medwireNews: Treatment with the Janus kinase (JAK)1 inhibitor filgotinib or the spleen tyrosine kinase (SYK) inhibitor lanraplenib does not significantly improve outcomes for people with cutaneous lupus erythematosus (CLE), indicate phase 2 study results.
However, subgroup analyses suggest that filgotinib may warrant further investigation in certain patient populations, say Victoria Werth (University of Pennsylvania, Philadelphia, USA) and co-investigators.
The trial included 45 participants with moderate-to-severe active subacute or chronic CLE and an inadequate response or intolerance to at least one prior treatment who were randomly assigned to receive once-daily treatment with filgotinib 200 mg, lanraplenib 30 mg, or placebo. The average baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score was 17.6 points.
“Given the predominance of lupus in women and ongoing studies to assess the effect of [filgotinib] on semen parameters at the time of starting this study […], recruitment was restricted to female patients aged 18–75 years,” explain Werth et al.
Continued treatment with stable doses of permissible background therapies was allowed during the study; 60.0% of participants were on antimalarials, while 24.4% were taking systemic corticosteroids and 17.8% immunosuppressants.
As reported in Rheumatology, the change in CLASI-A score from baseline to week 12 was not significantly different among participants treated with filgotinib or lanraplenib versus those given placebo, with least squares mean reductions of 8.7 and 4.5 versus 5.5 points, respectively.
Similarly, there were no significant between-group differences in the proportion of participants achieving at least a 5-point improvement in CLASI-A score, with 68.8%, 56.3%, and 50.0% of people in the filgotinib, lanraplenib, and placebo groups, respectively, meeting this endpoint.
Werth and team suggest that a number of possible reasons could explain the lack of significant benefits seen with JAK or SYK inhibition, including lack of efficacy, small participant numbers, and “unexpectedly high” response rates in the placebo arm.
However, they point out that there was a nonsignificant trend toward improvements in outcomes with filgotinib versus placebo, particularly in subgroups of patients with more severe disease at baseline, such as those with concurrent systemic lupus erythematosus (n=16), CLASI-A scores of 15 points or higher (n=22), and those taking systemic corticosteroids (n=11).
“Despite [the trial] limitations and the inability to achieve the primary endpoint, these results collectively suggest that JAK1 inhibition with [filgotinib] in CLE warrants further investigation while SYK inhibition does not,” conclude the investigators.
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