Imraldi 40mg solution for injection in pre-filled pen

Product Information *

  • Company:

    Biogen Biosimilar
  • Status:

    Updated
  • Active Ingredients :

    This medicinal product is subject to additional monitoring.

    *Additional information is available upon request

  • Legal Category:

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

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 23 July 2021

File name

Imraldi IE MT NIR 40mg PFP PL July 21_1627029380.pdf

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 3 - dose and frequency
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

1.       What Imraldi is and what it is used for

Ulcerative colitis in adults and children

Ulcerative colitis is an inflammatory disease of the bowel large intestine.

Imraldi is used to treat moderate to severe ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis you will may first be given other medicines. If these medicines do not work well enough, you will be given Imraldi to reduce the signs and symptoms of your disease.

 

3.       How to use Imraldi

Adults with ulcerative colitis

The usual Imraldi dose for adults with ulcerative colitis is 160 mg initially (as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days) followed by 80 mg (as two 40 mg injections in one day) two weeks later and thereafter 40 mg every other week. If this dose does not work well enough, your

doctor may increase the dose to 40 mg every week or 80 mg every other week.

Children and adolescents with ulcerative colitis

Children and adolescents from 6 years of age weighing less than 40 kg

The usual Imraldi dose is 80 mg (as two 40 mg injections in one day) initially

followed by 40 mg (as one 40 mg injection) two weeks later. Thereafter, the usual dose is 40 mg every other week.

Patients who turn 18 years of age while on 40 mg every other week, should continue their prescribed dose.

Children and adolescents from 6 years of age weighing 40 kg or more

The usual Imraldi dose is 160 mg (as four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) initially, followed by 80 mg (as two

40 mg injections in one day) two weeks later. Thereafter the usual dose is 80 mg every other week.

Patients who turn 18 years of age while on 80 mg every other week, should continue their prescribed dose.

 

Updated on 23 July 2021

File name

Imraldi IE MT NIR SPC July 21_1627025476.pdf

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 5.2 - Pharmacokinetic properties
  • Change to section 6.5 - Nature and contents of container
  • 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

  

Section 4.1

Paediatric ulcerative colitis

Imraldi is indicated for the treatment of moderately to severely active ulcerative colitis in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.

Section 4.2  

The safety and efficacy of adalimumab in children aged 4-17 years have not yet been established. No data are available. There is no relevant use of Imraldi in children aged less than 4 years for this indication.

The recommended dose of Imraldi for patients from 6 to 17 years of age with ulcerative colitis is based on body weight (Table 5). Imraldi is administered via subcutaneous injection.

Table 5 Imraldi Dose for Paediatric Patients with Ulcerative Colitis

Patient Weight

Induction Dose

Maintenance Dose

Starting at Week 4*

< 40 kg

  • 80 mg at week 0 (given as two 40 mg injections in one day) and
  • 40 mg at week 2 (given as one 40 mg injection)
  • 40 mg every other week

≥ 40 kg

  • 160 mg at week 0 (given as four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) and
  • 80 mg at week 2 (given as two 40 mg injections in one day)
  • 80 mg every other week

* Paediatric patients who turn 18 years of age while on Imraldi should continue their prescribed maintenance dose.

Continued therapy beyond 8 weeks should be carefully considered in patients not showing signs of response within this time period.

There is no relevant use of Imraldi in children aged less than 6 years in this indication.

Imraldi may be available in different strengths and/or presentations depending on the individual treatment needs.

Section 4.8:

Malignancies and lymphoproliferative disorders

No malignancies were observed in 249 paediatric patients with an exposure of 655.6 patient years during adalimumab trials in patients with juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis). In addition, no malignancies were observed in 192 paediatric patients with an exposure of 498.1 patient years during adalimumab trials in paediatric patients with Crohn’s disease. No malignancies were observed in 77 paediatric patients with an exposure of 80.0 patient years during an adalimumab trial in paediatric patients with chronic plaque psoriasis. No malignancies were observed in 93 paediatric patients with an exposure of 65.3 patient years during an adalimumab trial in paediatric patients with ulcerative colitis. No malignancies were observed in 60 paediatric patients with an exposure of 58.4 patient years during an adalimumab trial in paediatric patients with uveitis.

.......

In the controlled Phase 3 trial of adalimumab in patients with paediatric ulcerative colitis (N=93) which evaluated efficacy and safety of a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week (N=31) and a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every Week (N=32), following body weight adjusted induction dosing of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 (N=63), or an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2 (N=30), ALT elevations ≥ 3 X ULN occurred in 1.1% (1/93) of patients.

Section 5.1:

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of the studies with the reference medicinal product containing adalimumab in one or more subsets of the paediatric population in ulcerative colitis, see section 4.2 for information on paediatric use.

