Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: Results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial - 16/07/18
, Joseph F. Merola, MD b, Alice B. Gottlieb, MD, PhD c, Christopher E.M. Griffiths, MD d, Nancy Cross, MD e, Luke Peterson, MS e, Christopher Cioffi, PhD f, Andrew Blauvelt, MD gAbstract |
Background |
Neutralizing interleukin (IL) 17F in addition to IL-17A might provide a more complete and specific approach to inhibiting inflammation.
Objective |
Assess the efficacy and safety of bimekizumab, a monoclonal antibody that potently and selectively neutralizes IL-17A and IL-17F, in patients with moderate-to-severe plaque psoriasis.
Methods |
Double-blinded, placebo-controlled phase 2b study (NCT02905006). Patients (randomized 1:1:1:1:1:1) received subcutaneous bimekizumab every 4 weeks at doses of 64 mg, 160 mg, 160 mg with 320 mg loading dose, 320 mg, 480 mg, or placebo. Primary endpoint was ≥90% reduction in Psoriasis Area Severity Index (PASI90) at week 12.
Results |
There was a significant (P < .0001) dose-dependent response for PASI90 (week 12); more patients achieved PASI90 in the bimekizumab groups (46.2%-79.1%) than patients in the placebo group (0%; P < .0001 all doses). Across all doses, there were significant improvements from baseline for all secondary endpoints (PASI90 week 8, PASI75 week 12, PASI100 week 12, and Investigators Global Assessment clear or almost clear weeks 8 and 12; P ≤ .0003) compared with placebo. More bimekizumab-treated patients than placebo-treated patients achieved PASI100 (week 12) (27.9%-60.0% vs 0%; P ≤ .0002 all doses). Treatment-emergent adverse events were reported by 126 of 208 (61%) bimekizumab-treated patients and 15 of 42 (36%) placebo-treated patients.
Limitations |
No active comparator.
Conclusion |
Dual neutralization of IL-17A and IL-17F with bimekizumab provided rapid and substantial clinical improvements in patients with psoriasis, with no unexpected or dose-related safety findings.
Le texte complet de cet article est disponible en PDF.Key words : anti-IL-17, anti-IL-17A, anti-IL-17F, bimekizumab, biologic therapy, clear or almost clear skin, dose ranging, efficacy, interleukin 17A, interleukin 17F, PASI90, PASI100, phase 2b, plaque psoriasis, randomized clinical trial, safety
Abbreviations used : AE, IBD, IGA, IL, IL-17RA, PASI, PASI75, PASI90, PASI100, PsA, TEAE, TNF
Plan
| Funding sources: Supported by UCB Pharma. |
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| Conflicts of interest: Dr Papp has received consultant fees from Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji, Seika Pharma, MSD, Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi/Genzyme, Takeda, UCB, and Valeant; investigator fees from Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, MSD, Merck-Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi/Genzyme, Takeda, UCB, and Valeant; speaker fees from Astellas, Celgene, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, MSD, Novartis, Pfizer, and Valeant; has participated in advisory boards for Astellas, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, MSD, Novartis, Pfizer, Regeneron, Sanofi/Genzyme, UCB, and Valeant; is a steering committee member for Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Kyowa Hakko Kirin, MSD, Merck-Serono, Novartis, Pfizer, Regeneron, Sanofi/Genzyme, and Valeant; and is a scientific officer for Kyowa Hakko Kirin. Dr Merola has received honoraria from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Samumed, and UCB. Dr Gottlieb has received consultant fees, advisory board fees, or speaker fees from AbbVie, Allergan, Beiersdorf Inc, Bristol-Myers Squibb, Celgene, Dermira, Lilly, Incyte, Janssen, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB, and Valeant; and research grants from Allergan, Incyte, Janssen, LEO, Eli Lilly and Company, and Novartis. Dr Blauvelt has received consultant fees from Eli Lilly and Company, Janssen, Regeneron, and Sanofi Genzyme; and is a scientific adviser or clinical study investigator for AbbVie, Aclaris, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira Inc, Eli Lilly and Company, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, and Vidac. Dr Griffiths has received grants and personal fees from AbbVie, Celgene, LEO, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB Pharma; grants from Sandoz; personal fees from Almirall and Galderma. Dr Griffiths has received research grants from AbbVie, Celgene, Novartis, Eli Lilly and Company, Janssen, Sandoz, Pfizer, LEO, and UCB. Mr Patterson and Dr Cioffi own stock in UCB. Dr Cross has no further conflicts to disclose. |
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| Previously presented: An abstract reporting the primary and secondary results of this clinical trial was presented at the American Academy of Dermatology annual meeting in San Diego, California, February 16-20, 2018. |
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| Reprints not available from the authors. |
Vol 79 - N° 2
P. 277 - août 2018 Retour au numéro
Article précédent
- Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT)
- Mark Lebwohl, Andrew Blauvelt, Carle Paul, Howard Sofen, Jolanta W?g?owska, Vincent Piguet, Daniel Burge, Robert Rolleri, Janice Drew, Luke Peterson, Matthias Augustin
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