Cimzia (certolizumab pegol) - 6 indications

Scroll down for information on each indication:

• Crohn's disease; approved 04/01/2008
• Rheumatoid arthritis; approved 05/01/2009
• Active psoriatic arthritis; approved 09/01/2013
• Active ankylosing spondylitis; approved 10/01/2013
• Moderate-to-severe plaque psoriasis; approved 05/01/2018
• Non-radiographic axial spondyloarthritis; approved 03/01/2019

General Information

Cimzia (certolizumab pegol) is a tumor necrosis factor (TNF) blocker.

Cimzia is specifically indicated for the following conditions:

• reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
• adults with moderately to severely active rheumatoid arthritis (RA)
• adult patients with active psoriatic arthritis (PsA).
• adults with active ankylosing spondylitis (AS). 
• adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy
• adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation

Cimzia is supplied as an injection for subcutaneous administration. Scroll down for specific dosing recommendations for each therapeutic condition.

Mechanism of Action

Cimzia (certolizumab pegol) binds to human TNFα with a KD of 90pM. TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Certolizumab pegol selectively neutralizes TNFα but does not neutralize lymphotoxin α (TNFβ).

Side Effects

Adverse effects associated with the use of Cimzia may include, but are not limited to, the following:

• upper respiratory tract infection
• rash
• urinary tract infection

The Cimzia drug label comes with the following Black Box warning: Patients treated with Cimzia are at an increased risk of serious infections leading to hospitalization or death including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens. Cimzia should be discontinued if a patient develops a serious infection or sepsis. Perform test for latent TB; if positive, start treatment for TB prior to starting Cimzia. Monitor all patients for active TB during treatment, even if initial latent TB test is negative. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which Cimzia is a member. Cimzia is not indicated for use in pediatric patients. 

Indication 1 - Crohn's disease

approved 04/01/2008

Dosing/Administration

400 mg initially and at Weeks 2 and 4. If response occurs, follow with 400 mg every four weeks.

Clinical Trial Results

FDA approval of Cimzia was based on the results of two clinical trials. 

Study CD1
This randomized placebo-controlled study enrolled 662 subjects with active Crohn’s disease. The subjects received Cimzia (400 mg subcutaneously) or placebo administered at Weeks 0, 2, and 4 and then every four weeks to Week 24. Assessments were done at Weeks 6 and 26. Clinical response was defined as at least a 100-point reduction in CDAI score compared to baseline, and clinical remission was defined as an absolute CDAI score of 150 points or lower. At Week 6 the proportion of clinical responders was 35% in the Cimzia group compared to 27% in the placebo group. Clinical remission was seen in 22% of the Cimzia group and 17% of the placebo group; this did not reach statistical significance. At Week 26 the proportion of clinical responders was 37% in the Cimzia arm and 27% in the placebo arm and clinical remission was seen in 29% of the Cimzia arm and 18% of the placebo arm.

Study CD2
All the subjects who entered this randomized treatment-withdrawal study were initially treated with Cimzia 400 mg at Weeks 0, 2, and 4. They were subsequently assessed for clinical response at Week 6 (as defined by at least a 100-point reduction in CDAI score). At Week 6, a group of 428 clinical responders were randomized to receive either Cimzia 400 mg or placebo, every four weeks starting at Week 8, as maintenance therapy through Week 24. Non-responders were withdrawn from the study. Final evaluation was based on the CDAI score at Week 26. At Week 26 the proportion of clinical responders in the Cimzia 400 mg x3 + Placebo group was 36% compared to 63% in the Cimzia 400 mg arm. Clinical remission was seen in 29% of the Cimzia/placebo arm and 48% in the Cimzia arm.