Sections on Juvenile idiopathic arthritis (JIA), Enthesitis-related arthritis, Paediatric plaque psoriasis, Adolescent hidradenitis suppurativa, Paediatric Crohn’s disease and Paediatric Uveitis have been deleted and the following text has been added:

Juvenile idiopathic arthritis (JIA)

Polyarticular juvenile idiopathic arthritis (pJIA)

The safety and efficacy of adalimumab was assessed in two studies (pJIA I and II) in children with active polyarticular or polyarticular course juvenile idiopathic arthritis, who had a variety of JIA onset types (most frequently rheumatoid-factor negative or positive polyarthritis and extended oligoarthritis).

pJIA I

The safety and efficacy of adalimumab were assessed in a multicentre, randomised, double-blind, parallel-group study in 171 children (4-17 years old) with polyarticular JIA. In the open-label lead in phase (OL LI) patients were stratified into two groups, MTX (methotrexate)-treated or non-MTX- treated. Patients who were in the non-MTX stratum were either naïve to or had been withdrawn from MTX at least two weeks prior to study drug administration. Patients remained on stable doses of non-steroidal anti-inflammatory drugs (NSAIDs) and or prednisone (≤ 0.2 mg /kg/day or 10 mg/day maximum). In the OL LI phase all patients received 24 mg/m2 up to a maximum of 40 mg adalimumab every other week for 16 weeks. The distribution of patients by age and minimum, median and maximum dose received during the OL LI phase is presented in Table 25.

Table 25

Distribution of patients by age and adalimumab dose received during the OL LI phase

Age Group

Number of patients at Baseline N (%)

Minimum, median and maximum dose

4 to 7 years

31 (18.1)

10, 20 and 25 mg

8 to 12 years

71 (41.5)

20, 25 and 40 mg

13 to 17 years

69 (40.4)

25, 40 and 40 mg

Patients demonstrating a Paediatric ACR 30 response at week 16 were eligible to be randomised into the double blind (DB) phase and received either adalimumab 24 mg/m2 up to a maximum of 40 mg, or placebo every other week for an additional 32 weeks or until disease flare. Disease flare criteria were defined as a worsening of ≥30% from baseline in ≥3 of 6 Paediatric ACR core criteria, ≥2 active joints, and improvement of >30% in no more than 1 of the 6 criteria. After 32 weeks or at disease flare, patients were eligible to enrol into the open label extension phase.

Table 26

Paed ACR 30 Responses in the JIA study

Stratum

MTX

Without MTX

Phase

OL-LI 16 weeks

Ped ACR 30 response (n/N)

94.1 % (80/85)

74.4 % (64/86)

Efficacy Outcomes

Double Blind 32 weeks

Adalimumab /MTX

(N=38)

Placebo / MTX (N=37)

Adalimumab

(N=30)

Placebo

(N=28)

Disease flares at the end of 32 weeksa (n/N)

36.8 % (14/38)

64.9 % (24/37)b

43.3 % (13/30)

71.4 % (20/28)c

Median time to disease flare

>32 weeks

20 weeks

>32 weeks

14 weeks

a Ped ACR 30/50/70 responses week 48 significantly greater than those of placebo treated patients

b p = 0.015

c p = 0.031

Amongst those who responded at week 16 (n=144), the Paediatric ACR 30/50/70/90 responses were maintained for up to six years in the OLE phase in patients who received adalimumab throughout  the study. Over all 19 subjects, of which 11 of the baseline age group 4 to 12 and 8 of the baseline age group 13 to 17 years were treated 6 years or longer.

Overall responses were generally better and, fewer patients developed antibodies when treated with the combination of adalimumab and MTX compared to adalimumab alone. Taking these results into consideration, adalimumab is recommended for use in combination with MTX and for use as monotherapy in patients for whom MTX use is not appropriate (see section 4.2).

pJIA II

The safety and efficacy of adalimumab was assessed in an open-label, multicentre study in 32 children (2 - <4 years old or aged 4 and above weighing <15 kg) with moderately to severely active polyarticular JIA. The patients received 24 mg/m2 body surface area (BSA) of adalimumab up to a maximum of 20 mg every other week as a single dose via SC injection for at least 24 weeks. During the study, most subjects used concomitant MTX, with fewer reporting use of corticosteroids or NSAIDs.

At week 12 and week 24, PaedACR30 response was 93.5% and 90.0%, respectively, using the observed data approach. The proportions of subjects with PaedACR50/70/90 at week 12 and week 24 were 90.3%/61.3%/38.7% and 83.3%/73.3%/36.7%, respectively. Amongst those who responded (Paediatric ACR 30) at week 24 (n=27 out of 30 patients), the Paediatric ACR 30 responses were maintained for up to 60 weeks in the OLE phase in patients who received adalimumab throughout this time period. Overall, 20 subjects were treated for 60 weeks or longer.

