) or 1 (“minimal”) response at Wweek 12 versus placebo. Patients in all treatment groups had a The median baseline PASI score rangeding from 17.4 to 18.3; 48.3 % to 51.2 % of patients had a baseline sPGA score of severe or very severe, and mean baseline itch Numeric Rating Scale (itch NRS) rangeding from 6.3 to 7.1.

Clinical response at 12 weeks

UNCOVER--1 randomisedenrolled 1,296 patients. Patients were randomised (1:1:1) to receive either placebo or Taltz (80 mg every two or four weeks [Q2W or Q4W] following a 160 mg starting dose) for 12 weeks.

[…]

UNCOVER--2 enrolled randomised 1,224 patients. Patients were randomised  (1:2:2:2) to receive either placebo, or Taltz (80 mg every two or four weeks [Q2W or Q4W] following a 160 mg starting dose) or etanercept 50 mg twice weekly for 12 weeks.

[…]

UNCOVER--3 randomised enrolled 1,346 patients. Patients were randomised (1:2:2:2) to receive either placebo, or Taltz (80 mg every two or four weeks [Q2W or Q4W] following a 160 mg starting dose) or etanercept 50 mg twice weekly for 12 weeks.

[…]

Efficacy in Non-Responders to Etanercept: For patients identified as an sPGA (0,1) non--responder to etanercept at wWeek 12 in UNCOVER--2 (N = 200) and who were switched to Taltz 80 mg Q4W after a 4 week washout period, 73 % and 83.5 % of patients were able to achieved sPGA (0,1) and PASI 75, respectively, after 12 weeks of being treatmented with Taltz.

In the 2 clinical studies that included an active comparator (UNCOVER--2 and UNCOVER--3), the rate of serious adverse events was 1.9 % for both etanercept and for Taltz, and the rate of discontinuation due to adverse events was 1.2 % for etanercept and 2.0 % for Taltz. The rate of infections was 21.5 % for etanercept and 26.0 % for Taltz, with the majority of the events mild to moderate in severity. The rate of serious infections was 0.4 % being serious for etanercept and 0.5 % for Taltz.

[…]

Maintenance of Rresponse at wWeek 60

Patients originally randomised to Taltz and who were responders at Week week 12 (i.e., sPGA score of 0,1) in UNCOVER--1 and UNCOVER--2 were re--randomised to an additional 48 weeks of one of the following treatment with regimens: placebo, or Taltz (80 mg every four or twelve weeks [Q4W or Q12W]).

For sPGA (0,1) responders at week 12 re‑randomised to treatment withdrawal (i.e., placebo), the median time to relapse (sPGA ≥ 3) was 164 days in integrated UNCOVER‑1 and UNCOVER‑2 studies. Among these patients, 71.5 % regained at least an sPGA (0,1) response within 12 weeks of restarting treatment with Taltz 80 mg Q4W.

For sPGA (0,1) responders at Week 12 re-randomised to treatment withdrawal (i.e., placebo), the median time to relapse (sPGA ≥ 3) was 164 days in integrated UNCOVER-1 and UNCOVER-2 studies. Among these patients, 71.5 % regained at least an sPGA (0,1) response within 12 weeks of restarting treatment with Taltz 80 mg Q4W.

Significantly greater improvements at Week week 12 from baseline compared to placebo and etanercept were demonstrated in nail psoriasis (as measured by the Nail Psoriasis Severity Index [NAPSI]), in scalp psoriasis (as measured by Psoriasis Scalp Severity Index [PSSI]) and in palmoplantar psoriasis (as measured by Psoriasis Palmoplantar Severity Index [PPASI]) and. These improvements in nail, scalp and palmoplantar psoriasis were maintained at Week week 60 in patients treated with Taltz who were sPGA (0,1) responders at Week week 12.

Quality of Llife/Ppatient--Rreported oOutcomes

At Week week 12 and across studies, Taltz was associated with statistically significant improvement in Health--related Quality of Life as assessed by mean decrease ranges from baseline in the Dermatology Life Quality Index (DLQI) (Taltz 80 mg Q2W from --10.2 to --11.1, Taltz 80 mg Q4W from --9.4 to --10.7, etanercept from --7.7 to --8.0 and placebo --1.0 to --2.0). A significantly greater proportion of patients treated with Taltz achieved a DLQI 0 or 1. Across studies, Taltz was associated with statistically significant improvement of itching severity assessed by the Itch NRS score. A a significantly greater proportion of patients treated with Taltz achieved a reduction of Itch NRS ≥ 4 points at week 12 (84.6 % for Taltz Q2W, 79.2 % for Taltz Q4W and 16.5 % for placebo) and the benefit was sustained over time up to Week week 60 in patients treated with Taltz who were sPGA (0 or 1) responders at Week week 12. There was not any evidence of worsening of depression up to 60  weeks treatment with Taltz as assessed by the Quick Inventory of Depressive Symptomatology Self Report.

