Estimating Patient-Specific Relative Benefit of Adding Biologics to Conventional Rheumatoid Arthritis Treatment: An Individual Participant Data Meta-Analysis

Current evidence remains ambiguous regarding whether biologics should be added to conventional treatment of rheumatoid arthritis for specific patients, which may cause potential overuse or treatment delay.

To estimate the benefit of adding biologics to conventional antirheumatic drugs for the treatment of rheumatoid arthritis given baseline characteristics.

Cochrane CENTRAL, Scopus, MEDLINE, and the World Health Organization International Clinical Trials Registry Platform were searched for articles published from database inception to March 2, 2022.

Randomized clinical trials comparing certolizumab plus conventional antirheumatic drugs with placebo plus conventional drugs were selected.

Individual participant data of the prespecified outcomes and covariates were acquired from the Vivli database. A 2-stage model was fitted to estimate patient-specific relative outcomes of adding certolizumab vs conventional drugs only. Stage 1 was a penalized logistic regression model to estimate the baseline expected probability of the outcome regardless of treatment using baseline characteristics. Stage 2 was a bayesian individual participant data meta-regression model to estimate the relative outcomes for a particular baseline expected probability. Patient-specific results were displayed interactively on an application based on a 2-stage model.

The primary outcome was low disease activity or remission at 3 months, defined by 3 disease activity indexes (ie, Disease Activity Score based on the evaluation of 28 joints, Clinical Disease Activity Index, or Simplified Disease Activity Index).

Individual participant data were obtained from 3790 patients (2996 female [79.1%] and 794 male [20.9%]; mean [SD] age, 52.7 [12.3] years) from 5 large randomized clinical trials for moderate to high activity rheumatoid arthritis with usable data for 22 prespecified baseline covariates. Overall, adding certolizumab was associated with a higher probability of reaching low disease activity. The odds ratio for patients with an average baseline expected probability of the outcome was 6.31 (95% credible interval, 2.22-15.25). However, the benefits differed in patients with different baseline characteristics. For example, the estimated risk difference was smaller than 10% for patients with either low or high baseline expected probability.

In this individual participant data meta-analysis, adding certolizumab was associated with more effectiveness for rheumatoid arthritis in general. However, the benefit was uncertain for patients with low or high baseline expected probability, for whom other evaluations were necessary. The interactive application displaying individual estimates may help with treatment selection.