Enthesitis-related arthritis

The safety and efficacy of adalimumab were assessed in a multicentre, randomised, double-blind study in 46 paediatric patients (6 to 17 years old) with moderate enthesitis-related arthritis. Patients were randomised to receive either 24 mg/m2 body surface area (BSA) of adalimumab up to a maximum of 40 mg, or placebo every other week for 12 weeks. The double-blind period is followed by an open-label (OL) period during which patients received 24 mg/m2 BSA of adalimumab up to a maximum of 40 mg every other week subcutaneously for up to an additional 192 weeks. The primary endpoint was the percent change from Baseline to week 12 in the number of active joints with arthritis (swelling not due to deformity or joints with loss of motion plus pain and/or tenderness), which was achieved with mean percent decrease of -62.6% (median percent change -88.9 %) in patients in the adalimumab group compared to -11.6% (median percent change -50.0 %) in patients in the placebo group. Improvement in number of active joints with arthritis was maintained during the OL period through week 156 for the 26 of 31 (84 %) patients in the adalimumab group who remained in the study. Although not statistically significant, the majority of patients demonstrated clinical improvement in secondary endpoints such as number of sites of enthesitis, tender joint count (TJC), swollen joint count (SJC), Paediatric ACR 50 response, and Paediatric ACR 70 response.

Paediatric plaque psoriasis

The efficacy of adalimumab was assessed in a randomised, double-blind, controlled study of 114 paediatric patients from 4 years of age with severe chronic plaque psoriasis (as defined by a PGA ≥4 or >20% BSA involvement or >10 % BSA involvement with very thick lesions or PASI ≥20 or ≥10 with clinically relevant facial, genital, or hand/ foot involvement) who were inadequately controlled with topical therapy and heliotherapy or phototherapy.

Patients received adalimumab 0.8 mg/kg eow (up to 40 mg), 0.4 mg/kg eow (up to 20 mg), or methotrexate 0.1 – 0.4 mg/kg weekly (up to 25 mg). At Week 16, more patients randomised to adalimumab 0.8 mg/kg had positive efficacy responses (e.g., PASI 75) than those randomised to 0.4 mg/kg eow or MTX.

Table 27

Paediatric Plaque Psoriasis Efficacy Results at 16 Weeks

 

MTXa

N=37

Adalimumab 0.8 mg/kg eow

N=38

PASI 75b

12 (32.4%)

22 (57.9%)

PGA: Clear/minimalc

15 (40.5%)

23 (60.5%)

a MTX = methotrexate

b P=0.027, adalimumab 0.8 mg/kg versus MTX

c P=0.083, adalimumab 0.8 mg/kg versus MTX

Patients who achieved PASI 75 and PGA clear or minimal were withdrawn from treatment for up to 36 weeks and monitored for loss of disease control (i.e. a worsening of PGA by at least 2 grades). Patients were then re-treated with adalimumab 0.8 mg/kg eow for an additional 16 weeks and response rates observed during retreatment were similar to the previous double-blind period: PASI 75 response of 78.9 % (15 of 19 subjects) and PGA clear or minimal of 52.6 % (10 of 19 subjects).

In the open label period of the study, PASI 75 and PGA clear or minimal responses were maintained for up to an additional 52 weeks with no new safety findings.

Adolescent hidradenitis suppurativa

There are no clinical trials with adalimumab in adolescent patients with HS. Efficacy of adalimumab for the treatment of adolescent patients with HS is predicted based on the demonstrated efficacy and exposure-response relationship in adult HS patients and the likelihood that the disease course, pathophysiology, and drug effects are substantially similar to that of adults at the same exposure levels. Safety of the recommended adalimumab dose in the adolescent HS population is based on cross-indication safety profile of adalimumab in both adults and paediatric patients at similar or more frequent doses (see section 5.2).

Paediatric Crohn’s disease

Adalimumab was assessed in a multicentre, randomised, double-blind clinical trial designed to evaluate the efficacy and safety of induction and maintenance treatment with doses dependent on body weight (<40 kg or ≥40 kg) in 192 paediatric subjects between the ages of 6 and 17 (inclusive) years, with moderate to severe Crohn´s disease (CD) defined as Paediatric Crohn's Disease Activity Index (PCDAI) score >30. Subjects had to have failed conventional therapy (including a corticosteroid and/or an immunomodulator) for CD. Subjects may also have previously lost response or been intolerant to infliximab.

All subjects received open-label induction therapy at a dose based on their Baseline body weight: 160 mg at week 0 and 80 mg at week 2 for subjects ≥40 kg, and 80 mg and 40 mg, respectively, for subjects <40 kg.

At week 4, subjects were randomised 1:1 based on their body weight at the time to either the Low Dose or Standard Dose maintenance regimens as shown in Table 28.

Table 28

Maintenance regimen 

Patient Weight

Low dose

Standard dose

<40 kg

10 mg eow

20 mg eow

≥40 kg

20 mg eow

40 mg eow

Efficacy results

The primary endpoint of the study was clinical remission at week 26, defined as PCDAI score ≤10.

