Background Patients (pts) with rheumatoid arthritis (RA) often experience comorbidities that may affect efficacy and safety when treated with different drugs.1 Baricitinib (BARI) is a selective inhibitor of Janus kinase2,3 1 and 2 that improves disease activity in pts with RA with an acceptable safety profile.4–6
Objectives To investigate the effect of selected comorbidities on safety and efficacy outcomes in pts treated with BARI.
Methods Pts were selected for this post hoc analysis on the basis of historical or ongoing conditions defined by Medical Dictionary for Regulatory Activities and divided by the following comorbidity subgroups: depression, osteoporosis, hepatic disorders, and previous cardiovascular events. Efficacy outcomes included 20% and 50% improvement in American College of Rheumatology 20 Response (ACR20) and American College of Rheumatology 50 Response (ACR50) criteria, respectively; the proportion of pts who achieved a Disease Activity Score for 28-joint count using high-sensitivity C-reactive protein (DAS28-hsCRP) score ≤3.2; and change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at week 12. Pts who had an inadequate response (IR) to conventional disease-modifying antirheumatic drugs (cDMARDS) from 5 studies with BARI 4 mg and placebo (PBO) were included in efficacy analyses (N=1684) and safety analyses (N=1683). The interaction of comorbidity by treatment was analysed using logistic regression or analysis of variance modelling. Interaction tests were performed within each comorbidity subgroup, and the effect size in pts with and without the comorbidity was analysed.
Results Pts in the efficacy set had similar baseline demographic and disease-activity characteristics across treatments within each comorbidity subgroup. The presence of a comorbid condition did not affect the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (AE), discontinuations, or deaths caused by AEs for BARI 4 mg vs PBO (Table 1). The most common TEAEs across the subgroups for BARI and PBO were nasopharyngitis and upper respiratory tract infection. For cDMARD-IR pts, change from baseline for each comorbidity subgroup for ACR20, ACR50, DAS28-hsCRP ≤3.2 response, and HAQ-DI was higher for BARI 4 mg compared with PBO. Within each comorbidity subgroup, BARI responses compared with PBO were similar (interaction P >0.1) (Table 2).
Conclusions Treatment with BARI 4 mg showed similar effect in selected comorbidity subgroups with depression, osteoporosis, cardiovascular events, and hepatic impairment for efficacy and safety. No trends were noted for pts in each comorbidity subgroup for increased risk of events after treatment with BARI 4 mg compared with PBO.
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Disclosure of Interest B. Combe Grant/research support from: Pfizer, Roche, UCB, Consultant for: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: BMS, MSD, Pfizer, Roche, Regeneron, UCB, A. Balsa Consultant for: Eli Lilly & Company, P. Sarzi-Puttini Grant/research support from: Eli Lilly & Company, Speakers bureau: Eli Lilly & Company, H.-P. Tony Consultant for: Eli Lilly & Company, I. de Torre Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, V. Rogai: None declared, F. Durand Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, A. Jahangir Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Witt Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, J. Zhong Consultant for: Eli Lilly & Company, M. Dougados Grant/research support from: Lilly, Pfizer, UCB, Merck, BMS, Roche, Abbvie, Consultant for: Lilly, Pfizer, UCB, Merck, BMS, Roche, Abbvie