Background Janus kinase (JAK) inhibitors are being evaluated for treatment of active rheumatoid arthritis (RA). Understanding their onset of action on patient reported outcomes (PROs) and clinical endpoints in RA patients (pts) is limited.
Objectives To assess onset of benefit with ABT-494, a selective JAK1 inhibitor vs placebo (PBO) in RA pts with active disease ≥3 months in 2 randomized controlled trials (RCTs) evaluating safety and efficacy of ABT-494. M13–537 (NCT02066389) included pts who were inadequate responders to methotrexate (MTX-IR) and M13–550 (NCT01960855) to tumor necrosis factor inhibitors (TNF-IR).
Methods Data were analyzed separately for each RCT in pts who received 6mg or 12mg bid ABT-494 or PBO. Analyses included cumulative assessment of PROs such as patient global assessment of disease activity (PtGA), pain Visual Analogue Scale (VAS) and Health Assessment Questionnaire Disability Index (HAQ-DI) in terms of Routine Assessment of Patient Index Data 3 (RAPID3) scores, and clinical outcomes such as DAS28 (CRP) and CDAI. To assess onset and maintenance of effect, the number of pts whose improvements met or exceeded minimal important differences (MID) RAPID3: reduction ≥3.6; DAS28: reduction ≥1.2; CDAI: reduction ≥11.0 and were calculated at weeks 2 and 12. Additionally, Kaplan-Meier (KM) analysis estimated mean time to achievement of RAPID3, DAS28 and CDAI MID. Non-responder imputation accounted for missing data.
Results In M13–537 (N=150 pts) and M13–550 (N=166 pts) RCTs, significantly more pts in ABT-494 12mg groups reported improvements ≥MID in RAPID3 vs PBO at Wk 2: 68% vs 30% and 73% vs 38%, respectively (Table). In M13–537, significantly more pts receiving ABT-494 6mg BID vs PBO (54% vs 30%) had improvements ≥MID in RAPID3. These responses were sustained throughout both trials in pts receiving 12mg ABT-494 (M13–537: 80%; M13–550: 71%). Significantly more pts achieved and maintained changes ≥MID in DAS28 in both RCTs and in CDAI in M13–550. Based on KM analyses, in M13–537, estimated mean time (±SE) to achievement of RAPID3 MID was shorter for both ABT-494 doses vs PBO (12mg: 3.9±0.5 weeks; 6mg: 3.9±0.4 weeks; PBO 6.0±0.6 weeks). Similarly, estimated mean time to these responses was shorter with both ABT-494 doses vs PBO (12mg: 3.6±0.4 weeks; 6mg: 4.9±0.6 weeks; PBO: 6.6±0.6 weeks) in M13–550, although it was underestimated due to censoring.
Conclusions Patients treated with ABT-494 showed fast clinically meaningful improvements in patient reported disease activity, pain, physical function cumulatively assessed as RAPID3, as well as clinical outcomes DAS28 and CDAI, as early as week 2 and sustained through week 12 in both MTX-IR and TNF-IR populations.
Acknowledgements Financial support for the study and medical writing support (Joann Hettasch, Fishawack Group, Conshohocken, PA) was provided by AbbVie. AbbVie participated in interpretation of data, review, and approval of the abstract. All authors contributed to development of the abstract and maintained control over final content.
Disclosure of Interest V. Strand Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, and UCB; Ad boards: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, and UCB, N. Tundia Shareholder of: AbbVie, Employee of: AbbVie, I. H. Song Shareholder of: AbbVie, Employee of: AbbVie, S. Meerwein Shareholder of: AbbVie, Employee of: AbbVie, J. Lin Shareholder of: AbbVie, Employee of: AbbVie, N. Chen Shareholder of: AbbVie, Employee of: AbbVie, A. Friedman Shareholder of: AbbVie, Employee of: AbbVie