Cimzia 200 mg solution for injection in pre-filled pen

II - CCDS v5.0 - Prospective pregnancy outcomes 

II - CCDS v5.0 - Prospective pregnancy outcomes 

Update to Section 4.8 of the SPC with information relating to C-VIEW Clinical Study Report

PRAC Recommendation - Addition of Kaposi’s sarcoma as an adverse event of unknown frequency

PRAC Recommendation - Addition of Kaposi’s sarcoma as an adverse event of unknown frequency

section 4.2: additional sentence "After at least 1 year of treatment with Cimzia, in patients with sustained remission, a reduced maintenance dose of 200 mg every 4 weeks may be considered (see section 5.1)" in Axial Spondylorthritis




section 4.8: additional text "Cimzia was also studied in patients with axial spondyloarthritis (including ankylosing spondylitis and non-radiographic axial spondyloarthritis) in a clinical study for up to 96 weeks, which included a 48-week open-label run-in phase (N=736) followed by a 48-week placebo-controlled phase (N=313) for patients in sustained remission (C-OPTIMISE)." in Axial spondylorathritis




section 5.1: additional section "C-Optimise", additional figure (Graph), additional table of data; additional section under "immunogenicity". Section "Axial spondyloarthritis" moved to the end with additional study data related to ASooo6 and C-OPTIMISE; deletion of section "for all indication".




section 10: revision date changed to 07/2020

    Axial spondyloarthritis
•    The starting dose for adults with axial spondyloarthritis is 400 mg given at weeks 0, 2 and 4. 
•    This is followed by a maintenance dose of 200 mg every 2 weeks (from week 6) or 400 mg every 4 weeks (from week 8) as instructed by your physician. If you have received Cimzia for at least 1 year and respond to the medicine, your physician may prescribe a reduced maintenance dose of 200 mg every 4 weeks.
 

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.

4.8       Undesireable effects

Plaque psoriasis

Cimzia was studied in 1112 patients with psoriasis in controlled and open-label studies for up to 18 months3 years. In the Phase III program, the initial and maintenance periods were followed by a 96-week open-label treatment period (see section 5.1). The long-term safety profile of Cimzia 400 mg every 2 weeks and Cimzia 200 mg every 2 weeks were was generally similar and consistent with previous experience with Cimzia.

Tabulated list of adverse reactions

Adverse reactions reactions based primarily on experience from the placebo-controlled clinical trials and postmarketing cases at least possibly related to Cimzia are listed in Table 1 below, according to frequency and system organ class.

Description of selected adverse reactions

Infections

In the placebo-controlled clinical trials in rheumatoid arthritis, there were more new cases of serious infection in the Cimzia treatment groups (0.07 per patient-year; all doses), compared with placebo (0.02 per patient-year).

Malignancies and lymphoproliferative disorders

Excluding non-melanoma skin cancer, 9 11 malignancies including 1 case of lymphoma were observed in the Cimzia psoriasis clinical trials in which a total of 1112 patients were treated, representing 1481 2300 patient-years.

Autoimmunity

In the rheumatoid arthritis pivotal studies, for subjects who were ANA negative at baseline, 16.7% of those treated with Cimzia developed positive ANA titers, compared with 12.0% of subjects in the placebo group.

5.1      Pharmacodynamic properties

Plaque psoriasis

Patients with an inadequate response at Week 16 (PASI 50 non-responders) were eligible to receive Cimzia 400 mg every 2 weeks until Week 48 in an open-label manner for a maximum of 128 weeks.

All subjects who did not achieve a PASI 75 response at Week 16 entered an escape arm and received Cimzia 400 mg every 2 weeks in an open-label manner for a maximum of 128 weeks.

In all three studies, the blinded 48-week maintenance period was followed by a 96-week open-label treatment period for the patients who were PASI 50 responders at Week 48. All these patients, including those receiving Cimzia 400 mg every 2 weeks, started the open-label period at Cimzia 200 mg every 2 weeks.

Maintenance of response

In an integrated analysis of  CIMPASI-1 and CIMPASI-2, among patients who were PASI 75 responders at Week 16 and received Cimzia 400 mg every 2 weeks (N=134 of 175 randomised subjects) or Cimzia 200 mg every other 2 weeks (N=132 of 186 randomised subjects), the maintenance of response rates at Week 48 were was 98.0% and 87.5%, respectively. Among patients who were PGA clear or almost clear at Week 16 and received Cimzia 400 mg every 2 weeks (N=103 of 175) or Cimzia 200 mg every 2 weeks (N=95 of 186), the maintenance of response rate at Week 48 were was 85.9% and 84.3% respectively.

