Clinical Pearls & Morning Reports
Published July 7, 2021
Warren et al. randomly assigned patients with moderate-to-severe plaque psoriasis in a 1:1:1 ratio to receive subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at a dose of 320 mg every 4 weeks for 16 weeks, then every 8 weeks for weeks 16 to 56; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56. Read the NEJM Original Article here.
Q: Name some inflammatory cytokines that are known to play a role in the pathogenesis of psoriasis.
A: The proinflammatory cytokines interleukin-12 and tumor necrosis factor (TNF) play roles in the pathogenesis of psoriasis. Additional involvement of interleukin-17 and interleukin-23 in the pathogenesis of this condition has been identified; however, TNF inhibitors remain a mainstay treatment for psoriasis. The cytokines interleukin-17A and interleukin-17F form homodimers (interleukin-17A/17A and interleukin-17F/17F) and heterodimers (interleukin-17A/17F) and act synergistically with TNF in stimulating inflammation. Some evidence suggests that interleukin-17A inhibition is superior to TNF inhibition in controlling the pathologic features of psoriasis.
Q: What is bimekizumab?
A: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F, which — unlike inhibitors of interleukin-17A alone — results in the inhibition of all three dimeric isoforms, including interleukin-17F/17F.
A: The primary end points were a Psoriasis Area and Severity Index (PASI) 90 response (≥90% reduction from baseline in the PASI score) at week 16 and an Investigator’s Global Assessment (IGA) score of 0 or 1 (“clear” or “almost clear,” respectively, with at least a 2-grade improvement from baseline) at week 16. Among patients receiving bimekizumab (both dose groups combined), 275 of 319 (86.2%) had a PASI 90 response (first primary end point) at week 16, as compared with 75 of 159 (47.2%) receiving adalimumab (adjusted risk difference, 39.3 percentage points; 95% confidence interval [CI], 30.9 to 47.7; P<0.001 for noninferiority and superiority). A total of 272 of 319 patients (85.3%) in the combined bimekizumab groups had an IGA score of 0 or 1 at week 16 (second primary end point), as compared with 91 of 159 (57.2%) in the adalimumab group (adjusted risk difference, 28.2 percentage points; 95% CI, 19.7 to 36.7; P<0.001 for noninferiority and superiority).
A: Oral candidiasis and diarrhea were more common with bimekizumab than with adalimumab. Most cases of oral candidiasis were mild to moderate in intensity (97%). The incidence of oral candidiasis was similar to that reported in other phase 3 trials of bimekizumab and is presumed to be the result of the role of interleukin-17 in host defense against candida at the oral mucosa.