P136 Efficacy and safety of olokizumab in a phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy

Abstract

Background/Aims Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6. Here we present the results of the phase III study of OKZ in anti-TNF-IR patients. Methods Patients with moderately to severely active RA who had previously failed TNF inhibitors (ClinicalTrials.gov Identifier NCT02760433/CREDO3) were randomized in a 2:2:1 ratio to receive subcutaneous (SC) injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or placebo (PBO), plus MTX. At week 16, all subjects in the PBO group were randomized in a 1:1 ratio to receive either of OKZ regimes. The primary endpoint was ACR20 response at week 12. Results 368 subjects were randomised according to the protocol and 320 patients (87%) completed the 24-week treatment period. Baseline characteristics were comparable across arms. Both regimens of OKZ were significantly better in primary endpoint: ACR20 were 60.9% (p = 0.0029 in comparison vs. PBO) in OKZ q2w, 59.6% in OKZ q2w (p = 0.0040 in comparison vs. PBO) and 40.6% in PBO. The key efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidences of treatment-emergent adverse events (TEAE) were 65.5% in OKZ q2w, 65.0% in OKZ q4w and 50.7% in PBO. Subsequent randomization of PBO arm at week 16 did not change TEAEs incidence rate per treatment group significantly: 64.3% in any OKZ q2w and 59.7% in any OKZ q4w. The majority of TEAEs in all groups were not serious and were of mild or moderate severity. Incidence of treatment-emergent serious adverse events (TESAE) were: 12 (7.0%) subjects in any OKZ q2w; 6 subjects (3.2%) in any OKZ q4w group, all in the first 16 weeks. The most frequently reported TESAEs across all treatment groups were infections and infestations: 2 (1.2%) in OKZ q2w group, 2 (1.1%) in OKZ q4w group. No opportunistic infections including active tuberculosis, major adverse cardiovascular events, gastrointestinal perforations or deaths were reported. Conclusion In this global Phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs and symptoms of RA compared to PBO plus MTX over a 24-week period. Treatment with OKZ q2w and q4w in this difficult to treat population was well tolerated and consistent with the established safety profile of anti-IL-6 agents. Disclosure E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. M. Luggen: Consultancies; Amgen, Sun Pharmaceuticals, R-Pharm International. Grants/research support; I havAbbvie, R-Pharm, Sun Pharmaceuticals, Pfizer, Novartis, Lilly, and GSK. E. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.

Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study

“…HDL, high-density lipoproteins; LDL, low-density lipoproteins; OKZ, olokizumab; PBO, placebo; q2w, every 2 weeks; q4w, every 4 weeks. Elements of these data were presented at the annual meeting of the American College of Rheumatology 202129 and the British Society of Rheumatology Conference 2021 30…”

“…Elements of these data were presented at the annual meeting of the American College of Rheumatology 2021 29 and the British Society of Rheumatology Conference 2021. 30 …”

Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study

“…Вследствие этого ОКЗ блокирует формирование итогового гексамера на молекулярном уровне, в то время как другие ингибиторы ИЛ6 предотвращают формирование димера. Преимуществом такого подхода является то, что димеры ИЛ6 и растворимого ИЛ6Р более не могут связываться с отвечающим за передачу сигнала элементом [29] Кроме того, механизм действия данного препарата также отличается от такового двух зарегистрированных ингибиторов сигнальной активности, связанной с ИЛ6, представляющих собой моноклональные антитела к его рецептору. Теоретически уровни растворимых ИЛ6Р у пациентов с РА намного превышают уровни самого этого цитокина (ИЛ6), в связи с чем для нейтрализации лиганда требуется меньшее количество моноклонального антитела, чем для воздействия на ИЛ6Р.…”

“…S T I G A T I O N SСовременная ревматология. 2023;17(2):[23][24][25][26][27][28][29][30][31][32][33][34][35][36] 33 Средняя динамика лабораторных показателей во время периода двойной слепой терапии в популяции оценки безопасности. ЛПВП -липопротеины высокой плотности; Hb -гемоглобин; ЛПНП -липопротеины низкой плотности.…”

“…ЛПВП -липопротеины высокой плотности; Hb -гемоглобин; ЛПНП -липопротеины низкой плотности. Эти данные были частично представлены на ежегодной конференции ACR в 2021 г [29]. и на конференции Британского общества ревматологии в 2021 г.[30].…”