Real-world single centre use of JAK inhibitors across the rheumatoid arthritis pathway

Abstract

Objectives To evaluate real-world efficacy of approved JAK inhibitors (JAKi) tofacitinib and baricitinib in a large, single-centre cohort of RA patients across the treatment pathway, including those refractory to multiple biologic drugs. Methods All RA patients, treated with tofacitinib (from time of compassionate access scheme) or baricitinib since approval in 2017 had DAS28-CRP scores and components recorded at baseline, 3 and 6 months (with retrospective data for compassionate access scheme). Efficacy was evaluated in the total cohort, each treatment group, and subgroups of number of prior biologic classes failed. Results One hundred and fifteen patients were treated with a JAKi (tofacitinib 54, baricitinib 69, 8 both); 76.4% female; mean (s.d.) age 57.3 (14.3) years. On average patients had received three previous bDMARDs; 11 (9.6%) were bDMARD naïve. Combined group baseline DAS28-CRP (s.d.) 5.62(1.14) improved by 1.49(1.44) and 1.67(1.61) at 3 and 6 months, respectively, comparable in individual JAKi groups; with 24% in at least low disease activity at 3 months. The biggest improvement was observed in the biologic-naïve group (mean DAS28-CRP improved from 5.16–2.14 after 6 months); while those with prior exposure to minimum three bDMARD classes had DAS28-CRP improvement of >1.2. Five out of 8 patients treated with both JAKi sequentially responded. Twelve patients previously unresponsive to IL-6 blockade responded to JAKi. No unexpected safety events were recorded. Two cases of venous thromboembolism were observed. Conclusion JAK inhibition is effective in a real-world population of RA patients, including in a subset of patients refractory to multiple previous bDMARDs.

Real-World Treatment Patterns and Clinical Outcomes of Baricitinib in Rheumatoid Arthritis Patients in Spain: Results of a Multicenter, Observational Study in Routine Clinical Practice (The ORBIT-RA Study)

“…This study showed that baricitinib provides remission or low disease activity and pain relief, even in Patients included in the ORBIT-RA study were predominantly older females with moderate to highly active RA before starting baricitinib treatment. Clinical and sociodemographic characteristics of these patients were reasonably aligned with those of previous observational studies conducted in Spain, Italy, and the UK (18)(19)(20)(21) in terms of gender, age, years of disease, seropositivity status, comorbidities, and disease activity scores (DAS28-ESR, SDAI and CDAI). Our study showed baseline moderate levels of disease activity scores (DAS28ESR 4.3 ± 1.1, SDAI 10.9 ± 10.3 and CDAI 23 ± 10 like other observational studies (18)(19)(20)(21) and lower than those of the clinical trials with baricitinib.…”

“…Clinical and sociodemographic characteristics of these patients were reasonably aligned with those of previous observational studies conducted in Spain, Italy, and the UK (18)(19)(20)(21) in terms of gender, age, years of disease, seropositivity status, comorbidities, and disease activity scores (DAS28-ESR, SDAI and CDAI). Our study showed baseline moderate levels of disease activity scores (DAS28ESR 4.3 ± 1.1, SDAI 10.9 ± 10.3 and CDAI 23 ± 10 like other observational studies (18)(19)(20)(21) and lower than those of the clinical trials with baricitinib. In the RA-BEAM study, the DAS28-ESR was 6.4 ± 1.0 and SDAI 40 ± 13 (14).…”

“…Regarding prescription patterns, we found that the use of baricitinib in the ORBIT-RA study followed recommendations in the SmPC. Most patients were bDMARD-IR (78%), which is quite different compared to Rosas et al's registry-based study in which 54% of patients were naı ¨ve to bDMARDs (18), supporting the great variability observed in prescription patterns in routine clinical practice (16,17,19). Treatment with baricitinib was started at 4 mg/day dose in 90.1% of patients since 2 mg daily is only indicated in patients older than 75 years, with a previous history of chronic or recurrent infections or renal impairment: explaining the use of this starting dose in only 18 patients of this cohort.…”

“…To date, limited evidence on baricitinib usage in the real world is available (18)(19)(20)(21). Two observational, retrospective, and prospective studies of 56 and 446 RA patients treated with baricitinib were conducted in Italy (20,21).…”

Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study

“…Another concern is whether the number or mode of action of prior bDMARDs or JAKi may affect the drug retention of JAKi. Although improvement in disease activity was greatest in the bDMARDs-naïve group, both BAR and TOF were effective in patients refractory to multiple bDMARDs 38 . In addition, prior use of bDMARDs did not affect the clinical efficacy of BAR 39 ; the clinical efficacy of BAR was similar regardless of previous multiple bDMARD use 40 .…”