Dose escalation of certolizumab pegol from 200 mg to 400 mg every other week provides no additional efficacy in rheumatoid arthritis: an analysis of individual patient-level data

Abstract

Objective: To determine whether certolizumab pegol (CZP) dosage escalation from 200 mg to 400 mg every other week benefits some patients with rheumatoid arthritis (RA).

Methods: In the extension of the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) study into an open-label study, all patients received CZP 400 mg every other week in combination with methotrexate (MTX). Before the open-label phase of the study, patients had received CZP 200 mg or 400 mg every other week, or placebo every other week, as add-on therapy to MTX. The open-label study included those who had completed the RAPID 1 study (to week 52) and also those who had been withdrawn from the study (at week 16, due to inadequate response). At 12 weeks and 48 weeks after enrollment in the open-label study, changes in the Disease Activity Score in 28 joints (DAS28) were compared in dose-escalation patients (200 mg increased to 400 mg every other week) versus stable-dosage patients (400 mg every other week), using cumulative probability plots of individual patient-level data.

Results: In the group of patients who had completed the RAPID 1 study and had moderate or severe disease activity at entry into the open-label study, and in those who had been withdrawn early from the RAPID 1 study, the median DAS28 improvements 12 weeks after enrollment into the open-label study were similar in the dose-escalation and stable-dose groups. Individual patient-level data revealed no greater likelihood of response in the group of patients who received an increased dosage of CZP versus those in whom a stable dosage was maintained, whether they had completed the RAPID 1 study or had been withdrawn early.

Conclusion: Although patient heterogeneity in clinical settings is acknowledged, the present results indicate that increasing the dose of CZP from 200 mg to 400 mg offers little additional benefit in RA, even for selected patients.

Trial registration: ClinicalTrials.gov NCT00152386 NCT00175877.