Literature
Clinical Pearls & Morning Reports
Published July 7, 2021
In the trial by Warren et al., how did bimekizumab compare with adalimumab in patients with plaque psoriasis?
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.
Clinical Pearls
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.
Morning Report Questions
Q: In the trial by Warren et al., how did bimekizumab compare with adalimumab in patients with plaque psoriasis?
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).
Q: Name two adverse events that were more common with bimekizumab than with adalimumab.
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.