Clinical remission and clinical response (defined as reduction in PCDAI score of at least 15 points from Baseline) rates are presented in Table 29. Rates of discontinuation of corticosteroids or immunomodulators are presented in Table 30.

Table 29

Paediatric CD Study

PCDAI Clinical Remission and Response 

 

Standard Dose

40/20 mg eow

N=93

Low Dose

20/10 mg eow

N=95

P value*

Week 26

Clinical remission

38.7 %

28.4 %

0.075

Clinical response

59.1 %

48.4 %

0.073

Week 52

Clinical remission

33.3 %

23.2 %

0.100

Clinical response

41.9 %

28.4 %

0.038

* p value for Standard Dose versus Low Dose comparison 

Table 30

Paediatric CD Study

Discontinuation of Corticosteroids or Immunomodulators and Fistula Remission 

 

Standard Dose

40/20 mg eow

Low Dose

20/10 mg eow

P value1

Discontinued corticosteroids

N=33

N=38

 

Week 26

84.8 %

65.8 %

0.066

Week 52

69.7 %

60.5 %

0.420

Discontinuation of Immunomodulators2

N=60

N=57

 

Week 52

30.0 %

29.8 %

0.983

Fistula remission3

N=15

N=21

 

Week 26

46.7 %

38.1 %

0.608

Week 52

40.0 %

23.8 %

0.303

1 p value for Standard Dose versus Low Dose comparison

2 Immunosuppressant therapy could only be discontinued at or after week 26 at the investigator's discretion if the subject met the clinical response criterion

3 Defined as a closure of all fistulas that were draining at Baseline for at least 2 consecutive post-Baseline visits

Statistically significant increases (improvement) from Baseline to week 26 and 52 in Body Mass Index and height velocity were observed for both treatment groups.

Statistically and clinically significant improvements from Baseline were also observed in both treatment groups for quality of life parameters (including IMPACT III).

One hundred patients (n=100) from the Paediatric CD study continued in an open-label long-term extension study. After 5 years of adalimumab therapy, 74.0 % (37/50) of the 50 patients remaining in the study continued to be in clinical remission, and 92.0 % (46/50) of patients continued to be in clinical response per PCDAI.

Paediatric ulcerative colitis

The safety and efficacy of adalimumab was assessed in a multicenter, randomized, double-blind, trial in 93 paediatric patients from 5 to 17 years of age with moderate to severe ulcerative colitis (Mayo score 6 to 12 with endoscopy subscore of 2 to 3 points, confirmed by centrally read endoscopy) who had an inadequate response or intolerance to conventional therapy. Approximately 16% of patients in the study had failed prior anti-TNF treatment. Patients who received corticosteroids at enrollment were allowed to taper their corticosteroid therapy after Week 4.

In the induction period of the study, 77 patients were randomized 3:2 to receive double-blind treatment with adalimumab at an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2; or an induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2. Both groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and Week 6. Following an amendment to the study design, the remaining 16 patients who enrolled in the induction period received open-label treatment with adalimumab at the induction dose of 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2.

At Week 8, 62 patients who demonstrated clinical response per Partial Mayo Score (PMS; defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized equally to receive double-blind maintenance treatment with adalimumab at a dose of 0.6 mg/kg (maximum of 40 mg) every week (ew), or a maintenance dose of 0.6 mg/kg (maximum of 40 mg) every other week (eow). Prior to an amendment to the study design, 12 additional patients who demonstrated clinical response per PMS were randomized to receive placebo but were not included in the confirmatory analysis of efficacy.

Disease flare was defined as an increase in PMS of at least 3 points (for patients with PMS of 0 to 2 at Week 8), at least 2 points (for patients with PMS of 3 to 4 at Week 8), or at least 1 point (for patients with PMS of 5 to 6 at Week 8).

Patients who met criteria for disease flare at or after Week 12 were randomized to receive a re-induction dose of 2.4 mg/kg (maximum of 160 mg) or a dose of 0.6 mg/kg (maximum of 40 mg) and continued to receive their respective maintenance dose regimen afterwards.

Efficacy Results

The co-primary endpoints of the study were clinical remission per PMS (defined as PMS ≤ 2 and no individual subscore > 1) at Week 8, and clinical remission per FMS (Full Mayo Score) (defined as a Mayo Score ≤ 2 and no individual subscore > 1) at Week 52 in patients who achieved clinical response per PMS at Week 8. Clinical remission rates per PMS at Week 8 for patients in each of the adalimumab doubleblind induction groups are presented in Table 31.

