Taltz 80 mg solution for injection in pre-filled syringe

  • Name:

    Taltz 80 mg solution for injection in pre-filled syringe

  • Company:
    info
  • Active Ingredients:

    Ixekizumab

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 03/07/20

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Summary of Product Characteristics last updated on medicines.ie: 3/7/2020
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.

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Eli Lilly and Company (Ireland) Limited

Eli Lilly and Company (Ireland) Limited

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When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 3 July 2020 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text
  • Improved presentation of SmPC

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

  • 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:

 

Children’s Body Weight

Recommended Starting Dose (Week 0)

Recommended Dose every 4 weeks (Q4W) thereafter

Greater than 50 kg

160 mg (two 80 mg injections)

80 mg

25 to 50 kg

80 mg

40 mg

 

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

 

Gastrointestinal disorders

Common

Nausea

Uncommon

Inflammatory bowel disease

 

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

Endpoints

Taltza

(N=115)

n (%)

Placebo

(N=56)

n (%)

Difference vs placebo (95% CI)

Etanerceptb

(N=30)

n (%)

Difference vs etanercept (95% CI)b

sPGA “0” (clear) or “1” (almost clear)c

 

 

 

 

 

week 4

55 (48)

4 (7)

40.7 (29.3, 52.0)f

0(0)

36.8 (21.5, 52.2)

Week 12c

93 (81)

6 (11)

70.2 (59.3, 81.0)f

16 (53)

23.0 (0.6, 45.4)

sPGA “0” (clear) d

60 (52)

1 (2)

50.4 (40.6, 60.2)f

5 (17)

46.5 (26.2, 66.8)

PASI 75c

 

 

 

 

 

week 4

62 (54)

5 (9)

45.0 (33.2, 56.8)f

3 (10)

34.7 (15.6, 53.8)

week 12

102 (89)

14 (25)

63.7 (51.0, 76.4)f

19 (63)

20.9 (0.1, 41.7)

PASI 90d

90 (78)

3 (5)

72.9 (63.3, 82.5)f

12 (40)

36.3 (14.2, 58.5)

PASI 100d

57 (50)

1 (2)

47.8 (38.0, 57.6)f

5 (17)

43.9 (23.4, 64.3)

Itch NRS (≥4 point improvement) d, e

59 (71)

8 (20)

51.1 (35.3, 66.9)f

Not evaluated

---

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

 

Updated on 3 July 2020 PIL

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision
  • Change to information for healthcare professionals

Free text change information supplied by the pharmaceutical company

  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.

 

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:

 

Children’s Body Weight

Recommended Starting Dose (Week 0)

Recommended Dose every 4 weeks (Q4W) Thereafter

Greater than 50 kg

160 mg (2 syringes)

80 mg (1 syringe)

25 to 50 kg

80 mg (1 syringe)

40 mg (dose preparation required)

 

40 mg preparation of ixekizumab in children

Ixekizumab doses of 40 mg must be prepared and administered by a qualified healthcare professional.

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 June 2020.

 

--------------------------------------------------------------------------------------------------------------------------

 

 

The following information is intended for medical or healthcare professionals only:

 

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.

 

 

Updated on 10 June 2020 PIL

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - dose and frequency
  • Change to section 4 - possible side effects
  • Change to section 4 - how to report a side effect
  • Change to section 5 - how to store or dispose
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

  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 spine.psoriatic arthritis.

Psoriatic arthritis

Taltz is used to treat a condition called “psoriatic arthritis” in adults, an inflammatory disease of the joints, …

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 syringes 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 syringeone injection) at Weeks 2, 4, 6, 8, 10, and 12. From Week 12, you will use an 80 mg dose (1 syringeone 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 syringes 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 syringeone injection) at Weeks 2, 4, 6, 8, 10, and 12. From Week 12, you will use an 80 mg dose (1 syringeone injection) every 4 weeks.

For other psoriatic arthritis patients:

  • The first dose is 160 mg (2 syringes 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 syringeone injection) every 4 weeks.