Postmarketing pPhase 3b, direct comparative study
Efficacy and safety of ixekizumab was also investigated iIn a double-blind study compared to ustekinumab with ixekizumab was being superior against ustekinumab on the primary study objective (PASI 90 response at week 12, (Table 6). Onset of response was superior on PASI 75 as early as week 2 (p < 0.001) and on PASI 90 and PASI 100 by week 4 (p < 0.001). Superiority of ixekizumab versus ustekinumab was also demonstrated in the subgroups stratified by weight.

[…]

Psoriatic arthritis

The safety and efficacy of Taltz wasere assessed in two randomised, double-blind, placebo-controlled phase III studies in 780  patients with active psoriatic arthritis (≥ 3 swollen and ≥ 3 tender joints). Patients in these studies had a diagnosis of psoriatic arthritis (Classification Criteria for Psoriatic Arthritis [CASPAR] criteria) for a median of 5.33  years and. Randomised patients also had current plaque psoriasis skin lesions (94.0 %) or a documented history of plaque psoriasis, with 12.1 % of patients with moderate to severe plaque psoriasis at baseline. Over 58.9 % and 22.3 % of the psoriatic arthritis patients had enthesitis and dactylitis at baseline, respectively. For Primary endpoint of both studies was, the primary endpoint was American College of Rheumatology (ACR) 20 response at Wweek  24.

In Psoriatic Arthritis Study 1 (SPIRIT--P1), patients naive to biologic therapy with active psoriatic arthritis were randomised to subcutaneous injections of placebo, adalimumab 40 mg once every 2 weeks (active control reference arm), Taltz 80 mg once every 2 weeks (Q2W), or 80 mg once every 4 weeks (Q4W). Both Taltz regimens included a 160 mg starting dose. 85.3 % of patients in this study had received prior treatment with ≥ 1 cDMARD. 53 % of patients had concomitant use of MTX at a mean weekly dose of 15.8  mg.  67 % of patients who had concomitant use of MTX had a dose of 15 mg or greater. Patients in all treatment groups with an inadequate response at week  16 received rescue therapy (modification to background therapy). Patients on Taltz Q2W or Q4W remained on their originally assigned dose of Taltz. Patients receiving adalimumab or placebo were re-randomised 1:1 to Taltz Q2W or Q4W at week 16 or 24 based on responder status.

Psoriatic Arthritis Study 2 (SPIRIT-P2) enrolled patients who were previously treated with an anti--TNF  agent and discontinued the anti-TNF agent for either lack of efficacy or intolerance (anti--TNF--IR  patients). Patients were randomised to subcutaneous injections of placebo, Taltz 80 mg once every 2 weeks (Q2W), or 80 mg once every 4 weeks (Q4W).  Both Taltz regimens included a 160 mg starting dose. 56 % and 35 % of patients were inadequate responders to 1 anti--TNF or 2 anti-TNF, respectively.  SPIRIT--P2 evaluated 363  patients, of whom 41 % had concomitant use of MTX at a mean weekly dose of 16.1  mg. 73.2 % of patients who had concomitant use of MTX had a dose of 15  mg or greater. Patients in all treatment groups with an inadequate response at week  16 received rescue therapy (modification to background therapy). Patients in Taltz Q2W or Q4W remained on their originally assigned dose of Taltz. Patients receiving placebo were re-randomised 1:1 to Taltz Q2W or Q4W at week 16 or 24 based on responder status.

[…]

Axial Spondyloarthritisspondyloarthritis

The safety and efficacy of Taltz wasere assessed in a total of 960 adult patients with axial spondyloarthritis in three randomised placebo-controlled studies (two in radiographic axial spondyloarthritis, and one in non-radiographic axial spondyloarthritis).

Radiographic Axial axial Spondyloarthritisspondyloarthritis

The safety and efficacy of Taltz wasere assessed in a total of 657  patients in two randomised, double‑-blind, placebo--controlled studies (COAST--V and COAST--W) in adult patients ≥18 years of age, with axial spondyloarthritis. Patients who had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 and total back pain ≥4 on a numeric rating scale despite non-steroidal anti--inflammatory drug (NSAID) therapy. Across both studies at baseline, patients had symptoms of axial spondyloarthritis for a mean of 17 years (median of 16 years). At baseline, approximately 32% of the patients were on a concomitant cDMARD.

COAST--V evaluated 341 biologic-naive patients, who were treated with either Taltz 80 mg or 160 mg at Week week 0 followed by 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), adalimumab 40 mg every 2 weeks, or with placebo. Patients receiving placebo were re-randomised at Week week 16 to receive Taltz (160 mg starting dose, followed by 80 mg Q2W or Q4W). Patients receiving adalimumab were re‑randomised at Week week 16 to receive Taltz (80 mg Q2W or Q4W).

COAST--W evaluated 316 patients who had prior experience with 1 or 2 TNF-inhibitors (90% were inadequate responders and 10% were intolerant to TNF inhibitors). All patients were treated with Taltz 80 or 160 mg at Week week 0 followed by 80 mg Q2W or Q4W, or with placebo. Patients receiving placebo were re-randomised at Week week 16 to receive Taltz (160 mg initial dose, followed by 80 mg Q2W or Q4W).