Table 31

Clinical Remission per PMS at 8 Weeks 

 

Adalimumaba

Maximum of 160 mg at Week 0/ Placebo at Week 1

N=30

Adalimumabb, c

Maximum of 160 mg at Week 0 and Week 1

N=47

Clinical remission

13/30 (43.3%)

28/47 (59.6%)

a Adalimumab 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2

b Adalimumab 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2

c Not including open-label Induction dose of adalimumab 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2

Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and Week 6

Note 2: Patients with missing values at Week 8 were considered as not having met the endpoint

At Week 52, clinical remission per FMS in Week 8 responders, clinical response per FMS (defined as a decrease in Mayo Score ≥ 3 points and ≥ 30% from Baseline) in Week 8 responders, mucosal healing (defined as Mayo endoscopy subscore ≤ 1) in Week 8 responders, clinical remission per FMS in Week 8 remitters, and the proportion of subjects in corticosteroid-free remission per FMS in Week 8 responders were assessed in patients who received adalimumab at the double-blind maximum 40 mg eow (0.6 mg/kg) and maximum 40 mg ew (0.6 mg/kg) maintenance doses (Table 32). 

Table 32

Efficacy Results at 52 Weeks

 

Adalimumaba

Maximum of 40 mg eow

N=31

Adalimumabb

Maximum of 40 mg ew

N=31

Clinical remission in Week 8 PMS responders

9/31 (29.0%)

14/31 (45.2%)

Clinical response in Week 8 PMS responders

19/31 (61.3%)

21/31 (67.7%)

Mucosal healing in Week 8 PMS responders

12/31 (38.7%)

16/31 (51.6%)

Clinical remission in Week 8 PMS remitters

9/21 (42.9%)

10/22 (45.5%)

Corticosteroid-free remission in Week 8 PMS respondersc

4/13 (30.8%)

5/16 (31.3%)

a Adalimumab 0.6 mg/kg (maximum of 40 mg) every other week

b Adalimumab 0.6 mg/kg (maximum of 40 mg) every week

c In patients receiving concomitant corticosteroids at baseline

Note: Patients with missing values at Week 52 or who were randomized to receive re-induction or maintenance treatment were considered non-responders for Week 52 endpoints

Additional exploratory efficacy endpoints included clinical response per the Paediatric Ulcerative Colitis Activity Index (PUCAI) (defined as a decrease in PUCAI ≥ 20 points from Baseline) and clinical remission per PUCAI (defined as PUCAI < 10) at Week 8 and Week 52 (Table 33).

Table 33

Exploratory Endpoints Results per PUCAI

 

Week 8

Adalimumaba

Maximum of 160 mg at Week 0/ Placebo at Week 1

N=30

Adalimumabb,c

Maximum of 160 mg at Week 0 and Week 1

N=47

Clinical remission per PUCAI

10/30 (33.3%)

22/47 (46.8%)

Clinical response per PUCAI

15/30 (50.0%)

32/47 (68.1%)

 

Week 52

Adalimumabd

Maximum of 40 mg eow

N=31

Adalimumabe

Maximum of 40 mg ew

N=31

Clinical remission per PUCAI in Week 8 PMS responders

14/31 (45.2%)

18/31 (58.1%)

Clinical response per PUCAI in Week 8 PMS responders

18/31 (58.1%)

16/31 (51.6%)

a Adalimumab 2.4 mg/kg (maximum of 160 mg) at Week 0, placebo at Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2

b Adalimumab 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2

c Not including open-label Induction dose of adalimumab 2.4 mg/kg (maximum of 160 mg) at Week 0 and Week 1, and 1.2 mg/kg (maximum of 80 mg) at Week 2

d Adalimumab 0.6 mg/kg (maximum of 40 mg) every other week

e Adalimumab 0.6 mg/kg (maximum of 40 mg) every week

Note 1: Both induction groups received 0.6 mg/kg (maximum of 40 mg) at Week 4 and Week 6

Note 2: Patients with missing values at Week 8 were considered as not having met the endpoints

Note 3: Patients with missing values at Week 52 or who were randomized to receive reinduction or maintenance treatment were considered non-responders for Week 52 endpoints

Of the adalimumab-treated patients who received re-induction treatment during the maintenance period, 2/6 (33%) achieved clinical response per FMS at Week 52.

Quality of life

Clinically meaningful improvements from Baseline were observed in IMPACT III and the caregiver Work Productivity and Activity Impairment (WPAI) scores for the groups treated with adalimumab. Clinically meaningful increases (improvement) from Baseline in height velocity were observed for the groups treated with adalimumab, and clinically meaningful increases (improvement) from Baseline in Body Mass Index were observed for subjects on the high maintenance dose of maximum 40 mg (0.6 mg/kg) ew.

Paediatric Uveitis

The safety and efficacy of adalimumab was assessed in a randomized, double-masked, controlled study of 90 paediatric patients from 2 to < 18 years of age with active JIA-associated noninfectious anterior uveitis who were refractory to at least 12 weeks of methotrexate treatment. Patients received either placebo or 20 mg adalimumab (if < 30 kg) or 40 mg adalimumab (if ≥ 30 kg) every other week in combination with their baseline dose of methotrexate.

