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

Abstract

ObjectivesTo assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IRs).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, the patients were randomised in a 2:2:1 ratio to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or PBO plus methotrexate. At week 16, the patients on PBO were randomised to receive either OKZ regime. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. Disease Activity Score 28-joint count C-reactive protein (DAS28 (CRP))<3.2 at week 12 was the major secondary efficacy endpoint. Safety and immunogenicity were assessed.ResultsIn 368 patients randomised, ACR20 response rates were 60.9% in OKZ q2w, 59.6% in OKZ q4w and 40.6% in PBO (p<0.01 for both comparisons). Achievement of DAS28 (CRP) <3.2 was significantly different, favouring the OKZ arms. Improvements in efficacy and patient-reported outcomes were maintained throughout 24 weeks and were noted after week 16 in patients who switched from PBO.Dose-related treatment-emergent serious adverse events were 7% in OKZ q2w, 3.2% in OKZ q4w and none in the PBO group.ConclusionsDirect inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNF-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor.Trial registration numberNCT02760433.

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

“…In total eight trials investigating bDMARDs with or without concomitant csDMARD were included (six with low RoB, one with high RoB, one conference abstract). Primary results are summarised in table 2 13–21…”

“…Trials on OKZ (anti-IL6 cytokine) and LEV (anti-IL6 receptor) confirmed the efficacy of inhibiting the IL6-pathway in RA. Both molecules showed superior efficacy compared with placebo 15–17 19. Further, olokizumab treatment was non-inferior to ADA (both in combination with MTX) in MTX-IR patients 29 30…”

Management of patients with rheumatoid arthritis in real clinical practice: Switching from interleukin 6 receptor inhibitors to interleukin 6 inhibitor (olokizumab)

“…В связи с этим значительный интерес представляет первый российский иИЛ-6 препарат олокизумаб (ОКЗ) − гуманизированное моноклональное антитело (IgG4κ), специфически нейтрализующее ИЛ-6 [13]. Он применяется вместе с МТ для лечения РА у пациентов, не достигших ремиссии или низкой активности при использовании БПВП или ингибиторов ФНО-α (иФНО-α) [14,15]. ОКЗ относится к классу иИЛ-6, но по механизму действия отличается от тоцилизумаба (ТЦЗ) и сарилумаба (САР), которые блокируют рецептор ИЛ-6 (ИЛ-6Р).…”

“…Свою эффективность и безопасность у пациентов с РА ОКЗ показал в рамках международной программы фазы III CREDO [14,15,18]. Так, он оказался эффективным у 60% больных РА, имевших недостаточный ответ на терапию иФНО-α [15]. Эффективность комбинированной терапии ОКЗ и МТ в сравнении с плацебо подтверждена и метаанализом [19].…”

Efficacy of olokizumab against comorbid depressive disorder in patients with rheumatoid arthritis: Preliminary results of the study

“…С мая 2020 г. в России для лечения взрос лых пациентов с РА средней и высокой степени активности с успехом используется олокизумаб (ОКЗ) -гуманизированное моноклональное антитело (IgG4κ), специфически нейтрализующее ИЛ-6, фармакокинетические характеристики, эффективность и безопасность которого при РА были доказаны в трех РКИ (CREDO-1, -2 и -3) [12][13][14].…”