The primary endpoint in both studies was the percentage of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response at Week week 16.

Clinical Responseresponse

In both studies, patients treated with Taltz 80 mg Q2W or 80 mg Q4W demonstrated greater improvements in ASAS40 and ASAS20 responses compared to placebo at Week week 16 (Table 11). Responses were similar in patients regardless of concomitant therapies. In COAST--W, responses were seen regardless of the number of prior TNF inhibitors.

[…]

The percent of patients achieving an ASAS40 response by visit in COAST-V and COAST-W is shown in Figure 5.

[…]

Non-radiographic Axial axial Spondyloarthritisspondyloarthritis

The efficacy and safety of Taltz wasere assessed in a randomised, double-blind, study with a 52‑week placebo-controlled period (COAST-X) in 303 adult patients ≥18 years of age with active axial spondyloarthritis for at least 3 months. Patients must have had objective signs of inflammation indicated by elevated C--reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI), and no definitive radiographic evidence of structural damage on sacroiliac joints. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, and spinal pain ≥4 on a 0 to 10 Numerical Rating Scale (NRS), despite non-steroidal anti-inflammatory drug (NSAID) therapy. Patients were treated with either Taltz 80 mg or 160 mg at Week week 0, followed by 80 mg every 2 weeks (Q2W) or 80 mg every 4 weeks (Q4W) or with placebo. Dose adjustment and/or initiation of concomitant medications (NSAIDs, cDMARDs, corticosteroids, analgesics) were permitted starting at Week week 16.

[…]

The percent of patients achieving ASAS40 response by visit is shown in Figure 6.

[…]

5.3          Preclinical safety data

Non-clinical data from cynomolgus monkeys revealed no special hazards for humans based on repeat-dose toxicity studies, safety pharmacology evaluations, and reproductive and developmental toxicity studies.

[…]

6.6          Special precautions for disposal and other handling

[…]

Ixekizumab doses of 40 mg must be prepared and administered by a qualified healthcare professional. Use only the Taltz 80 mg solution for injection in /1 ml pre-filled syringe when preparing the prescribed 40 mg paediatric doses.

[…]

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 25 April 2016

Date of latest renewal:

10.       DATE OF REVISION OF THE TEXT

26 June 17 December 2020

TA112M

Changes

Added (underline) deleted (strikethrough)

Formatting changes throughout the document

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

1. What Taltz is and what it is used for

Taltz contains the active substance ixekizumab.

Taltz is intended for the treatment of the inflammatory diseases described below:

• Plaque psoriasis in adults
• Plaque psoriasis in children from the age of 6 and with a body weight of at least 25 kg and in adolescents
• Psoriatic arthritis in adults
• Radiographic Axial Spondyloarthritis in adults
• Non-radiographic Axial Spondyloarthritis in adults

[…]

Psoriatic arthritis

Taltz is used to treat a condition called “psoriatic arthritis” in adults, an inflammatory disease of the joints, often accompanied by psoriasis. If you have psoriatic arthritis you will first be given other medicines. If you do not respond well enough to these medicines or in case of intolerance, you will be given Taltz to reduce the signs and symptoms of the disease. Taltz can be used alone or with another medicine named methotrexate.

2. What you need to know before you use Taltz

[…]

Children and adolescents

Taltz is not recommendedDo not use this medicine for the treatment of plaque psoriasis in children under 6 years of age because it has not been studied in this age group.

Taltz is not recommendedDo not use this medicine for the treatment of psoriatic arthritis in children and adolescents under 18 years of age because it has not been studied in this age group.

Other medicines and Taltz

Tell your doctor, pharmacist or nurse

• if you are using, have recently used or might use any other medicinesmedicine.
• if you have recently had or are due to have a vaccination. You should not be given certain types of vaccines while using Taltz.

[…]

If you are breast‑-feeding or are planning to breast-feed, talk to your doctor before using this medicine. You and your doctor should decide if you will can breast-‑feed or use Taltz. You should not do both.

[…]

Taltz contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per 80 mg dose, i.e.,that is to say essentially “sodium-‑free”.

3. How to use Taltz

Always use this medicine exactly as your doctor or nurse has told you. Check with your doctor, nurse or pharmacist if you are not sure how to use this medicine.

4. Possible side effects

[…]

Other side effects that have been reported:

Some side effects are vVeryvery common (may affect more than 1 in 10 people):

• upper respiratory tract infections with symptoms such as sore throat and stuffy nose.
• injection site reactions (e.g. red skin, pain).

Some side effects are cCommoncommon (may affect up to 1 in 10 people):

• nausea.
• fungal infections such as athlete’s foot.
• pain in the back of the throat.
• cold sores of mouth, skin and mucous membranes (herpes simplex, mucocutaneous)

Some side effects are uUncommonuncommon (may affect up to 1 in 100 people):

[…]

6. Contents of the pack and other information

This leaflet was last revised in June December 2020

• Table and Figure numbers updated
• Formatting updates made throughout the document

4.1              Therapeutic indications   

[…]

Paediatric plaque psoriasis

Taltz is indicated for the treatment of moderate to severe plaque psoriasis in children from the age of 6 years and with a body weight of at least 25 kg and adolescents who are candidates for systemic therapy.

