Fenebrutinib effective against refractory rheumatoid arthritis

The Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib is safe and effective in the treatment of refractory rheumatoid arthritis (RA), with the effect comparable to that observed with adalimumab, according to the results of a phase II study.

The study included two patient cohorts, including those with inadequate response to either methotrexate (cohort 1, n=480) or tumour necrosis factor inhibitors (cohort 2, n=98). Patients in cohort 1 were randomly assigned to treatment with fenebrutinib (50 mg once daily, 150 mg once daily or 200 mg twice daily), 40 mg adalimumab every other week or placebo. Those in cohort 2 were randomized to receive fenebrutinib 200 mg twice daily or placebo. Both cohorts continued methotrexate therapy.

In cohort 1, the number of patients who achieved American College of Rheumatology 50 percent response criteria (ACR50) at week 12 was higher with fenebrutinib 150 mg once daily and 200 mg twice daily than placebo (28 percent and 35 percent vs 15 percent; p=0.017 and p=0.0003, respectively).

There were no significant differences seen between the 50-mg once daily dosing regimen and placebo (18 percent vs 15 percent; p=0.25) and between the 200-mg twice daily dosing regimen and adalimumab (35 percent vs 36 percent; p=0.81).

In cohort 2, ACR50 occurred more frequently with fenebrutinib 200 mg twice daily than with placebo (25 percent vs 12 percent; p=0.072).

The most common adverse events documented with the BTK inhibitor were nausea, headache, anaemia and upper respiratory tract infections. The drug had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Notably, fenebrutinib and adalimumab caused overlapping, distinct changes in B cell and myeloid biomarkers.

The present data support targeting both B and myeloid cells via BTK inhibition in the treatment of refractory RA, researchers said.