Axial Spondyloarthritis

The recommended dose is 160 mg (2 syringes with 80 mg each) by subcutaneous injection at Week 0, followed by 80 mg (1 syringe) 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.

4.       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

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,

5.       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.

 This leaflet was last revised in January 2018June 2020.

 

Updated on 10 June 2020 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text
  • Improved presentation of SmPC

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Added (underline) deleted (strikethrough)

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

 

 

COAST-V, biologic-naive

COAST-W, TNF-inhibitor experienced

Taltz

80 mg

Q4Wa

(N=81)

 

Placebo (N=87)

 

Difference from placebo g 

Adalimumab

40 mg

Q2W

(N=90)

 

Taltz

80 mg

Q4Wc

(N=114)

 

Placebo (N=104)

 

Difference from placebo g 

ASAS20 responseb, n (%), NRI

52 (64.2%)

35 (40.2%)

24.0 (9.3,  38.6) **

53 (58.9%)

55 (48.2%)

31 (29.8%)

18.4 (5.7, 31.1) **

ASAS40 responseb,c, n (%), NRI

39 (48.1%)

16 (18.4%)

29.8 (16.2, 43.3) ***

32 (35.6%)

29 (25.4%)

13 (12.5%)

12.9 (2.7, 23.2) *

ASDAS

Change from Baseline

Baseline

-1.4
3.7

-0.5
3.9

-1.0 (-1.3, -0.7) ***

-1.3***
3.7

‑1.2
4.2

-0.1
4.1

-1.1 (-1.3, -0.8) ***

BASDAI Score

Change from Baseline
Baseline

-2.9
6.8 i

-1.4
6.8 i

-1.5 (-2.1, -0.9) ***

-2.5***
6.7 i

‑2.2
7.5

-0.9
7.3

-1.2 (-1.8, -0.7) ***

MRI Spine SPARCCd

Change from Baseline
Baseline

‑11.0
14.5

-1.5
15.8

-9.5 (-12.6, -6.4) ***

-11.6***
20.0

‑3.0
8.3

3.3
6.4

-6.3 (-10.0, -2.5) **

BASDAI50e n (%), NRI

34 (42.0%)

15 (17.2%)

24.7 (11.4, 38.1) ***

29 (32.2%)*

25 (21.9%)i

10 (9.6%)i

12.3 (2.8, 21.8)*

ASDAS <2.1, n (%) (Low Disease Activity), NRI

35 (43.2%)h

11 (12.6%)h

30.6 (17.7, 43.4) ***

34 (37.8%)*** h

20 (17.5%)

5 (4.8%)

12.7 ( 4.6, 20.8) **

ASDAS <1.3, n (%) (Inactive Disease), NRI

13 (16.0%)

2 (2.3%)

13.8 (5.2, 22.3) **

14 (15.6%)**

4 (3.5%)i

1 (1.0%)i

2.5 (-1.3, 6.4)

ASAS HI
Change from Baseline
Baseline

 

-2.4
7.5

 

-1.3
8.1

 

-1.1 (-2.0, -0.3) *

 

-2.3*
8.2

 

‑1.9

10.0

 

-0.9
9.0

 

-1.0 (-1.9, -0.1) *

SF-36 PCS

Change from Baseline
Baseline

 

7.7
34.0

 

3.6
32.0

 

4.1 (1.9, 6.2) ***

 

6.9**
33.5

 

6.6
27.5

 

1.4
30.6

 

5.2 (3.0, 7.4) ***

Abbreviations:  N = number of patients in the intent-to-treat population; NRI = Non-responder Imputation; patients with missing data were counted as non-responders.
ASAS HI = Assessment of SpondyloArthritis International Society Health Index; ASDAS = Ankylosing Spondylitis Disease Activity Score; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; CFB = least square mean change from baseline at Week 16; MRI Spine SPARCC = Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Scoring of the Spine (23 discovertebral unit scale)

a             At Week 0, patients received 80 mg or 160 mg of Taltz.