 […]

4.2              Posology and method of administration

 Plaque psoriasis in adults

The recommended dose is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg (one injection) at Weeks 2, 4, 6, 8, 10, and 12, then maintenance dosing of 80 mg (one injection) every 4 weeks (Q4W).

 Paediatric plaque psoriasis (age 6 years and above)

Efficacy and safety data is not available in children below the age of 6 years (see section 5.1). Available data do not support a posology below a body weight of 25 kg.

The recommended dose given by subcutaneous injection in children is based on the following weight categories:

For children prescribed 80 mg, Taltz can be used directly from the prefilled syringe.

For instructions on preparation of Taltz 40 mg, see section 6.6. Doses less than 80 mg must be prepared by a healthcare professional.

Taltz is not recommended for use in children with a body weight below 25 kg. Paediatric body weights must be recorded and regularly re-checked prior to dosing.

 […]

For all indications (plaque psoriasis in adults and children, psoriatic arthritis, axial spondyloarthritis) consideration should be given to discontinuing treatment in patients who have shown no response after 16 to 20 weeks of treatment.  […]

Paediatric plaque psoriasis (below a body weight of 25 kg and below the age of 6 years)

There is no relevant use of Taltz in children below a body weight of 25 kg and below the age of 6 years in the treatment of moderate to severe plaque psoriasis.

Paediatric psoriatic arthritis

The safety and efficacy of Taltz in children and adolescents aged 2 to less than 18 years in the treatment of psoriatic arthritis (a category of juvenile idiopathic arthritis) have not yet been established. No data are available. There is no relevant use of Taltz in children below 2 years for the indication of psoriatic arthritis.

[…]

However, the physician should ensure appropriate follow-up of patients. Comprehensive instructions for administration are given in the package leaflet and the user manual.

Doses less than 80 mg which require dose preparation should only be administered by a healthcare professional.

4.4              Special warnings and precautions for use

Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis)

Cases of new or exacerbations of inflammatory bowel diseaseCrohn’s disease and ulcerative colitis have been reported. with ixekizumab (see section 4.8). Ixekizumab is not recommended inCaution should be exercised when prescribing Taltz to  patients with inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, and patients should be monitored closely. If a patient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation of pre-existing inflammatory bowel disease, ixekizumab should be discontinued and appropriate medical management should be initiated.

4.8              Undesirable effects

[…]

A total of 8,956 patients have been treated with Taltz in blinded and open-label clinical studies in plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, and other autoimmune conditions. Of these, 6,385 patients were exposed to Taltz for at least one year, cumulatively representing 19,833 patient years of exposure and 196 children cumulatively representing 207 patient years of exposure.

In plaque psoriasis in adults a total of 3,119 patients were evaluated in clinical trials (2,328 patients on ixekizumab).

In psoriatic arthritis in adults a total of 678 patients were evaluated in clinical trials (454 patients on ixekizumab).

[…]

Table 1.    List of adverse reactions in clinical studies  and postmarketing reports

Description of selected adverse reactions

(Based on adverse reactions data from 4,204 patients with moderate to severe plaque psoriasis [4,729.7 patient years] and 1,117 patients with active psoriatic arthritis [1,050.6 patient years] and 196 patients with paediatric psoriasis [207 patient years] who have received at least 1 dose of ixekizumab.)

[…]

Injection site reactions

[…]

In the adult plaque psoriasis studies, injection site reactions were more common in subjects with a body weight […]

Infections

In the placebo-controlled period of the phase III clinical studies in plaque psoriasis in adults, […]

Immunogenicity

Approximately 9–17 % of adult plaque psoriasis patients treated with Taltz at the recommended dosing regimen developed anti-drug antibodies, […]

In paediatric psoriasis patients treated with Taltz at the recommended dosing regimen up to 12 weeks, 21 patients (18%) developed anti-drug antibodies, approximately half were low titer and 5 patients (4%) had confirmed neutralizing antibodies associated with low drug concentrations. There was no association with clinical response or adverse events.

[…]

Paediatric population

The safety profile observed in children with plaque psoriasis treated with Taltz every 4 weeks is consistent with the safety profile in adult patients with plaque psoriasis with the exception of the frequencies of conjunctivitis, influenza, and urticaria which were common. Inflammatory bowel disease was also more frequent in paediatric patients, although it was still uncommon. In the paediatric clinical study, Crohn’s disease occurred in 0.9% of patients in the Taltz group and 0% of patients in the placebo group during the 12‑week, placebo-controlled period. Crohn’s disease occurred in a total of 4 Taltz treated subjects (2.0%) during the combined placebo-controlled and maintenance periods of the paediatric clinical study. […]

5.1              Pharmacodynamic properties

[…]

Adult plaque psoriasis

[…]

Paediatric plaque psoriasis

A randomized, double-blind, multicenter, placebo-controlled trial (IXORA-Peds) enrolled 201 children 6 to less than 18 years of age, with moderate to severe plaque psoriasis (as defined by a sPGA score ≥3, involving ≥10% of the body surface area, and a PASI score ≥12) who were candidates for phototherapy or systemic therapy, or were inadequately controlled on topical therapy.