Indication 2 - Rheumatoid arthritis

approved 05/01/2009

Dosing/Administration

400 mg initially and at Weeks 2 and 4, followed by 200 mg every other week; for maintenance dosing, 400 mg every 4 weeks can be considered

Clinical Trial Results

The FDA approval of Cimzia for rheumatoid arthritis was based on four randomized, placebo-controlled, double-blind studies (RA-I, RA-II, RA-III, and RA-IV ). 

Study RA-I and Study RA-II
These studies evaluated subjects who had received MTX for at least 6 months prior to study medication, but had an incomplete response to MTX alone. Subjects were treated with a loading dose of 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either 200 mg or 400 mg of CIMZIA or placebo every other week, in combination with MTX for 52 weeks in Study RA-I and for 24 weeks in Study RA-II. Efficacy was based on ACR20 response at Week 24 (RA-I and RA-II) and modified Total Sharp Score (mTSS) at Week 52 (RA-I). An open-label extension follow-up study enrolled 846 patients who received 400 mg of Cimzia every other week.

Study RA-III
This study enrolled 247 subjects who had active disease despite receiving MTX for at least 6 months prior to study enrollment. Subjects received 400 mg of Cimzia every four weeks for 24 weeks without a prior loading dose. They were evaluated for signs and symptoms of RA using the ACR20 at Week 24.

Study RA-IV
This monotherapy study enrolled 220 subjects who had failed at least one DMARD use prior to receiving Cimzia. Subjects were treated with Cimzia 400 mg or placebo every 4 weeks for 24 weeks. They were evaluated for signs and symptoms of active RA using the ACR20 at Week 24.

In all studies, Cimzia-treated patients had higher ACR20, 50 and 70 response rates at 6 months compared to placebo-treated patients. Over the one-year Study RA-I, 13% of Cimzia-treated patients achieved a major clinical response, defined as achieving an ACR70 response over a continuous 6-month period, compared to 1% of placebo-treated patients. In all studies, Cimzia led to greater improvements from baseline than placebo in physical function as assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 (RA-II, RA-III and RA-IV) and at Week 52 (RA-I).

Indication 3 - Active psoriatic arthritis

approved 09/01/2013

Dosing/Administration

400 mg initially and at week 2 and 4, followed by 200 mg every other week; for maintenance dosing, 400 mg every 4 weeks can be considered

Clinical Trial Results

The FDA approval of Cimzia for psoriatic arthritis was based on a multi-center, randomized, double-blind, placebo controlled trial (PsA001) in 409 patients aged 18 years and older with active psoriatic arthritis despite DMARD therapy. Patients in this study had ≥ 3 swollen and tender joints and adult-onset PsA of at least 6 months’ duration as defined by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria, and increased acute phase reactants. Patients had failed one or more DMARDs. Previous treatment with one anti-TNF biologic therapy was allowed. Patients received a loading dose of Cimzia 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either Cimzia 200 mg every other week or Cimzia 400 mg every 4 weeks or placebo every other week. Patients were evaluated for signs and symptoms and structural damage using the ACR20 response at Week 12 and modified Total Sharp Score (mTSS) at Week 24. ACR20 at Week 12 was reached by 24% of the placebo arm, 58% of the Cimzia 200 mg every other week and 52% of the Cimzia every 4 weeks treatment arms. Patients treated with Cimzia 200 mg every other week demonstrated greater reduction in radiographic progression compared with placebo-treated patients at Week 24 as measured by change from baseline in total modified mTSS Score (estimated mean score was 0.18 in the placebo group compared with -0.02 in the Cimzia 200 mg group). Patients treated with Cimzia 400 mg every four weeks did not demonstrate greater inhibition of radiographic progression compared with placebo-treated patients at Week 24. 