b             An ASAS20 response is defined as a ≥20% improvement and an absolute improvement from baseline of ≥1 unit (range 0 to 10) in ≥3 of 4 domains (Patient Global, Spinal Pain, Function, and Inflammation), and no worsening of ≥20% and ≥1 unit (range 0 to 10) in the remaining domain. An ASAS40 response is defined as a ≥40% improvement and an absolute improvement from baseline of ≥2 units in ≥3 of 4 domains without any worsening in the remaining domain.

c             Primary endpoint.

d             The numbers of ITT patients with MRI data at baseline are as follows: COAST-V: Taltz, n = 81; PBO, n = 82; ADA, n=85. COAST-W: Taltz, n = 58; PBO, n = 51.

e             BASDAI50 response defined as an improvement of ≥50% of the BASDAI score from baseline.

f              ASAS HI: Assessment of SpondyloArthritis International Society Health Index (ASAS HI) across all domains.

g The reported values are difference in %( 95% CI) for categorical variables, and difference in LSM(95% CI)for continuous variables.

h post hoc analysis, not multiplicity corrected.

i prespecified, but not multiplicity gated.

* p<0.05; ** p<0.01; *** p<0.001 compared with placebo.

There were improvements in the main components of the ASAS40 response criteria (spinal pain, BASFI, patient global assessment, stiffness) and other measures of disease activity, including CRP, at Week 16.

The percent of patients achieving an ASAS40 response by visit in COAST-V and COAST-W is shown in Figure 4.

 Figure 4.             ASAS40 Responses in COAST-V and COAST-W through Week 16, NRIa

a    Patients with missing data were counted as non-responders.

* p<0.05; ** p<0.01; *** p<0.001 compared with placebo.

Similar response in ASAS40 was seen in patients regardless of baseline CRP levels, baseline ASDAS scores and MRI spine SPARCC scores. The ASAS40 response was demonstrated regardless of age, gender, race, disease duration, baseline body weight, baseline BASDAI score and prior biologic treatment.

In COAST-V and COAST-W efficacy was maintained up to Week 52 as assessed by the endpoints presented in Table 10, including ASAS20, ASAS40, ASDAS, BASDAI, and ASAS HI response rates.

Health-Related Outcomes

Spinal pain showed improvements versus placebo as early as Week 1, maintained through Week 16 [Taltz vs placebo: COAST-V -3.2 vs -1.7; COAST-W -2.4 vs -1.0]; fatigue and spinal mobility showed improvements versus placebo at Week 16. Improvements in spinal pain, fatigue and spinal mobility were maintained through Week 52.

Non-radiographic Axial Spondyloarthritis

The efficacy and safety of Taltz were assessed in a randomised, double-blind, study with a 52‑week placebo-controlled period (COAST-X) in 303 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 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 16.

At baseline, patients had symptoms of non-radiographic axSpA for an average of 11 years. Approximately 39% of the patients were on a concomitant cDMARD.

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

 Clinical Response

Higher proportions of patients treated with Taltz 80 mg Q4W achieved ASAS40 response compared to placebo at Week 16 (Table 11). Responses were similar regardless of concomitant therapies.

Table 11.             Efficacy results at Week 16 in COAST-X, NRI a,b

 

 

Taltz 80 mg Q4Wc

(N=96)

 

Placebo

(N=105)

 

Difference from placebo h 

ASAS20 responsed, n (%), NRI

52 (54.2%)

41 (39.0%)

15.1 (1.5, 28.8)*

ASAS40 responsed,e, n (%),  NRI

34 (35.4%)

20 (19.0%)

16.4 (4.2, 28.5)**

ASDAS

Change from Baseline
Baseline

-1.1
3.8

-0.6
3.8

-0.5 (-0.8, -0.3) ***

BASDAI Score

Change from Baseline
Baseline

-2.2
7.0

-1.5
7.2

-0.7 (-1.3, -0.1) *

MRI SIJ SPARCCf

Change from Baseline
Baseline

-3.4
5.1

-0.3
6.3

-3.1 (-4.6, -1.6) ***

ASDAS <2.1, n (%)
(Low Disease Activity), NRIg

26 (27.7%)

13 (12.4%)