Patients were randomized to placebo (n=56), etanercept (n=30) or Taltz (n=115) with dosing stratified by weight:

<25 kg: 40 mg at Week 0 followed by 20 mg Q4W (n=4)

25 kg to 50 kg: 80 mg at Week 0 followed by 40 mg Q4W (n=50)

>50 kg: 160 mg at Week 0 followed by 80 mg Q4W (n=147)

Patients randomized to etanercept (patients with severe psoriasis) received 0.8 mg/kg, not exceeding 50 mg per dose, every week from Week 0 through Week 11.
Response to treatment was assessed after 12 weeks of therapy and was defined by the proportion of patients who achieved the co‑primary endpoint of an sPGA score of “0” (clear) or “1” (almost clear) with at least a 2 point improvement from baseline and the proportion of patients that achieved a reduction in PASI score of at least 75% (PASI 75) from baseline.

Other evaluated outcomes at Week 12 included the proportion of patients who achieved PASI 90, PASI 100, sPGA of “0” and an improvement of itch severity as measured by a reduction of at least 4 points on an 11‑point itch Numeric Rating Scale.

Patients had a median baseline PASI of 17 score ranging from 12‑49. Baseline sPGA score was severe or very severe in 49%. Of all patients, 22% had received prior phototherapy and 32% had received prior conventional systemic therapy for the treatment of psoriasis.

25% of patients (n=43) were below 12 years (14% of patients [n=24] were 6-9 years and 11% of patients [n=19] were 10-11 years); 75% (n=128) were 12 years or above.

The clinical response data are presented in Table 8.

Table 8.     Efficacy Results in Pediatric Patients with Plaque Psoriasis, NRI

Abbreviations: N = Number of patients in the intent-to-treat population; NRI = Non-Responder Imputation.

a    At Week 0, subjects received 160 mg, 80 mg, or 40 mg of Taltz, followed by 80 mg, 40 mg, or 20 mg every 4 weeks, depending on weight category, for 12 weeks.

b    Comparisons to etanercept were performed within the sub-population of patients outside of US and Canada with severe Ps (N for Taltz = 38).

c    Co-primary endpoints.

d    Results at Week 12.

e    Itch NRS (≥4 improvement) in patients with baseline Itch NRS ≥4. The number of ITT patients with baseline Itch NRS Score ≥4 are as follows: Taltz, n = 83; PBO, n = 40.

f p<0.001

Figure 2. Percent of Patients Achieving PASI 75 in Pediatric Psoriasis Through Week 12

Patients in the ixekizumab treatment group had clinically meaningful higher CDLQI/DLQI (0,1) responses at Week 12 (NRI) compared with placebo. The difference between treatment groups was apparent from as early as Week 4.

There were greater improvements at Week 12 from baseline compared to placebo in nail psoriasis (as measured by the Nail Psoriasis Severity Index [NAPSI=0: Taltz 18% (6/34), placebo 0% (0/12)]), in scalp psoriasis (as measured by Psoriasis Scalp Severity Index [PSSI=0: Taltz 69% (70/102), placebo 16% (8/50)]) and in palmoplantar psoriasis (as measured by Psoriasis Palmoplantar Severity Index [PPASI 75: Taltz 53% (9/17), placebo 11% (1/9)]).

[…]

Paediatric Population

Paediatric psoriasis patients (age 6 to less than 18 years) were administered ixekizumab at the recommended paediatric dosing regimen for 12 weeks. Patients weighing >50 kg and 25 to 50 kg had a mean ±SD steady-state trough concentration of 3.8 ±2.2 µg/ml and 3.9 ±2.4 µg/ml, respectively, at Week 12.

6.6              Special precautions for disposal and other handling

[…]

 40 mg preparation of ixekizumab for children 25-50 kg body weight

Ixekizumab doses of 40 mg must be prepared and administered by a qualified healthcare professional. Use only the Taltz 80 mg/1 ml prefilled syringe when preparing the prescribed 40 mg paediatric doses.

1. Expel the entire contents of the prefilled syringe into a sterile, clear glass vial. DO NOT shake or swirl the vial.
2. Use a 0.5 mL or 1 mL disposable syringe and sterile needle to withdraw the prescribed dose (0.5 ml for 40 mg) from the vial.
3. Change the needle and use a 27‑gauge, sterile needle to inject the patient. Discard any unused ixekizumab in the vial.
   The prepared ixekizumab must be administered within 4 hours of puncturing the sterile vial at room temperature.