The primary endpoint was ‘time to treatment failure’. The criteria determining treatment failure were worsening or sustained non-improvement in ocular inflammation, partial improvement with development of sustained ocular co-morbidities or worsening of ocular co-morbidities, non-permitted use of concomitant medications, and suspension of treatment for an extended period of time.

Clinical Response

Adalimumab significantly delayed the time to treatment failure, as compared to placebo (See Figure 3, P < 0.0001 from log rank test). The median time to treatment failure was 24.1 weeks for subjects treated with placebo, whereas the median time to treatment failure was not estimable for subjects treated with adalimumab because less than one-half of these subjects experienced treatment failure. Adalimumab significantly decreased the risk of treatment failure by 75 % relative to placebo, as shown by the hazard ratio (HR = 0.25 [95 % CI: 0.12, 0.49]).

Figure 3: Kaplan-Meier Curves Summarizing Time to Treatment Failure in the Paediatric Uveitis Study has also been added- please see SPC for image.

 

Section 6.5:

Imraldi 40 mg solution for injection in pre-filled syringe

0.8 ml solution for injection in single-use pre-filled syringe (type I glass) with a stainless steel needle, a rigid needle shield, a rubber plunger (bromobutyl chlorobutyl), a plunger rod, a safe-shield body and a finger flange for patient use.

Packs of:

  • 1 pre-filled syringe, with 2 alcohol pads
  • 2 pre-filled syringes, each with 1 alcohol pad
  • 4 pre-filled syringes, each with 1 alcohol pad
  • 6 pre-filled syringes, each with 1 alcohol pad
     Imraldi 40 mg solution for injection in pre-filled pen
     
    0.8 ml solution for injection in single-use pre-filled pen for patient use containing a pre-filled syringe. The syringe inside the pen is made from type I glass with a stainless steel needle, a rigid needle shield, a rubber plunger (bromobutyl chlorobutyl).

     

 

 

Updated on 20 May 2021

File name

Imraldi IE MT NIR 40mg PFP PL May 21_1621512609.pdf

Reasons for updating

  • Change to section 6 - manufacturer
  • Change to section 6 - date of revision

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  • Name of manufacturer responsible for batch release changed from Biogen (Denmark) Manufacturing ApS to FUJIFILM Diosynth Biotechnologies Denmark ApS

Updated on 20 May 2021

File name

Imraldi IE MT NIR SPC May 21_1621512263.pdf

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

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

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Section 6.3 has been updated as shelf life has been extended from 36 to 42 months.

Updated on 08 April 2021

File name

Imraldi IE MT NIR 40mg PFP PL Mar 21_1617899350.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

The following text has been added to the 'Not Known' section of 'Possible Side Effects':

weight gain (for most patients, the weight gain was small).

Updated on 08 April 2021

File name

Imraldi IE SPC Mar 21_1617899037.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

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

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Section 4.8 Undesirable effects has been updated to add : “Weight increased2)” with frequency Not known added.

2) The mean weight change from baseline for  adalimumab ranged from 0.3 kg to 1.0 kg across adult indications compared to (minus) -0.4 kg to 0.4 kg for placebo over a treatment period of 4-6 months. Weight increase of 5-6 kg has also been observed in long-term extension studies with mean exposures of approximately 1-2 years without control group, particularly in patients with Crohn’s disease and ulcerative colitis. The mechanism behind this effect is unclear but could be associated with the anti-inflammatory effect of adalimumab.

Updated on 29 October 2020

File name

Imraldi IE PFP PL Oct 20_1603985748.pdf

Reasons for updating

  • Change to section 3 - how to take/use
  • Change to section 6 - what the product looks like and pack contents
  • Correction of spelling/typing errors

Free text change information supplied by the pharmaceutical company

The following information was added to section 3:

Paediatric population

Imraldi pre-filled syringe and pre-filled pen are only available as a 40 mg dose. Thus, it is not possible to administer Imraldi pre-filled syringe and pre-filled pen to paediatric patients that require less than a full 40 mg dose. If an alternative dose is required, other presentations offering such an option should be used.

Section 6 was updated as follows:

Name and address of the manufacturer(s) responsible for batch release

 Biogen (Denmark) Manufacturing ApS

Biogen Allé 1

3400 Hillerød

Denmark

 Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

The Netherlands

Section 7 was updated as follows:

You may see 1 or more bubbles, and that is okay

 

Updated on 29 October 2020

File name

Imraldi SPC IE MT Oct 20_1603984421.pdf

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • 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

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

Free text change information supplied by the pharmaceutical company

The following changes have been made:

Section 4.1, 4.2 and 5.1: Update of Imraldi PI to align with originator re wording for NSAIDs:

…non-steroidal anti-inflammatory drugs (NSAIDs)

non-steroidal anti-inflammatory drugs (NSAIDs)

Section 4.2- the following text has been added:

Paediatric population

Imraldi pre-filled syringe and pre-filled pen are only available as a 40 mg dose. Thus, it is not possible to administer Imraldi pre-filled syringe and pre-filled pen to paediatric patients that require less than a full 40 mg dose. If an alternative dose is required, other presentations offering such an option should be used.