15.3 (4.3, 26.3) **

SF-36 PCS

Change from Baseline
Baseline

8.1
33.5

5.2
32.6

2.9 (0.6, 5.1) *

a Abbreviations: N = number of patients in the intent-to-treat population; NRI = Non-responder Imputation. ASDAS = Ankylosing Spondylitis Disease Activity Score; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; Change from Baseline = least square mean change from baseline at Week 16; MRI SIJ SPARCC = Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Scoring of the sacroiliac joint.

b Patients with missing data were counted as non-responders.

c  At Week 0, patients received 80 mg or 160 mg of Taltz.

d An ASAS20 response is defined as a ≥20% improvement and an absolute improvement from baseline of ≥1 units (range 0 to 10) in ≥3 of 4 domains (Patient Global, Spinal Pain, Function, and Inflammation), and no worsening of ≥20% and ≥1 unit (range 0 to 10) in the remaining domain. An ASAS40 response is defined as a ≥40% improvement and an absolute improvement from baseline of ≥2 units in ≥3 of 4 domains without any worsening in the remaining domain.

e  Primary endpoint at Week 16.

f  The numbers of ITT patients with MRI data at baseline and Week 16 are as follows: Taltz, n = 85; PBO, n = 90.

g Patients with missing data were counted as non-responders. Percentages are based on the number of patients in the ITT population with baseline ASDAS ≥2.1.

h The reported values are difference in %( 95% CI) for categorical variables, and difference in LSM(95% CI) for continuous variables.

* p<0.05; ** p<0.01; *** p<0.001 compared with placebo.

The improvement in the main components of the ASAS40 response criteria (spinal pain, BASFI, patient global assessment, stiffness) and other measures of disease activity demonstrated significant clinical improvement at Week 16.

The percent of patients achieving ASAS40 response by visit is shown in Figure 5.

Figure 5.              ASAS40 Response through Week 16 in COAST-X, NRIa

 

a    Patients with missing data were counted as non-responders.

** p<0.01 compared with placebo.

In COAST-X efficacy was maintained up to Week 52 as assessed by the endpoints presented in Table 11.

Health-Related Outcomes

Spinal pain showed improvements versus placebo as early as Week 1 and was maintained through Week 16 [Taltz vs placebo: COAST-X: -2.4 vs -1.5]. In addition, more patients on Taltz compared with placebo achieved good health status (ASAS HI ≤5) at Week 16 and Week 52.

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with Taltz in one or more subsets of the paediatric population in the treatment of plaque psoriasis and psoriatic arthritis/axial spondyloarthritis (see section 4.2 for information on paediatric use).

5.2         Pharmacokinetic properties

Psoriatic arthritis Pharmacokinetic Properties Across Indications

The pharmacokinetic properties of Taltz were similar across the plaque psoriasis, psoriatic arthritis, radiographic axial spondyloarthritis and non-radiographic axial spondyloarthritis indications. observed in psoriatic arthritis patients were similar to those displayed in plaque psoriasis patients. The bioavailability of Taltz in psoriatic arthritis patients was in the range of 61-84% on the basis of the population pharmacokinetic model

6.4         Special precautions for storage

Store in a refrigerator (2 ºC -to 8 ºC).

6.6         Special precautions for disposal and other handling

 Instructions for use

The instructions for using the pen, included with the package leaflet, must be followed carefully.

 10.         DATE OF REVISION OF THE TEXT

 18 July 2019 02 June 2020

TA7MTA8M

Updated on 20 August 2019 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 

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.

 

Cytochrome P450 Substrates

 

Results from a drug-drug interaction study in patients with moderate-to-severe psoriasis determined that 12 weeks of administration of ixekizumab with drugs metabolized 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 drugs.

No formal in vivo drug-drug interaction studies have been conducted. A role for IL‑17 in the regulation of CYP450 enzymes has not been reported. The formation of some CYP450 enzymes is, however, suppressed by increased levels of cytokines during chronic inflammation. Thus, anti‑inflammatory treatments, such as with the IL-17A inhibitor ixekizumab, may result in normalisation of CYP450 levels with accompanying lower exposure of CYP450-metabolised co-medications. Therefore, a clinically relevant effect on CYP450 substrates with a narrow therapeutic index, where the dose is individually adjusted (e.g. warfarin), cannot be excluded. On initiation of ixekizumab therapy in patients being treated with these types of medicinal products, therapeutic monitoring should be considered.