Indication 4 - Active ankylosing spondylitis

approved 10/01/2013

Dosing/Administration

400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every other week or 400 mg every 4 weeks

Clinical Trial Results

The FDA approval of Cimzia for active ankylosing spondylitis was based on one multicenter, randomized, double-blind, placebo controlled study (AS-1) in 325 patients ≥18 years of age with adult-onset active axial spondyloarthritis for at least 3 months. 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). Patients must have been intolerant to or had an inadequate response to at least one NSAID. Patients were treated with a loading dose of Cimzia 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either 200 mg of Cimzia every 2 weeks or 400 mg of Cimzia every 4 weeks or placebo. Concomitant NSAIDs were received by 91% of the AS patients. The primary efficacy variable was the proportion of patients achieving an ASAS20 response at Week 12. A greater proportion of patients treated with Cimzia 200 mg every 2 weeks or 400 mg every 4 weeks achieved ASAS 20 response compared to patients treated with placebo. Responses were similar in patients receiving Cimzia 200 mg every 2 weeks and 400 mg every 4 weeks. 

Indication 5 - Moderate-to-severe plaque psoriasis

approved 05/01/2018

Dosing/Administration

400 mg (given as 2 subcutaneous injections of 200 mg each) every other week. For some patients (with body weight ≤ 90 kg), a dose of 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at Weeks 2 and 4, followed by 200 mg every other week may be considered

Clinical Trial Results

The FDA approval of Cimzia for moderate to severe plaque psoriasis was based on three multicenter, randomized, double-blind studies: PS-1, PS-2 and PS-3 which enrolled subjects 18 years of age or older with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy. Subjects had a Physician Global Assessment (PGA) of ≥ 3 (“moderate”) on a 5-category scale of overall disease severity, a Psoriasis Area and Severity Index (PASI) score ≥ 12, and body surface area (BSA) involvement of ≥ 10%.

Studies PS-1 (234 subjects) and PS-2 (227 subjects) randomized subjects to placebo, Cimzia 200 mg every other week (following a loading dose of Cimzia 400 mg at Weeks 0, 2, and 4), or Cimzia 400 mg every other week. Studies PS-1 and PS-2 assessed the co-primary endpoints of the proportion of patients who achieved a PASI 75 and PGA of “clear” or “almost clear” with at least a 2-point improvement at Week 16. In Study PS-1 PASI 75 was reached by 7% of patients in the placebo arm, 65% of patients in the 200 mg arm; 75% in the 400 mg arm at Week 16. The PGA goal was reached by 4% of the placebo arm, 45% of the patients in the 200 mg arm and 55% in the 400 mg arm. In Study PS-2 PASI 75 was reached by 13% of patients in the placebo arm, 81% of patients in the 200 mg arm; 82% in the 400 mg arm at Week 16. The PGA goal was reached by 3% of the placebo arm, 61% of the patients in the 200 mg arm and 65% in the 400 mg arm.

Study PS-3 randomized 559 subjects to receive placebo, Cimzia 200 mg every other week (following a loading dose of Cimzia 400 mg at Weeks 0, 2, and 4), Cimzia 400 mg every other week up to Week 16, or a biologic comparator (up to Week 12). Study PS-3 assessed the proportion of patients who achieved a PASI 75 at Week 12 as the primary endpoint. PASI 75 at Week 12 was reached by 4%, 69% and 75% of patients in the placebo, Cimzia 200 mg and Cimzia 400 mg arms, respectively.

Indication 6 - Non-radiographic axial spondyloarthritis

approved 03/01/2019

Dosing/Administration

400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every other week or 400 mg every 4 weeks

Clinical Trial Results

This FDA approval of Cimzia for non-radiographic axial spondyloarthritis was based on data from C-AXSPAND, a Phase 3, multi-center, double-blind, placebo-controlled 52-week study that randomized 317 adult patients to receive either Cimzia or placebo plus common background medications, which included NSAIDs, corticosteroids, analgesics and slow-acting anti-rheumatic drugs. The study met its primary endpoint, with 47.2% of patients treated with Cimzia demonstrating major improvement response in Ankylosing Spondylitis Disease Activity Score (ASDAS-MI) at week 52, compared to 7.0% of patients treated with placebo.