Two dosing regimens of certolizumab pegol in patients with active rheumatoid arthritis.

OBJECTIVE: To investigate clinical efficacy and safety of 2 certolizumab pegol (CZP) maintenance dosing regimens plus methotrexate (MTX) in active rheumatoid arthritis (RA) patients achieving the American College of Rheumatology 20% improvement criteria (ACR20) after the CZP 200 mg every 2 weeks open-label run-in period. METHODS: DOSEFLEX (dosing flexibility) was a double-blind, placebo-controlled randomized study with an open-label run-in phase. During the run-in phase, all patients received CZP 400 mg (weeks 0, 2, and 4) and 200 mg every 2 weeks to week 16. Week 16 ACR20 responders were randomized 1:1:1 at week 18 to CZP 200 mg every 2 weeks, 400 mg every 4 weeks, or placebo. RESULTS: A total of 209 (of 333) patients were randomized at week 18 (CZP: 200 mg, n = 70; 400 mg, n = 70; placebo, n = 69). Groups had similar baseline characteristics (week 0). Week 34 ACR20 response rates were comparable between the CZP 200 mg every 2 weeks and the 400 mg every 4 weeks groups (67.1% versus 65.2%), which was significantly higher than placebo (44.9%; P = 0.009 and P = 0.017). ACR50/70 and remission criteria were met more frequently in CZP groups than placebo at week 34, with similar responses between anti-tumor necrosis factor-experienced and naive patients. Improvements from baseline Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and Health Assessment Questionnaire disability index scores were maintained in CZP groups from week 16 to 34 while worsening on placebo. Adverse event (AE) rates in the double-blind phase were 62.9% versus 60.9% versus 62.3%; serious AE rates were 7.1% versus 2.9% versus 0.0% (CZP 200 mg, 400 mg, and placebo groups). CONCLUSION: In active RA patients with an incomplete MTX response, CZP 200 mg every 2 weeks and 400 mg every 4 weeks were comparable and better than placebo for maintaining clinical response to week 4 following a 16-week, open-label run-in phase.

Certolizumab pegol in rheumatoid arthritis patients with low to moderate activity: the CERTAIN double-blind, randomised, placebo-controlled trial.

OBJECTIVES: This 52-week, randomised, double-blind phase IIIb study assessed efficacy and safety of certolizumab pegol (CZP) as add-on therapy to non-biologic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with low to moderate disease activity, and stopping therapy in patients in sustained remission. METHODS: Patients were randomised 1:1 to CZP (400 mg at weeks 0, 2 and 4, then 200 mg every 2 weeks) or placebo (every 2 weeks) plus current non-biologic DMARDs. At week 24, patients who achieved the primary endpoint of Clinical Disease Activity Index (CDAI) remission at both weeks 20 and 24 stopped study treatment and continued in the study until week 52. RESULTS: Of 194 patients (CZP=96; placebo=98), >90% had moderate disease activity at baseline. Significantly more CZP patients met the primary endpoint than placebo patients (week 20 and 24 CDAI remission rates: 18.8% vs 6.1%; p≤0.05). At week 24, 63.0% vs 29.7% of CZP versus placebo patients (p<0.001) achieved LDA. Disease activity score (ESR) based on 28-joint count and Simplified Disease Activity Index remission rates were also significantly higher with CZP versus placebo (19.8% vs 3.1%; p≤0.01 and 14.6% vs 4.1%; p≤0.05). CZP patients reported improvements in physical function versus placebo (mean Health Assessment Questionnaire-Disability-Index change from baseline: CZP, -0.25 vs placebo, -0.03; p≤0.01). During the period following withdrawal of CZP or placebo, only 3/17 prior CZP patients and 2/6 prior placebo patients maintained CDAI remission until week 52, but CZP reinstitution allowed renewed improvement. Adverse and serious adverse event rates were comparable between CZP and placebo groups. CONCLUSIONS: Addition of CZP to non-biologic DMARDs is an effective treatment in RA patients with predominantly moderate disease activity, allowing low-disease activity or remission to be reached in a majority of the patients. However, the data suggest that CZP cannot be withdrawn in patients achieving remission. TRIAL REGISTRATION NUMBER: NCT00674362.