Abstract | INTRODUCTION: As patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+ methotrexate (MTX) treatment for almost 5 years in patients with RA. METHODS: Patients who completed the 24-week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; NCT00160602), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160641). After ≥6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received ≥1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose-reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers. RESULTS: In the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4-15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was -3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non-responder imputation). Similar improvements observed in the ITT were maintained following dose-reduction. 73.2% of CZP Completers had no radiographic progression at Week 128. CONCLUSIONS: In patients with active RA despite MTX therapy, CZP was well tolerated, with no new safety signals identified. CZP provided sustained improvements in clinical outcomes for almost 5 years. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00160602 and NCT00160641 . Registered 8 September 2005.
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Authors | Josef S Smolen, Ronald van Vollenhoven, Arthur Kavanaugh, Vibeke Strand, Jiri Vencovsky, Michael Schiff, Robert Landewé, Boulos Haraoui, Catherine Arendt, Irina Mountian, David Carter, Désirée van der Heijde |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 17
Pg. 245
(Sep 10 2015)
ISSN: 1478-6362 [Electronic] England |
PMID | 26353833
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
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Chemical References |
- Antirheumatic Agents
- Certolizumab Pegol
- Methotrexate
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Topics |
- Adult
- Aged
- Antirheumatic Agents
(adverse effects, therapeutic use)
- Arthritis, Rheumatoid
(drug therapy, prevention & control)
- Certolizumab Pegol
(adverse effects, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Drug Therapy, Combination
- Female
- Humans
- Infections
(chemically induced)
- Kaplan-Meier Estimate
- Male
- Methotrexate
(adverse effects, therapeutic use)
- Middle Aged
- Time Factors
- Treatment Outcome
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