In patients with active rheumatoid arthritis (RA) who have had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), treatment with baricitinib 4 mg demonstrated similar efficacy and safety during both placebo-controlled and long-term extension (LTE) observational periods, regardless of the presence or absence of select comorbidities. Findings from this study were published in Annals of the Rheumatic Diseases.
A post-hoc analysis was conducted to explore the effects of select comorbidities (depression, osteoporosis, and hepatic, cardiovascular, or pulmonary disorders) on the efficacy and safety of baricitinib therapy in patients with moderate to severe active RA. Data from the placebo-controlled periods of 5 studies of baricitinib (ClinicalTrials.gov identifiers: NCT01185353, NCT01469013, NCT00902486, NCT01710358, and NCT01721057) were pooled for the baricitinib 4-mg dose. Additional data on all baricitinib-treated patients with a median exposure of 2 years were derived from an ongoing, open-label, LTE study that comprised patients from phase 2 and phase 3 studies (ClinicalTrials.gov identifier: NCT01885078). Efficacy outcomes vs placebo were assessed at week 12. Safety observations vs placebo up to week 16 and during the LTE phase were summarized.
Data from a total of 1684 patients, 803 of whom were treated with baricitinib and 881 of whom received placebo, were analyzed. The mean participant age was 52.7 ± 12.1 years; only 2.3% of the patients were ≥75 years. Overall, 89.4% of the patients were receiving background methotrexate, either alone or in combination with another csDMARD. The number of patients who were receiving placebo and baricitinib 4 mg combined (with or without each comorbidity, respectively) were as follows: 133/1551 for depression, 247/1437 for osteoporosis, 424/1260 for hepatic disorders, 731/953 for cardiovascular conditions, and 166/1518 for pulmonary disorders.
Higher proportions of patients attained all clinical end points with baricitinib 4 mg compared with placebo at week 12 across all subgroups. The response rates among baricitinib-treated patients with or without each comorbidity were generally close to overall response rates, with the exception of depression, in which numerically lower response rates were observed in patients with vs those without depression.
A total of 1683 patients were included in the safety analysis set from the placebo-controlled periods (802 treated with baricitinib and 881 receiving placebo), with 235.2 and 246.9 patient-years of exposure to baricitinib 4 mg or placebo, respectively. Similar proportions of patients in each group experienced ≥1 treatment-emergent adverse events across comorbidity subgroups. The most common treatment-emergent adverse events included nasopharyngitis, upper respiratory tract infections, urinary tract infections, and bronchitis.
The use of baricitinib 4 mg was associated with similar efficacy and safety during the placebo-controlled and LTE observations study periods, regardless of the presence or absence of comorbidities, in patients with active RA.
The investigators concluded that additional studies are warranted to confirm the data in this study, which provide a hypothesis only.
Combe B, Balsa A, Sarzi-Puttini P, et al. Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib [published online March 6, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-214261