 

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, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517; Website: www.hpra.ie; e-mail: medsafety@hpra.ie, or United Kingdom: 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

 

….

 

Postmarketing Phase 4, direct comparative study

Efficacy and safety of Taltz was investigated in a multicenter, randomized, open-label, rater-blinded, parallel-group study (SPIRIT-H2H) compared to adalimumab (ADA) in 566 patients with PsA who were naïve to biologic disease-modifying anti-rheumatic drugs (bDMARD). Patients were stratified at baseline based on concomitant cDMARD use and presence of moderate-to-severe psoriasis (PASI≥12, BSA≥10 and sPGA≥3).

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.

 

Figure 3: Primary Endpoint (Simultaneous ACR 50 & PASI 100) and Major Secondary Endpoints (ACR 50; PASI 100) Response Rates Week 0 – 24 [ITT population, NRI]**

*GRAPH*

 

** Taltz 160 mg Week 0, then 80 mg every 2 weeks to Week 12 and every 4 weeks thereafter for patients with moderate to severe plaque psoriasis or 160 mg Week 0, then 80 mg every 4 week for other patients, ADA 80 mg Week 0, then 40 mg every 2 weeks from Week 1 for patients with moderate to severe plaque psoriasis or 40 mg Week 0, then 40 mg every 2 weeks for other patients.

Significance level only provided for endpoint that was pre-defined and multiplicity tested.

 

10.          DATE OF REVISION OF THE TEXT

 

24 May 201818 July 2019

 

 

TA6MTA7M

Updated on 29 August 2018 Ed-Ptnt

Reasons for updating

  • Add New Doc

Updated on 24 August 2018 SmPC

Reasons for updating

  • File format updated to PDF

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 28 June 2018 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 27 June 2018 SmPC

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  • Change to section 5.1 - Pharmacodynamic properties
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Free text change information supplied by the pharmaceutical company

5.1          Pharmacodynamic properties

 […]

Efficacy in Genital Psoriasis

[…]

            Table 7     Efficacy Results at Week 12 in Adults with Genital Psoriasis in Trial IXORA-Q; NRI a

            […]

 […]

 Also changes to table references in text where applicable.

 10.     DATE OF REVISION OF THE TEXT

           19 April 2018 24 May 2018

 

                                                                                                                                              TA5MTA6M

Updated on 29 May 2018 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

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Added, deleted, summary of changes or formatting

 

4.2          Posology and method of administration

The solution/the syringe/pen must not be shaken.

 

5.1          Pharmacodynamic properties

Patients randomised to Taltz who were sPGA (0,1) responders (static Physicians Global Assessment) at […].

In all three studies, […] PASI 75 response (Psoriasis Area and Severity Index) and […]

 

Postmarketing Phase 3b, direct comparative study
Efficacy and safety of ixekizumab was also investigated in a double-blind study compared to ustekinumab with ixekizumab being superior 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.

 

Table 6.           PASI-Response Rates from comparative study ixekizumab versus ustekinumab

 

[Addition of Table]

 

                        Table 76

 

                                                Minimal Disease Activity (MDA) n (%)

 

Table 87

 

SD = standard deviation.

 

Changes to table references in text where applicable.

 

10.     DATE OF REVISION OF THE TEXT

18 January 2018 19 April 2018

TA45M

Updated on 25 January 2018 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 25 January 2018 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
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4.       CLINICAL PARTICULARS

 

4.1          Therapeutic indications   

 

Plaque psoriasis

 

Taltz is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.

 

Psoriatic arthritis

 

Taltz, alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drug (DMARD) therapies (see section 5.1).

 

4.2          Posology and method of administration

 

Taltz is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which Taltz is indicatedpsoriasis.

