Humira 40mg solution for injection in pre-filled pen

Section 4.8 – Undesirable effects

• “Weight increased” is now listed in Table 7, under Investigations (Frequency: Not known). 
  
  The following corresponding information has been included in the footnotes:
  
  “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.”

Section 10 – Date of Revision of the Text

• Amended to “04/2021”

Section 5.1

Sub-section Paediatric Uveitis, Efficay Results

The statement:

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 per FMS (defined as an Mayo endoscopy score ≤ 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 Humira 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).

amended to:

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 Humira 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).

Section 4.1

The following indication has ben added:

Paediatric ulcerative colitis

Humira 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

Dosing information updated to reflect Paediatric ulcerative colitis indication

Section 4.8

The following statement has been added under "Malignancies and lymphoproliferative disorders":

"No malignancies were observed in 93 paediatric patients with an exposure of 65.3 patient years during a Humira trial in paediatric patients with ulcerative colitis. "

The following statement has been added under "Hepato-biliary events":

"In the controlled Phase 3 trial of Humira 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

The following statement has been added:

"In patients with moderately to severely active paediatric ulcerative colitis, the rate of anti-adalimumab antibody development in patients receiving adalimumab was 3%."

Information on safety and efficay  from multicenter, randomized, double-blind clinical trial included.

Section 5.2

The following information has been added:

Following the subcutaneous administration of body weight-based dosing of 0.6 mg/kg (maximum of 40 mg) every other week to paediatric patients with ulcerative colitis, the mean trough steady-state serum adalimumab concentration was 5.01±3.28 µg/ml at Week 52. For patients who received 0.6 mg/kg (maximum of 40 mg) every week, the mean (±SD) trough steady-state serum adalimumab concentration was 15.7±5.60 μg/ml at Week 52.

Section 10.0

Date of revision:  11/2020

Section 4.8 – Undesirable effects

• Addition of Kaposi’s sarcoma (frequency: not known) to Table 6

Section 10 – Date of Revision of the Text

• Amended to 08/2020

• Section 4.1 Therapeutic indications
  Editorial change
  
  Humira is indicated for the treatment of adults with severe axial spondyloarthritis without radiographic evidence of AS but with objective signs of inflammation by elevated CRP and / or MRI, who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs.
  
  amended to: 
  
  Humira is indicated for the treatment of adults with severe axial spondyloarthritis without radiographic evidence of AS but with objective signs of inflammation by elevated CRP and / or MRI, who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs).

• Section 10. Date of Revision of Text
  Amended to 11/2019

Change to section 7 - injection Humira (steps 6, 7, 8)

The following updates have been made to section 5.1 of the SmPC:

• Additional text describing enrolment into long term extension study
   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 Humira.
   

• Revision of study summary
  • Revision of subject numbers
  • Explanation that the number of enrolled subjects declined but data at later timepoints generally consistent with week 78
  • Updated overall numbers for discontinuations based on full duration of study
    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.

Date of Revision of text: updated to 05/2019

• Section 4.2 and section 4.4: “Patient Alert Card” changed to “Patient Reminder Card”.

Summary of Changes

Section  4.8

• Revised to include “lichenoid skin reaction” as a rare event under Skin and subcutaneous tissue disorders

Section 10

• Date of Revision of Text updated to 26 July 2018

Update to section 4.6 - Fertility, pregnancy and lactation