Background/Purpose: The efficacy and safety of certolizumab pegol (CZP) in the treatment of adult patients with moderate to severe rheumatoid arthritis (RA), when administered either in combination with methotrexate (MTX) or as monotherapy, has been previously shown in several controlled clinical trials. However, a detailed assessment of CZP in combination with a wide range of non-biologic disease-modifying drugs (nbDMARDs) used in clinical practice compared to switching to monotherapy after achieving a response when added to nbDMARD(s) is lacking. The objective of this trial was to compare the effectiveness and tolerability of CZP given as add-on to nbDMARDs, including MTX and others, or as monotherapy after achieving a DAS28(ESR) improvement of ≥1.2.

  Methods: RA patients who had CZP added in clinical practice to their existing DMARD regimen due to inadequate response to their nbDMARD(s) were eligible. At 3 or 6 months, those patients who achieved a change in DAS28 of ≥1.2 were randomized to continue combination therapy (Combination group) or withdraw nbDMARD therapy (Monotherapy group) and be followed up to 18 months. A sample size of 125 randomized patients was estimated to be required to have 100 randomized (50 per group) to detect a difference of 15% in response.  

Results: A total of 124 patients were enrolled, of whom 81 were randomized to continue combination therapy (n=37) or withdraw nbDMARDs (n=44). No significant differences were observed between-groups in baseline age (58.4 vs. 54.2 years), gender (84% vs. 71% female), race (87% vs. 91% Caucasian), rheumatoid factor status (58% vs. 60% positive), or prior biologic experience (16% vs. 11%).

At 18 months, upon adjusting for baseline scores, similar improvements were observed between groups in DAS28(ESR) (-2.1 vs. -2.1) (Figure 1). Furthermore, the odds of achieving DAS28 LDA (OR [95%CI]: 1.08 [0.36-3.23]), ΔDAS28≥1.2 (1.59 [0.51-4.89]), LDA and/or ΔDAS28≥1.2 (1.36 [0.43-4.36), and remission (1.00 [0.35-2.89) were not different between the Combination and Monotherapy groups. Similarly, no differences were observed between groups at 12 months of treatment with respect to these outcomes.

Conclusion: The results suggest that, among RA patients achieving a therapeutic response when on combination therapy with certolizumab pegol and nbDMARDs, nbDMARDs could be withdrawn without significant impact on treatment effectiveness over the next year.

Figure 1. DAS28 (ESR) Scores

Figure 2. Proportions of Patients Achieving LDA and Remission at Month 18