Certolizumab pegol plus methotrexate provides broad relief from the burden of rheumatoid arthritis: analysis of patient-reported outcomes from the RAPID 2 trial

Abstract

Objective: To assess the impact of certolizumab pegol (CZP) on patient-reported outcomes (PROs) in rheumatoid arthritis (RA), and to interpret these results using number needed to treat (NNT), and associations between PRO responses and longer term outcomes.

Methods: A total of 619 patients with active RA were randomised to CZP 200 or 400 mg, or placebo plus methotrexate (MTX). PROs assessed included pain, patient's global assessment of disease activity (PtGA), physical function, fatigue and health-related quality of life. Treatment impact on PROs, NNT to achieve simultaneous improvements in multiple PROs and correlations between PROs were calculated. Times to onset of improvements greater than or equal to minimum clinically important differences (MCIDs) in pain as a determinant of clinical outcomes at week 24 were compared between week 6 and 12 responders, and in patients with improvements in pain ≥ MCID at week 12 (week 12 responders/non-responders).

Results: CZP 200 and 400 mg plus MTX were associated with rapid, clinically meaningful improvements in all PROs. The NNT for subjects to report changes ≥MCID in up to five PROs was two to three, and five for all six PROs (pain, PtGA, physical function, fatigue and short-form 36-item Physical and Mental Component Summary Scores). More patients with improvements ≥MCID in pain at week 6 than those at week 12 had lower disease activity at week 24. Week 12 pain responders had better clinical outcomes at week 24 than non-responders.

Conclusions: The data demonstrate that CZP provides broad relief from the burden of RA. Trial registration number NCT00160602.

Conflict of interest statement

Competing interests VS has worked as an independent biopharmaceutical consultant in clinical development and regulatory affairs since September 1991 and is currently a consultant to various sponsors including UCB, but has not and does not now hold stock in any company. JSS serves as a consultant to UCB. RFvV serves as a consultant to UCB and has received research funding from UCB. PM serves as a consultant to UCB, received research funding from UCB and has received an honorarium for speaking for UCB. GRB serves as a consultant to UCB and has received honoraria from UCB for speaking. FH has no competing interests. DK serves as a consultant to UCB. EN is a Business & Decision Life Science consultant working for UCB. GC is a full-time employee of and holds stocks in UCB. MS serves as a consultant to UCB and has received research funding from UCB.

Figures

Figure 1

Adjusted mean change from baseline (SE) and percentage of patients reporting improvements ≥MCID in pain, PtGA, physical function, fatigue and health-related quality of life at week 24 (ITT population, LOCF). *p

Figure 2

Improvements in short-form 36-item (SF-36) domain scores (ITT population, LOCF). A. Spydergram of SF-36 domains at baseline and following treatment with CZP 200 mg. Scores were plotted from 0 (worst) to 100 (best) with demarcations along axes of the domains indicating changes of 10 points representing one to two times MCID. B. Percentage of patients reporting improvements ≥MCID in SF-36 domains at week 24; *p≤0.001; †p≤0.01. BP, bodily pain; CZP, certolizumab pegol; GH, general health; ITT, intent to treat; MCID, minimum clinically important difference; MH, mental health; MTX, methotrexate; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; VT, vitality.

Figure 3

NNTs to report improvements ≥MCIDs in one, two, three, four, five or six PROs after 24 weeks of treatment with CZP 200 mg+MTX and CZP 400 mg plus MTX. CZP, certolizumab pegol; MCID, minimum clinically important difference; NNT, number needed to treat; MTX, methotrexate; PROs, patient-reported outcomes.