medwireNews: Rheumatoid arthritis (RA) patients with an inadequate response or intolerance to biologic DMARDs who are treated with the selective Janus kinase (JAK)1 inhibitor filgotinib are more likely to achieve a clinical response than those given placebo, phase III trial results suggest.
As reported in JAMA, ACR20 response rates after 12 weeks of treatment were significantly higher among the 147 patients randomly assigned to receive filgotinib 200 mg/day and the 153 given filgotinib 100 mg/day compared with the 148 participants given placebo, at 66.0% and 57.5% versus 31.1%, respectively.
Mark Genovese (Stanford University School of Medicine, Palo Alto, California, USA) and FINCH 2 co-investigators say that improvements in ACR20 response rates with filgotinib versus placebo “were evident at week 2 (earliest assessment), and responses were maintained or improved over 24 weeks, reflecting a time course similar to that seen with other JAK inhibitors.”
Click through for a guide to the trials of JAK inhibitors in patients with rheumatoid arthritis
Individuals given filgotinib 200 mg or 100 mg also experienced significantly greater improvements in HAQ-DI score from baseline to week 12 than those given placebo (0.55 and 0.48 vs 0.23-point decreases, respectively), and were significantly more likely to achieve a DAS28-CRP score of 3.2 points or lower (40.8 and 37.3 vs 15.5%, respectively). There were no radiographic endpoints in the FINCH 2 trial.
The researchers note that the majority (75–78%) of patients in all three groups had received no more than two different biologic agents before participating in the trial, and 82% overall received concomitant methotrexate in addition to the study drug.
Genovese and colleagues report that there was “little difference” in adverse event (AE) rates between the treatment groups, but caution that the trial “was not powered to make statistical comparisons of adverse events among the randomized groups.”
Over 24 weeks of follow-up, treatment-emergent AEs occurred in 69.4% of patients given filgotinib 200 mg, 63.4% of those given the 100 mg dose, and 67.6% of those in the placebo group.
Infections were reported in 36.1%, 34.0%, and 25.7% of patients in the 200 mg, 100 mg, and placebo groups, respectively, while serious infections affected a corresponding 0.7%, 2.0%, and 1.4% of patients. Four cases of uncomplicated herpes zoster occurred among filgotinib-treated patients, and one participant in the filgotinib 200 mg group experienced grade 2 retinal vein occlusion.
Commenting on these findings in an accompanying editorial, Jasvinder Singh (University of Alabama at Birmingham, USA) says that “[c]orrelating JAK subtype inhibition with specific harms, such as thrombosis, herpes zoster, and other risks, is challenging at present.”
He adds: “Mechanistic and large postmarketing clinical studies of each agent are needed to better understand these potential harms and adverse events and the subpopulations of patients with RA at highest risk of specific harms, considering their comorbidity profile and concomitant medications.”
Nevertheless, he believes that the FINCH 2 trial “provides pivotal data on the efficacy of filgotinib […] in RA refractory to biologic DMARDs.” He notes that “[t]he potential availability of other JAK inhibitor drugs, such as filgotinib, peficitinib, and upadacitinib, in the future,” in addition to the approved agents tofacitinib and baricitinib, “will further expand the choices within this class of medications.”
And Singh concludes: “Head-to-head comparison of filgotinib with other JAK inhibitors, biologic DMARDs, and triple conventional DMARD therapy will further define the most appropriate use of filgotinib for patients with RA by examining the comparative efficacy and safety.”
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