Upadacitinib a promising treatment option in selected RA patients
The oral Janus Kinase (JAK) inhibitor upadacitinib appears to be useful in the treatment of rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), with the 15-mg dose having the most favourable risk-benefit profile, according to data from the phase IIb/III SELECT-SUNRISE study.
The findings suggest that upadacitinib is an attractive treatment option in the present population, the researchers said.
SELECT-SUNRISE randomized 197 Japanese adult RA patients (mean age, 55.2 years; 78.7 percent female) to treatment with upadacitinib at 7.5 mg (n=49), 15 mg (n=49) or 30 mg (n=50) once daily or matching placebo (n=49) for 12 weeks. All patients had previously received csDMARD therapy for ≥3 months and had been on a stable dose of csDMARDs (methotrexate, sulfasalazine, leflunomide, bucillamine or iguratimod) for ≥4 weeks prior to the first dose of study drug.
Mean disease duration of the cohort was 5.5 years, with high disease activity at baseline according to 28-joint DAS with C-reactive protein (DAS28-CRP) and Clinical Disease Activity Index (CDAI). A total of 187 patients (94.9 percent) completed 12 weeks of treatment.
The primary endpoint of a 20-percent improvement in the American College of Rheumatology (ACR) criteria (ACR20) response at week 12 occurred with significantly greater frequency on active treatment vs placebo (75.5 percent with 7.5 mg, 83.7 percent with 15 mg and 80.0 percent with 30 mg vs 42.9 percent; p<0.001), with significant differences observed as early as week 1 (31 percent, 25 percent and 34 percent vs 8 percent, respectively). [Rheumatology 2020;doi:10.1093/rheumatology/keaa084]
Likewise, significantly higher proportions of patients treated with upadacitinib met stringent responses, including ACR50, ACR70 and DAS28-CRP <2.6. The proportions were numerically higher in the 15- and 30-mg dose groups vs the 7.5-mg group, without incremental efficacy observed with the two higher doses.
Treatment with the JAK inhibitor also led to more patients achieving low-disease activity and remission, with significant differences seen between the 15- and 30-mg dose groups compared with placebo. There were parallel improvements seen in physical function and morning stiffness severity.
In terms of safety, adverse events (AEs) and infections were more common with upadacitinib vs placebo and numerically highest with the 30-mg dose. Serious and opportunistic infections and herpes zoster were the most frequently reported. None of the patients developed venous thromboembolic events.
“Based on the results of phase IIb trials with upadacitinib in RA, exposures associated with 15 mg QD and 30 mg QD were predicted to provide the optimal balance of benefit–risk in patients with moderately-to-severely active RA and were therefore selected for further evaluation in the global phase III development programme,” the researchers said.
“Further studies are needed to address the role of upadacitinib in Japanese patients who are methotrexate-naïve and those who have an inadequate response to biological DMARDs,” they added.