After an additional 96 weeks of open-label treatment (Week 144) the maintenance of response was evaluated. Twenty-one percent of all randomised subjects were lost to follow-up before Week 144. Approximately 27% of completer study subjects who entered the open-label treatment between weeks 48 to 144 on Cimzia 200 mg every 2 weeks had their dose increased to Cimzia 400 mg every 2 weeks for maintenance of response. In an analysis in which all patients with treatment failures were considered non-responders, the maintenance of response of the Cimzia 200 mg every 2 weeks treatment group, for the respective endpoint, after an additional 96 weeks of open-label therapy, was 84.5% for PASI 75 for study subjects who were responders at Week 16 and 78.4% for PGA clear or almost clear. The maintenance of response of the Cimzia 400 mg every 2 weeks treatment group, who entered the open-label period at Cimzia 200 mg every 2 weeks, was 84.7% for PASI 75 for study subjects who were responders at Week 16 and 73.1% for PGA clear or almost clear.

These response rates were based on a logistic regression model where missing data were imputed over 48 or 144 weeks, using multiple imputation (MCMC method) combined with NRI for treatment failures.

Quality of life / Patient reported outcomes

In addition, at Week 16, Cimzia treatment was associated with a greater proportion of patients achieving a DLQI score of  0 or 1 (Cimzia 400 mg every 2 weeks, 45.5% and 50.6% respectively; Cimzia 200 mg every 2 weeks, 47.4% and 46.2% respectively, versus placebo, 5.9% and 8.2% respectively).

Improvements in DLQI score were sustained or slightly decreased through Week 144.

Cimzia-treated patients reported greater improvements compared to placebo in the Hospital Anxiety and Depression Scale (HADS)-D.

Improvements in all afore mentioned outcomes were maintained through Week 48.

Plaque psoriasis
 

In the Phase III placebo- and active-controlled studies, the percentages of patients who were positive for  antibodies to Cimzia on at least one occasion during treatment up to Week 48 were 8.3 % (22/265) and  19.2% (54/281) for the Cimzia 400 mg every 2 weeks and Cimzia 200 mg every 2 weeks respectively. In CIMPASI-1 and CIMPASI-2, sixty patients were antibody positive, 27 of these patients were evaluable for neutralizing antibodies and tested positive. First occurrences of antibody positivity in the open-label treatment period were observed in 2.8% (19/668) of patients. Antibody positivity was associated with lowered drug plasma concentration and in some patients with reduced efficacy.

10.      DATE OF REVISION OF THE TEXT

{MM/YYYY}April 2020

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

In section 4.1 & 5.1: 

- additional description added

In section 4.8:

- additional clinical study data added

- additional description added

In section 5.2:

- additional clinical study data added

6.3     Shelf life

18 months. 2 years.

See also section 6.4 for shelf-life related to storage at room temperature up to a maximum of 25°C.

6.4     Special precautions for storage

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

The pre-filled syringes may be stored at room temperature (up to 25°C) for a single period of maximum 10 days with protection from light. At the end of this period the pre-filled syringes must be used or discarded.

-‘’Plaque psoriasis” information has been added in the following sections ‘’ 4.1 Therapeutic indications’’,’’ 4.2 Posology and method of administration’’, ‘’ 4.8 Undesirable effects”, 5.1 Pharmacodynamic properties’’;
-‘’Posology’’ and ‘’Latex-sensitivity’’ information has also been updated in section ’’ 4.2 Posology and method of administration’’;
-‘’Rheumatoid arthritis”, ‘’Tabulated list of adverse reactions”, ‘’Description of selected adverse reactions-Infections, Malignancies and lymphoproliferative disorders” has been updated in section ‘’4.8 Undesirable effects”;
-‘’Maintenance of response”, ‘’Quality of life / Patient reported outcomes”,’’Immunogenicity” has been updated in section ‘’5.1 Pharmacodynamic properties’’;
-‘’Distribution’’, ’’Pharmacokinetic/pharmacodynamic relationship” has been updated in section’’ 5.2 Pharmacokinetic properties’’;
- The section “6.5 Nature and contents of container’’ has been updated;
-‘’Section 10. DATE OF REVISION OF THE TEXT’’ has been updated {MM/YYYY} 06/2018.

SmPC changes: in sections 4.8 and 5.1: to add information about the long-term data, following the submission of two final study reports.