Bimekizumab confers benefits for RA

The addition of the monoclonal immunoglobulin G1 antibody bimekizumab to the anti-TNF* certolizumab pegol (CZP) led to a reduction in disease activity in rheumatoid arthritis (RA) patients with insufficient response to CZP, a study shows.

“[Our] study tested the principle of enhancing an insufficient response to anti-TNF therapy by the addition of another treatment … [We observed a] rapid decrease in disease activity [after] 12 weeks of CZP and bimekizumab,” said the researchers. This was reflected in the greater DAS28-CRP** reductions with bimekizumab vs placebo at week 20 (estimated posterior group mean change, -1.41, 95 percent credible interval [CrI], -1.72 to 1.09 vs -0.82, 95 percent CrI, -1.15 to 0.49).

Seventy-nine RA patients who had insufficient response to CZP during an 8-week, open-label, run-in phase were randomized 2:1 to receive CZP 200 mg every 2 weeks (Q2W) plus bimekizumab 240 mg loading dose followed by 120 mg Q2W or placebo from week 8 to 20. The add-ons were withdrawn by week 20. [Ann Rheum Dis 2019;78:1033-1040]

Analysis of individual DAS28-CRP components also revealed numerically greater reductions in PtGADA*** with bimekizumab vs placebo at weeks 20 and 32 (mean, -26.5 vs -13.8 [W20] and -31.0 vs -17.2 [W32]). Conversely, reductions in swollen and tender joint counts (SJC and TJC, respectively) were greater with placebo vs bimekizumab at week 20 (mean, -5.2 vs -3.9 [SJC] and -8.9 vs -6.2 [TJC]) and week 32 (mean, -5.6 vs -4.3 and -10.3 vs -6.7, respectively).

“[These] changes … suggest that improvements in the CZP-bimekizumab group may have been mostly attributable to changes in PtGADA, with little impact … on SJC or TJC,” said the researchers.

Placebo recipients continued to exhibit gradual improvement that by week 32, the DAS28-CRP remission rate was similar to the bimekizumab arm (34.8 percent vs 37.2 percent). “Further [investigation] is required to determine whether treatment with CZP-bimekizumab for 12 weeks [is] sufficient to downregulate the inflammatory response to a level that could be maintained once treatment with bimekizumab [is] withdrawn,” they said.

The incidence of TEAEs was higher with bimekizumab vs placebo (78.8 percent vs 59.3 percent), the most frequent being infections and infestations. Nonetheless, no unexpected or new safety findings were identified with dual interleukin (IL)­-17A and IL-17F inhibition, noted the researchers.

Targeting two pathways

Evidence shows that IL-17A inhibition has minimal efficacy in RA patients with insufficient response or intolerance to anti-TNFs, suggesting that inhibition of IL-17A alone is insufficient to neutralize the inflammatory response in RA. [Rheumatol Ther 2017;4:475-488; Arthritis Rheum 2017;69:1144-1153] Both IL-17A and IL-17F have been shown to interact with other cytokines to mediate chronic inflammation and share ~50 percent structural homology and overlapping but nonredundant biological functions, highlighting the potential role of IL-17F in RA. [J Immunol 2008;181:2799-2805]

The current findings mirror previous evidence showing the efficacy of bimekizumab in psoriasis and psoriatic arthritis. [Ann Rheum Dis 2018;77:523-532; J Am Acad Dermatol 2018;79:277-286].

Taken together, these data reinforce the rationale for dual IL-17A and IL-17F neutralization in immune-mediated inflammatory disease. “[Our] findings support the potential to further explore concomitant neutralization of multiple pathways in other patient populations where this treatment strategy may provide additional benefits,” said the researchers.