 

Posology

Plaque psoriasis

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.

 

Psoriatic arthritis

The recommended dose is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg (one injection) every 4 weeks thereafter. For psoriatic arthritis patients with concomitant moderate to severe plaque psoriasis, the recommended dosing regimen is the same as for plaque psoriasis.

 

Consideration should be given to discontinuing treatment in patients who have shown no response after 16 to 20 weeks of treatment. Some patients with initially partial response may subsequently improve with continued treatment beyond 20 weeks.

 

Paediatric population

The safety and efficacy of Taltz in children 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.

 

4.5          Interaction with other medicinal products and other forms of interaction

 

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

 

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

 

4.8          Undesirable effects

 

Updated throughout including re-formatted table to include PsA and additional data including addition of Herpes simplex (mucocutaneous), rash and eczema.

 

5.       PHARMACOLOGICAL PROPERTIES

 

5.1          Pharmacodynamic properties

 

                        Updated throughout to include PsA data.

 

5.2          Pharmacokinetic properties

 

                        Updated throughout to include PsA data.

 

6.       PHARMACEUTICAL PARTICULARS

 

6.6          Special precautions for disposal and other handling

 

Instructions for use

 

Pre-filled syringe

The instructions for using the syringe, included with the package leaflet, must be followed carefully.

The pre-filled syringe is for single use only.

Taltz should not be used if particles appear or if the solution is cloudy and/or distinctly brown.

Taltz that has been frozen must not be used.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

 

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

          Date of first authorisation: 25 April 2016

 

 

10.     DATE OF REVISION OF THE TEXT

 

          18 January 2018

 

 

 

                                                                                                                                                        TA4M

Updated on 24 January 2018 PIL

Reasons for updating

  • New PIL for new product

Updated on 24 January 2018 PIL

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 11 January 2018 PIL

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 4 - how to report a side effect
  • Change to section 6 - date of revision

Updated on 11 January 2018 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes

 

Added (underline) deleted (strikethrough)

 

 

TALTZ® (ixekizumab)

 

1.         NAME OF THE MEDICINAL PRODUCT

 

Taltz]80 mg solution for injection in pre-filled syringe.

Taltz 80 mg solution for injection in pre-filled pen.

 

4.4          Special warnings and precautions for use

Hypersensitivity

Serious hypersensitivity reactions, including some cases of anaphylaxis, angioedema, urticaria and, rarely, late (10-14 days following injection) serious hypersensitivity reactions including widespread urticaria, dyspnea and high antibody titres have been reported. If a serious hypersensitivity reaction occurs, administration of Taltz should be discontinued immediately and appropriate therapy initiated.

 

Tabulated list of adverse reactions

ADRs from clinical studies and postmarketing reports (Table 1) are listed by MedDRA system organ class.

 

 

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

 

System Organ Class

Taltz

Placebo

Q4W

(N = 1161)

n (%)

Q2W

(N = 1167)

n (%)

 

(N = 791)

n (%)

Infections and infestations

Very Common

Upper respiratory tract infectionb

155 (13.4)

163 (14.0)

101 (12.8)

Common

Tinea infection

10 (0.9)

17 (1.5)

1 (0.1)

Uncommon

 

Influenza

10 (0.9)

8 (0.7)

0

Rhinitis

10 (0.9)

9 (0.8)

0

Oral candidiasisc

2 (0.2)

9 (0.8)

0

Conjunctivitis

1 (0.1)

8 (0.7)

3 (0.4)

Cellulitisd

10 (0.9)

9 (0.8)

2 (0.3)

Blood and lymphatic system disorders

Uncommon

Neutropeniaf

3 (0.3)

6 (0.5)

1 (0.1)

Thrombocytopeniaf

2 (0.2)

2 (0.2)

0

Immune system disordersg

Rare

Anaphylaxisg

N/A

N/A

N/A

Respiratory, thoracic, and mediastinal disorders

Common

Oropharyngeal pain

20 (1.7)

16 (1.4)

4 (0.5)

Gastrointestinal disorders

Common

Nausea

15 (1.3)