10.       DATE OF REVISION OF THE TEXT 

                02 June 202026 June 2020

1. What Taltz is and what it is used for 

Taltz is intended for the treatment of the inflammatory diseases described below:

• Plaque psoriasis in adults
• Plaque psoriasis in children from the age of 6 and with a body weight of at least 25 kg and in adolescents
• Psoriatic arthritis in adults
  […] 

Plaque psoriasis

Taltz is used to treat a skin condition called “plaque psoriasis” in adults and in children from the age of 6 years and with a body weight of at least 25 kg and in adolescents with moderate to severe disease. […]

1. What you need to know before you use Taltz
    

Warnings and precautions

• if you have an inflammatory disease affecting the gut nameda chronic inflammatory disease of your digestive tract named Crohn’s disease.
• if you have an inflammation of the large intestine nameda chronic inflammation of the large intestine named ulcerative colitis.
   
  Inflammatory bowel disease (Crohn's disease or ulcerative colitis)
  Stop using Taltz and tell your doctor or seek medical help immediately if you notice abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (any signs of bowel problems).
   

Children and adolescents

Taltz is not recommended for the treatment of plaque psoriasis in children under 6 years of age because it has not been studied in this age group.

Taltz is not recommended for the treatment of psoriatic arthritis in children and adolescents under 18 years of age because it has not been studied in this age group.

1. How to use Taltz
    

For use in children with a body weight of 25-50 kg ixekizumab doses of 40 mg must be prepared and administered by a qualified healthcare professional.

Use the Taltz 80 mg pre-filled pen only in those children that require a dose of 80 mg and do not require dose preparation.

Plaque psoriasis in adults

[…]

Plaque psoriasis in children (age 6 years and above and at least 25 kg body weight) and in adolescents

The recommended dose given by subcutaneous injection in children is based on the following weight categories:

Ixekizumab doses of 40 mg must be prepared and administered by a qualified healthcare professional using the commercial Taltz 80 mg/1 ml prefilled syringe.
Use the Taltz 80 mg pre-filled pen only in those children that require a dose of 80 mg. Do not use the Taltz 80 mg pre-filled pen for the preparation of the 40 mg dose.

Taltz is not recommended for use in children with a body weight below 25 kg.

4.             Possible side effects

Some side effects are uncommon (may affect up to 1 in 100 people):

• abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (signs of bowel problems)

6.             Contents of the pack and other information

This leaflet was last revised in June2020.

1. What Taltz is and what it is used for

Taltz is intended for the treatment of the inflammatory diseases described below:

• Plaque psoriasis
• Psoriatic arthritis
• Radiographic Axial Spondyloarthritis
• Non-radiographic Axial Spondyloarthritis

Ixekizumab belongs to a group of medicines called interleukin (IL) inhibitors. This medicine works by blocking neutralising the activity of a protein called IL-17A, which promotes psoriasis and inflammatory disease of the joints and the spinepsoriatic arthritis.

Psoriatic arthritis

Taltz is used to treat a condition called “psoriatic arthritis” in adults, an inflammatory disease of the joints, often accompanied by psoriasis.

Axial Spondyloarthritis

Taltz is used to treat adults with an inflammatory disease primarily affecting the spine which causes inflammation of the spinal joints, called Axial Spondyloarthritis. If the condition is visible using X‑rays, it is referred to as “radiographic Axial Spondyloarthritis”; if it occurs in patients with no visible signs on X-rays, it is referred to as “non-radiographic Axial Spondyloarthritis”. If you have Axial Spondyloarthritis you will first be given other medicines. If you do not respond well enough to these medicines, you will be given Taltz to reduce the signs and symptoms of the disease, reduce inflammation and improve your physical function.

1. What you need to know before you use Taltz
    

Warnings and precautions

Talk to your doctor, nurse or pharmacist before using Taltz:

• if you have a chronic inflammatory disease of your digestive tract named Crohn’s disease.
• if you have a chronic inflammation of the large intestine named ulcerative colitis.

1. How to use Taltz

Use a reminder method such as notes in a calendar or diary to help you remember your next dose so that you avoid missing or repeating doses.

Taltz is for long-term treatment. Your doctor or nurse will regularly monitor your condition to check that the treatment is having the desired effect.

How much Taltz is given and for how long

Your doctor will explain to you decide how much Taltz you need and for how long.

Plaque psoriasis

• The first dose is 160 mg (2 pens with 80 mg each) (two 80 mg injections) by subcutaneous injection. This may be given by your doctor or nurse.
• After the first dose, you will use an 80 mg dose (1 penone injection) at Weeks 2, 4, 6, 8, 10, and 12. From Week 12, you will use an 80 mg dose (1 penone injection) every 4 weeks.
   

Psoriatic arthritis

For psoriatic arthritis patients who also have moderate to severe plaque psoriasis:

• The first dose is 160 mg (2 pens with 80 mg each) (two 80 mg injections) by subcutaneous injection. This may be given by your doctor or nurse.
• After the first dose, you will use an 80 mg dose (1 penone injection) at Weeks 2, 4, 6, 8, 10, and 12. From Week 12, you will use an 80 mg dose (1 penone injection) every 4 weeks.

For other psoriatic arthritis patients:

• The first dose is 160 mg (2 pens with 80 mg each)(two 80 mg injections) by subcutaneous injection. This may be given by your doctor or nurse.
• After the first dose you will use an 80 mg dose (1 penone injection) every 4 weeks.