Updated on 21 October 2020

File name

Imraldi IE PFP PL Sep 20_1603277598.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Section 4 has been updated to include the following:

  • Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appears as purple lesions on the skin.

Updated on 21 October 2020

File name

Imraldi IE SPC Sep 20_1603277343.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • 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

Section 4.8 has been updated to include Kaposi’s sarcoma as an undesirable effect.

EDM Updated on 31 March 2020

File name

190902_BIO_16239_IMRALDI_Patient Reminder Card_1585656803.pdf

Reasons for updating

  • Add New Doc

Updated on 07 February 2020

File name

Imraldi SPC 04.02.2020_1581094500.pdf

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • 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 to section 4.4 and section 4.6 were of a formatting nature only.

Changes to section 5.1 were as follows:

…..Uvetis

The following paragraph was added:

'Patients who completed Studies UV I and UV II were eligible to enroll in an uncontrolled long-term extension study with an originally planned duration of 78 weeks. Patients were allowed to continue on study medication beyond Week 78 until they had access to adalimumab.'...

the following paragraph has been updated from:

Of the 417 subjects included in the uncontrolled long-term extension of studies UV I and UV II, 46 subjects were regarded ineligible (e.g. developed complications secondary to diabetic retinopathy, due to cataract surgery or vitrectomy) and were excluded from the primary analysis of efficacy. Of the 371 remaining patients, 276 evaluable patients reached 78 weeks of open-label adalimumab treatment. Based on the observed data approach, 222 (80.4​​%) were in quiescence (no active inflammatory lesions, AC cell grade ≤ 0.5+, VH grade ≤ 0.5+) with a concomitant steroid dose ≤ 7.5 mg per day, and 184 (66.7​​%) were in steroid-free quiescence. BCVA was either improved or maintained (< 5 letters deterioration) in 88.4​​% of the eyes at week 78. Among the patients who discontinued the study prior to week 78, 11% discontinued due to adverse events, and 5​​% due to insufficient response to adalimumab treatment.

to:

Of the 424 subjects included in the uncontrolled long-term extension of studies UV I and UV II, 60 subjects were regarded ineligible (e.g. due to deviations or due to complications secondary to diabetic retinopathy, due to cataract surgery or vitrectomy) and were excluded from the primary analysis of efficacy. Of the 364 remaining patients, 269 evaluable patients (74%) reached 78 weeks of open-label adalimumab treatment. Based on the observed data approach, 216 (80.3%) were in quiescence (no active inflammatory lesions, AC cell grade ≤ 0.5+, VH grade ≤ 0.5+) with a concomitant steroid dose ≤ 7.5 mg per day, and 178 (66.2%) were in steroid-free quiescence. BCVA was either improved or maintained (< 5 letters deterioration) in 88.6​​% of the eyes at week 78. Data beyond Week 78 were generally consistent with these results but the number of enrolled subjects declined after this time. Overall, among the patients who discontinued the study, 18% discontinued due to adverse events, and 8​​% due to insufficient response to adalimumab treatment.

Updated on 11 September 2019

File name

Imraldi PFS PL_06.09.2019_1568196413.pdf

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 3 - dose and frequency

Free text change information supplied by the pharmaceutical company

Reference to Imraldi being only available as a 40mg pre filled syringe and pre filled pen has been deleted, as Imraldi is now available in a 40mg/0.8ml vial presentation and can be administered as a less than full 40mg dose. 

Also, section 1 has been updated as follows:

  • non-infectious uveitis affecting the back of the eye.

 

Updated on 11 September 2019

File name

Imraldi PFP PL_06.09.2019_1568196315.pdf

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 3 - dose and frequency

Free text change information supplied by the pharmaceutical company

Reference to Imraldi being only available as a 40mg pre filled syringe and pre filled pen has been deleted, as Imraldi is now available in a 40mg/0.8ml vial presentation and can be administered as a less than full 40mg dose. 

Also, section 1 has been updated as follows:

  • non-infectious uveitis affecting the back of the eye.

 

Updated on 11 September 2019

File name

Imraldi SPC PFS & PFP_06.09.2019_1568195818.pdf

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • 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

Section 4.2 of the SPC has been updated. Reference to Imraldi being only available as a 40mg pre filled syringe and pre filled pen has been deleted, as Imraldi is now available in a 40mg/0.8ml vial presentation and can be administered as a less than full 40mg dose.  

