Positive results for fenebrutinib in patients with biologic DMARD refractory RA
medwireNews: Fenebrutinib has shown efficacy for reducing rheumatoid arthritis (RA) activity in patients with an inadequate response to either methotrexate or tumor necrosis factor (TNF) inhibitors, phase II study findings show.
Presenting the findings at the EULAR 2019 congress in Madrid, Spain, Stanley Cohen (Metroplex Clinical Research Center, Dallas, Texas, USA) reported a significantly superior ACR50 response rate after 12 weeks of treatment with the Bruton’s tyrosine kinase (BTK) inhibitor compared with placebo in two cohorts of patients with moderate-to-severe RA.
The first cohort comprised patients who had an inadequate response to methotrexate or other DMARDs and were randomly assigned to take fenebrutinib at a dose of 50 mg/day, 150 mg/day, or 200 mg (n=259) twice a day versus placebo (n=110) and 40 mg injections of adalimumab every 2 weeks (n=111).
The ACR50 response rate was significantly higher among patients taking fenebrutinib at doses of 150 mg (n=109) and 200 mg (n=110) than among placebo-treated patients, at 27.5% and 34.5% versus 14.5%, respectively. And it was similar to the 36% rate seen among the patients given adalimumab, Cohen noted.
The second cohort included 48 RA patients who had not responded to TNF inhibitors who were randomly assigned to receive fenebrutinib 200 mg twice a day and 50 patients assigned to placebo.
Again fenebrutinib proved superior to placebo, with ACR50 response rates at 12 weeks of 25% versus 12%.
A similar significant benefit with fenebrutinib over placebo was seen for the secondary endpoints of ACR20 response at the highest 200 mg fenebrutinib dose, ACR70 response at all doses, and change in DAS28-CRP at all doses.
Cohen reported that the rate of adverse events was similar across the treatment groups and serious adverse events were few.
He added that among patients in the methotrexate group, there was “a slight numerical increase” in serious adverse events in the fenebrutinib 200 mg group, at three to one in the placebo group, “which primarily was due to grade 3 [liver function test] elevation but this did reverse with discontinuation of the drug.”
He also remarked that “in contrast to other kinase inhibitors, there were no changes in hemoglobin/hematocrit, white blood cells, platelets, neutrophils, or monocytes,” and there were minimal dose-dependent increases in serum creatinine levels, with no cases of renal insufficiency.
Cohen said the study “provides clinical evidence to support the rationale for evaluation of BTK inhibition in patients with active rheumatoid arthritis.”
And he believes that “additional evaluation of fenebrutinib in patients with biologic DMARD refractory RA, who represent a population that we struggle with in clinic, needs to be conducted and would be very useful to further characterize the safety and efficacy profile of fenebrutinib.”
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