Axial Spondyloarthritis

The recommended dose is 160 mg (2 pens with 80 mg each) by subcutaneous injection at Week 0, followed by 80 mg (1 pen) every 4 weeks.

Use a reminder method such as notes in a calendar or diary to help you remember your next dose so that you avoid missing or repeating doses.

Taltz is for long-term treatment. Your doctor or nurse will regularly monitor your condition to check that the treatment is having the desired effect.

1. Possible side effects

Some side effects are very common (may affect more than 1 in 10 people):

• upper respiratory tract infections with symptoms such as sore throat and stuffy nose (nasopharyngitis).
   
  Some side effects are common (may affect up to 1 in 10 people):
• nausea (feeling sick).
• tinea (fungal) infections such as athlete’s foot.
• cCold sores of mouth, skin and mucous membranes (herpes simplex, mucocutaneous)
   
  Some side effects are uncommon (may affect up to 1 in 100 people):
• eEczema.
• rRash.
• rRapid swelling of the tissues of the neck, face, mouth or throat (angioedema).
   
  Reporting of side effects

… via Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, website: www.hpra.ie, e-mail: medsafety@hpra.ie, …

1. How to store Taltz

Store in a refrigerator (2 °C to– 8 °C). Do not freeze. Do not push to the back panel of the fridge.

Do not throw away any medicines via wastewater or household waste.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

This leaflet was last revised in January 2018June 2020.

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Various minor grammar and format updates

4.1         Therapeutic indications

Axial spondyloarthritis

Ankylosing spondylitis (radiographic axial spondyloarthritis)
Taltz is indicated for the treatment of adult patients with active ankylosing spondylitis who have responded inadequately to conventional therapy.

Non-radiographic axial spondyloarthritis
Taltz is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs).

4.2         Posology and method of administration

Axial spondyloarthritis (radiographic and non-radiographic)

The recommended dose is 160 mg (two 80 mg injections) by subcutaneous injection at Week 0, followed by 80 mg every 4 weeks (see section 5.1 for further information).

For all indications (plaque psoriasis, psoriatic arthritis, axial spondyloarthritis) cConsideration […].

Paediatric population

The safety and efficacy of Taltz in children below the age of and adolescents aged 6 to 18 years in the treatment of moderate to severe plaque psoriasis have not yet been established. No data are available.

There is no relevant use of Taltz in children below the age of 6 years in the treatment of moderate to severe plaque psoriasis.

The safety and efficacy of Taltz in children and adolescents aged 2 to less than 18 years in the treatment of psoriatic arthritis (a category of juvenile idiopathic arthritis) have not yet been established. No data are available. There is no relevant use of Taltz in children below 2 years for the indication of psoriatic arthritis.

4.4         Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Taltz should be used with caution in patients with clinically important chronic infection or a history of recurrent infection. Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. […]

4.5         Interaction with other medicinal products and other forms of interaction

In population pharmacokinetic analyses, No interaction was seen when Taltz was administered concomitantly with methotrexate (MTX) and/or corticosteroids in patients with psoriatic arthritis.

In population pharmacokinetic analyses in patients with axial spondyloarthritis, drug clearance of ixekizumab was not affected by concomitant administration of oral corticosteroids, NSAIDs, sulfasalazine, or methotrexate.

No interaction was seen when Taltz was administered concomitantly with methotrexate (MTX) and/or corticosteroids in patients with psoriatic arthritis.

4.8         Undesirable effects

Summary of the safety profile

The most frequently reported adverse drug reactions (ADRs) were injection site reactions (15.5 %) and upper respiratory tract infections (16.4 %) (most frequently nasopharyngitis).

Tabulated list of adverse reactions

[…]

A total of 7,339 patients have been treated with Taltz in blinded and open-label clinical studies in plaque psoriasis, psoriatic arthritis, and other autoimmune conditions. Of these, 4,500 patients were exposed to Taltz for at least one year, cumulatively representing 13,645.6 patient years of exposure.

In plaque psoriasis, three placebo-controlled phase III studies were integrated to evaluate the safety of Taltz in comparison to placebo up to 12 weeks after treatment initiation. A total of 3,119 patients were evaluated (1,161 patients on 80 mg every 4 weeks (Q4W), 1,167 patients on 80 mg every 2 weeks (Q2W) and 791 patients on placebo).

In psoriatic arthritis, two placebo-controlled phase III studies were integrated to evaluate the safety of Taltz in comparison to placebo up to 24 weeks after treatment initiation. A total of 678 patients were evaluated (229 patients on 80 mg every 4 weeks (Q4W), 225 patients on 80 mg every 2 weeks (Q2W) and 224 patients on placebo). The safety profile observed in patients with psoriatic arthritis treated with Taltz is consistent with the safety profile in plaque psoriasis with the exception of the frequencies of the adverse reactions of influenza and conjunctivitis which were common in patients with psoriatic arthritis

A total of 8,953 patients have been treated with Taltz in blinded and open-label clinical studies in plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, and other autoimmune conditions. Of these, 6,343 patients were exposed to Taltz for at least one year, cumulatively representing 19,772.1 patient years of exposure.

