Nationwide Danish guidelines regarding rheumatoid arthritis (RA) patients initiating biologic treatment (i.e., biologic disease-modifying antirheumatic drugs [DMARDs]) are issued on an approximately annual basis. For biologics-naive patients treated with concomitant methotrexate, mandatory medications included certolizumab pegol (CZP; year 2013-2014, recommended compliance 80%), abatacept (ABA; 2014-2015, 80%), and biosimilar infliximab (CT-P13; 2015-2016, 50%). We hypothesized that these guidelines could be perceived as a surrogate randomization tool in which calendar period rather than patient-specific factors defined the choice of the biologic DMARD. We undertook this study to assess compliance with guidelines (supporting the assumption of surrogate randomization) and to compare the effectiveness of CZP, ABA, and CT-P13 in patients treated according to guidelines.
This was an observational cohort study emulating a randomized trial (using intent-to-treat analyses). RA patients compliant with the treatment guidelines were identified in DANBIO, and information on prior comorbidities was obtained by linking to national registries. Outcome measures included remission rates according to the Disease Activity Score in 28 joints (DAS28) (at 6 and 12 months) and treatment retention at 1 year, compared across treatment regimens. Comorbidity/confounder-adjusted multivariable logistic and Cox regression analyses were used.
Seven hundred seventy-six patients were included in the study (336 receiving CZP, 215 receiving ABA, 225 receiving CT-P13). Compliance with treatment guidelines was high: 70%, 65%, and 59%, respectively. Six-month DAS28 remission rates were 35%, 33%, and 42%, and 12-month rates were 35%, 31%, and 35%, respectively. Compared to CZP, adjusted odds ratios for 6- and 12-month DAS28 remission rates were 0.96 (95% confidence interval [95% CI] 0.63-1.47) and 0.74 (95% CI 0.47-1.15) for ABA and 1.38 (95% CI 0.91-2.09) and 0.96 (95% CI 0.62-1.49) for CT-P13, respectively. Adjusted hazard ratios for withdrawal (during days 0-90 and days 91-365) were 0.70 (95% CI 0.39-1.27) and 1.16 (95% CI 0.84-1.60) for ABA and 0.58 (95% CI 0.33-1.10) and 0.83 (95% CI 0.59-1.17) for CT-P13, respectively, compared to CZP.
The surrogate randomization procedure enabled head-to-head comparisons of CZP, ABA, and CT-P13. Although some differences in estimated effectiveness were observed across drugs, confidence intervals were wide and statistical significance was not reached.