23 (2.0)

5 (0.6)

Skin and subcutaneous tissue disorders

Uncommon

Urticaria

6 (0.5)

10 (0.9)

0

General disorders and administration site conditions

Very Common

Injection site reactions e

150 (12.9)

196 (16.8)

26 (3.3)

a Placebo-controlled clinical studies (phase III) in moderate to severe plaque psoriasis patients exposed to ixekizumab 80 mg Q2W, ixekizumab 80 mg Q4W or placebo for up to 12 weeks of treatment duration

b Upper respiratory tract infection includes nasopharyngitis and upper respiratory tract infection

c Oral candidiasis defined as events with the preferred terms oral candidiasis and oral fungal infection

d Cellulitis includes staphylococcal and external ear cellulitis, and erysipelas

e 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)

f Based on reported adverse events

g Based on postmarketing reports

 

 

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, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517; Website: www.hpra.ie; e-mail: medsafety@hpra.ie, or United Kingdom: Yellow Card Scheme; Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

 

 

10.       DATE OF REVISION OF THE TEXT

 

                08th December 2017 12 October 2017

TALTZ] (Ixekizumab) is a trademark of Eli Lilly and Company TA2MTA3M

Updated on 19 October 2016 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Added (bold) deleted (strikethrough)

 

5.1          Pharmacodynamic properties

 

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

 

Endpoints

Number of patients (%)

Difference from Placebo in Response Rate (95% CI)

Placebo
(N = 168)

Taltz

80 mg Q4W

(N = 347)

Taltz
80 mg Q2W
(N = 351)

Etanercept
50 mg twice weekly
(N = 358)

Taltz

80 mg Q4W

 

Taltz
80 mg Q2W

sPGA of “0” (clear) or “1” (minimal)

4 (2.4)

253 (72.9)a

292 (83.2)a

129 (36.0)

70.5 (65.3, 75.7)

80.8 (76.3, 85.4)

sPGA of “0” (clear)

1 (0.6)

112 (32.3)a,b

147 (41.9)a,b

21 (5.9)c

31.7 (26.6, 36.7)

41.3 (36.0, 46.6)

PASI 75

4 (2.4)

269 (77.5)a,b

315 (89.7)a,b

149 (41.6)a

75.1 (70.2, 80.1)

87.4 (83.4, 91.3)

PASI 90

1 (0.6)

207 (59.7)a,b

248 (70.7)a,b

67 (18.7)a

59.1 (53.8, 64.4)

70.1 (65.2, 75.0)

PASI 100

1 (0.6)

107 (30.8)a,b

142 (40.5)a,b

19 (5.3)c

30.2 (25.2, 35.2)

39.9 (34.6, 45.1)

Itch NRS reduction ≥ 4d

19 (14.1)

225 (76.8)a,b

258 (85.1)a,b

177 (57.8)a

62.7 (55.1, 70.3)

71.1 (64.0, 78.2)

Abbreviations: N = number of patients in the intent-to-treat population

Note: patients with missing data were counted as non-responders.

a p < 0.001 compared with placebo

b p < 0.001 compared with etanercept

c p < 0.01 compared with placebo

d Patients with Itch NRS > = 4 at baseline: placebo N = 135, Taltz 80 mg Q4W N = 293, Taltz 80 mg Q2W N = 303, Etanercept N = 306

 

 

6.4          Special precautions for storage

 

Store in a refrigerator (2 ºC – 8 ºC).

Do not freeze.

Store in the original package in order to protect from light.

 

Taltz may be stored unrefrigerated for up to 5 days at a temperature not above 30 °C.

 

 

10.       DATE OF REVISION OF THE TEXT

 

                25 April 201612 October 2016

 

 

]TALTZ (Ixekizumab) is a trademark of Eli Lilly and Company.                                                           TA12M

Updated on 19 October 2016 PIL

Reasons for updating

  • Change to section 5 - how to store or dispose
  • Change to section 6 - date of revision

Updated on 6 June 2016 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

None provided

Updated on 3 June 2016 PIL

Reasons for updating

  • New PIL for new product