In plaque psoriasis a total of 3,119 patients were evaluated in clinical trials (2,328 patients on ixekizumab).

In psoriatic arthritis a total of 678 patients were evaluated in clinical trials (454 patients on ixekizumab).

In axial spondyloarthritis (radiographic and non-radiographic axSpA) a total of 868 patients were evaluated in clinical trials (574 patients on ixekizumab).

Table 1.               List of adverse reactions in clinical studies and postmarketing reports

[updated table references]

Description of selected adverse reactions

(Based on adverse reactions data from 4,204 patients with moderate to severe plaque psoriasis [4,729.7 patient years] and 1,117 patients with active psoriatic arthritis [1,050.6 patient years] who have received at least 1 dose of ixekizumab.)

Injection site reactions

The most frequent injection site reactions observed were erythema and pain. These reactions were predominantly mild to moderate in severity and did not lead to discontinuation of Taltz.

In the plaque psoriasis studies, injection site reactions were more common in subjects with a body weight < 60 kg compared with the group with a body weight ≥ 60 kg (25 % vs. 14 % for the combined Q2W and Q4W groups). In the psoriatic arthritis studies, injection site reactions were more common in subjects with a body weight < 100 kg compared with the group with a body weight ≥ 100 kg (24 % vs. 13 % for the combined Q2W and Q4W groups). In the axial spondyloarthritis studies, injection site reactions were similar in subjects with a body weight < 100 kg compared with the group with a body weight ≥ 100 kg (14 % vs. 9 % for the combined Q2W and Q4W groups). The increased frequency of injection site reactions in the combined Q2W and Q4W groups did not result in an increase in discontinuations in either the plaque psoriasis, or the psoriatic arthritis or the axial spondyloarthritis studies.

[…]

In radiographic axial spondyloarthritis patients treated with Taltz at the recommended dosing regimen up to 16 weeks, 5.2% developed anti-drug antibodies, the majority of which were low titer, and 1.5% (3 patients) had neutralising antibodies (NAb). In these 3 patients, NAb-positive samples had low ixekizumab concentrations and none of these patients achieved an ASAS40 response. In non‑radiographic axial spondyloarthritis patients treated with Taltz at the recommended dosing regimen for up to 52 weeks, 8.9% developed anti-drug antibodies, all of which were low titer; no patient had neutralising antibodies; and no apparent association between the presence of anti‑drug antibodies and drug concentration, efficacy, or safety was observed.

Across all indications, aAn […]

5.1         Pharmacodynamic properties

Mechanism of action

[…] psoriatic arthritis and axial spondyloarthritis by driving inflammation leading to erosive bone damage and pathological new bone formation. […]

Table 3. Efficacy results at Week 12 in UNCOVER-2

[updated table references]

Axial Spondyloarthritis

The safety and efficacy of Taltz were assessed in a total of 960 adult patients with axial spondyloarthritis in three randomised placebo-controlled studies (two in radiographic axial spondyloarthritis, one in non-radiographic axial spondyloarthritis).

Radiographic Axial Spondyloarthritis

The safety and efficacy of Taltz were assessed in a total of 657 patients in two randomised, double‑blind, placebo-controlled studies (COAST-V and COAST-W) in adult patients ≥18 years of age, with axial spondyloarthritis. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 and total back pain ≥4 on a numeric rating scale despite non-steroidal anti-inflammatory drug (NSAID) therapy. Across both studies at baseline, patients had symptoms of axial spondyloarthritis for a mean of 17 years (median of 16 years). At baseline, approximately 32% of the patients were on a concomitant cDMARD.

COAST-V evaluated 341 biologic-naive patients, who were treated with either Taltz 80 mg or 160 mg at Week 0 followed by 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), adalimumab 40 mg every 2 weeks, or with placebo. Patients receiving placebo were re-randomised at Week 16 to receive Taltz (160 mg starting dose, followed by 80 mg Q2W or Q4W). Patients receiving adalimumab were re‑randomised at Week 16 to receive Taltz (80 mg Q2W or Q4W).

COAST-W evaluated 316 patients who had prior experience with 1 or 2 TNF-inhibitors (90% were inadequate responders and 10% were intolerant to TNF inhibitors). All patients were treated with Taltz 80 or 160 mg at Week 0 followed by 80 mg Q2W or Q4W, or with placebo. Patients receiving placebo were re-randomised at Week 16 to receive Taltz (160 mg initial dose, followed by 80 mg Q2W or Q4W).

The primary endpoint in both studies was the percentage of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response at Week 16.

Clinical Response

In both studies, patients treated with Taltz 80 mg Q2W or 80 mg Q4W demonstrated greater improvements in ASAS40 and ASAS20 responses compared to placebo at Week 16 (Table 10). Responses were similar in patients regardless of concomitant therapies. In COAST-W, responses were seen regardless of the number of prior TNF inhibitors.

Table 10.             Efficacy results in COAST-V and COAST-W at Week 16