medwireNews: Addition of the Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib to standard care does not improve outcomes for patients with systemic lupus erythematosus (SLE), suggest findings from a phase II trial.
As outlined in a late-breaking poster presentation at the 2019 ACR/ARP Annual Meeting in Atlanta, Georgia, USA, 260 patients receiving standard treatment with corticosteroids, antimalarials, or immunosuppressive agents were randomly assigned to receive oral fenebrutinib at a dose of 150 mg once daily or 200 mg twice daily, or to receive placebo, for 48 weeks. Tapering of corticosteroids was recommended for all patients.
David Isenberg (University College London, UK) and co-investigators found that 51% of the 87 participants given fenebrutinib 150 mg/day and 52% of the 87 patients given the 200 mg twice daily dose achieved an SRI-4 response at week 48, compared with 44% of the 86 treated with placebo, a nonsignificant difference.
The proportion of patients achieving an SRI-4 response at week 48 with corticosteroid taper (≤day 1 dose, <10 mg/day prednisolone equivalent, and no escape therapy) was also comparable in the 150 mg, 200 mg, and placebo groups (51 and 45 vs 42%, respectively), as was the BICLA response rate (53 and 42 vs 41%).
However, despite this lack of efficacy, fenebrutinib resulted in “maximal inhibition of a BTK-dependent pathway biomarker at [week] 48,” reported Isenberg.
Indeed, treatment with fenebrutinib 150 mg/day and 200 mg twice daily versus placebo led to a significant reduction in levels of biomarkers including CD19+ B cells (reduction of 57.0 and 57.5 vs 0.5 cells/µL), antibodies against double-stranded DNA (38.3 and 75.7 IU/mL reduction vs 6.9 IU/mL increase), and immunoglobulin G antibodies (reduction of 1.25 and 1.56 vs 0.20 g/L).
Isenberg said that there were no new safety findings for fenebrutinib in the trial. A total of 89% of patients given fenebrutinib 150 mg/day, 77% of those given the 200 mg twice daily dose, and 76% of those in the placebo group experienced adverse events, while 8%, 19%, and 8%, respectively, experienced adverse events leading to treatment withdrawal.
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Arthritis Rheumatol 2019; 71 (suppl 10)
ACR/ARP 2019; Atlanta, Georgia, USA: 8–13 November