Updated on 30 April 2019

File name

Imraldi PFP PL_29.04.2019_1556633505.pdf

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 6 - date of revision

Updated on 30 April 2019

File name

Imraldi SPC 29.04.2019_1556633253.pdf

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • 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

Section 4.2: The Patient Alert card has been renamed as 'Patient Reminder Card'

Section 4.4:The Patient Alert card has been renamed as 'Patient Reminder Card'

Updated on 16 April 2019

File name

Imraldi PFP PL_12.04.2019_1555422984.pdf

Reasons for updating

  • Correction of spelling/typing errors

Updated on 16 April 2019

File name

Imraldi SPC_12.04.2019_1555423019.pdf

Reasons for updating

  • 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

The previous version of this SPC uploaded was not a consolidated version, and did not include the approved updates of the paed. uveitis indication. This version corrects the error.

Updated on 02 April 2019

File name

Imraldi PFP PL_02 Apr 2019_1554205298.pdf

Reasons for updating

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

Updated on 02 April 2019

File name

Imraldi SPC_02 Apr 2019_1554205249.pdf

Reasons for updating

  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text

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

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Section 6.4 - the storage conditions at room temperature (25C) have been extended from a maximum of 14 to a maximum of 28 days.

Updated on 11 March 2019

File name

Imraldi PFP PL_11.03.2019_1552306974.pdf

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 3 - use in children/adolescents
  • Change to further information section

Updated on 11 March 2019

File name

Imraldi SPC 11 Mar 2019_1552306499.pdf

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • 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

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

Free text change information supplied by the pharmaceutical company

- Section 4.1 has been updated to include the following text:

Paediatric Uveiti

Imraldi is indicated for the treatment of paediatric chronic non-infectious anterior uveitis in patients from 2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in whom conventional therapy is inappropriate.

 - Section 4.2 been updated to include the following text:

Paediatric uveitis

 The recommended dose of Imraldi for paediatric patients with uveitis from 2 years of age is based on body weight (Table 5). Imraldi is administered via subcutaneous injection.

 In paediatric uveitis, there is no experience in the treatment with adalimumab without concomitant treatment with methotrexate.

 

Table 5 Imraldi Dose for Paediatric Patients with Uveitis

 

Patient Weight

Dosing Regimen

< 30 kg

-

≥ 30 kg

40 mg every other week in combination with methotrexate

- Not applicable, Imraldi is only available as 40 mg pre-filled syringe and pre-filled pen

 

When Imraldi therapy is initiated, a loading dose of 40 mg for patients < 30 kg or 80 mg for patients ≥ 30 kg may be administered one week prior to the start of maintenance therapy. No clinical data are available on the use of an adalimumab loading dose in children < 6 years of age (see section 5.2).

 There is no relevant use of adalimumab in children aged less than 2 years in this indication.

 It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a yearly basis (see section 5.1).

 - Section 4.8 been updated to include the following text:

No malignancies were observed in 60 paediatric patients with an exposure of 58.4 patient years during an adalimumab trial in paediatric patients with uveitis.

  - Section 5.1 been updated to include the following text:

Paediatric Uveitis

 The safety and efficacy of adalimumab was assessed in a randomized, double-masked, controlled study of 90 paediatric patients from 2 to < 18 years of age with active JIA-associated noninfectious anterior uveitis who were refractory to at least 12 weeks of methotrexate treatment. Patients received either placebo or 20 mg adalimumab (if < 30 kg) or 40 mg adalimumab (if ≥ 30 kg) every other week in combination with their baseline dose of methotrexate.

 The primary endpoint was ‘time to treatment failure’. The criteria determining treatment failure were worsening or sustained non-improvement in ocular inflammation, partial improvement with development of sustained ocular co-morbidities or worsening of ocular co-morbidities, non-permitted use of concomitant medications, and suspension of treatment for an extended period of time.

 Clinical Response

 Adalimumab significantly delayed the time to treatment failure, as compared to placebo (See Figure 3, P < 0.0001 from log rank test). The median time to treatment failure was 24.1 weeks for subjects treated with placebo, whereas the median time to treatment failure was not estimable for subjects treated with adalimumab because less than one-half of these subjects experienced treatment failure. Adalimumab significantly decreased the risk of treatment failure by 75 % relative to placebo, as shown by the hazard ratio (HR = 0.25 [95 % CI:  0.12, 0.49]).

  -Section 5.2 been updated to include the following text:

Adalimumab exposure in paediatric uveitis patients was predicted using population pharmacokinetic modelling and simulation based on cross-indication pharmacokinetics in other paediatric patients (paediatric psoriasis, juvenile idiopathic arthritis, paediatric Crohn’s disease, and enthesitis-related arthritis). No clinical exposure data are available on the use of a loading dose in children < 6 years. The predicted exposures indicate that in the absence of methotrexate, a loading dose may lead to an initial increase in systemic exposure.

 

Updated on 27 November 2018

File name

Imraldi pre-filled pen PL_16.11.2018_1543338736.pdf

Reasons for updating

  • New PIL for new product

Updated on 27 November 2018

File name

Imraldi SPC_16.11.2018_1543338714.pdf

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

New product.