Olokizumab significantly improves RA features and patient-reported outcomes

Results from the phase 3 CREDO-1 trial show that treatment with olokizumab over a 24-week period was associated with significant improvements in the signs, symptoms, and physical function of rheumatoid arthritis (RA) as well as in patient-reported outcomes (PROs) in patients with moderate-to-severe RA who previously failed methotrexate therapy [1,2].

Prof. Rumen Stoilov (University Hospital St. Ivan Rilski, Bulgaria) presented the randomised, placebo-controlled, multicentre, phase 3 CREDO-1 trial that evaluated the efficacy and safety of olokizumab, a new humanised monoclonal antibody targeting interleukin(IL)-6 [3,4]. The trial aimed to evaluate the safety and efficacy of olokizumab 64 mg administered subcutaneously every 2 weeks and 64 mg subcutaneously every 4 weeks versus placebo in the treatment of moderate-to-severe active RA despite treatment with methotrexate. Participants (n=428) received injections of olokizumab 64 mg every 2 weeks (n=143), olokizumab 64 mg every 4 weeks (n=142), or placebo every 2 weeks (n=143) for 24 weeks. After week 24, patients could qualify for an open-label study extension. Primary endpoint of the study was American College of Rheumatology (ACR)20 response at week 12. Secondary endpoints included percentage of patients with low disease activity and improvement of physical ability. Baseline characteristics were comparable between treatment arms.

The results showed that 90.9% of patients in the 2-week dosing group, 94.4% in the 4-week dosing group, and 92.3% in the placebo group completed the study. Both regimens of olokizumab were significantly better than placebo in all primary and secondary endpoints, with 63.6% of patients in the 2-week dosing group and 70.4% of those in the 4-week dosing group achieving ACR20 at week 12 versus 25.9% of patients receiving placebo. The rates for disease activity score (DAS)28 response were 33.6%, 38.7%, and 3.5%, respectively.

Regarding the effect of treatment on quality of life (QoL), work productivity, and fatigue, the 3 groups were compared for a wide range of PROs, including change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); Patient Global Assessment of Disease Activity (PtGA); Patient Assessment of Arthritis Pain (Pain); Short Form 36 (SF-36) Physical (PCS) and Mental (MCS) components; European Quality of Life-Five-Dimension Questionnaire (EQ-5D); Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F); and Work Productivity Survey-Rheumatoid Arthritis (WPS-RA) [2]. PRO baseline characteristics were comparable across treatment arms: mean (SD) PtGA was 69.5 (15.5); Pain was 68.6 (17.5); HAQ-DI was 1.7 (0.5); SF-36 PCS was 32.1 (6.5); SF-36 MCS was 42.3 (10.0); EQ-5D was 40.3 (20.0); and FACIT-F was 26.8 (8.7). At week 12, treatment with olokizumab 64 mg every 2 weeks and olokizumab 64 mg every 4 weeks resulted in significant improvement in PRO measures, and these improvements were persistent up to week 24 (see Table).

Table: Patient-reported outcomes change from baseline [2]

* Secondary endpoint; ** P<0.0001.EQ-5D, European Quality of Life-Five-Dimension Questionnaire; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue Scale; HAQ-DI, Health Assessment Questionnaire-Disability Index; LSM, least square mean; MCS, mental components; PCS, physical components; PtGA, Patient Global Assessment of Disease Activity; SE, standard error; SF-36, Short Form 36; q2w, every 2 weeks; q4w, every 4 weeks.

The incidence of treatment-emergent serious adverse events was numerically higher in the olokizumab groups when compared to placebo, but no unexpected safety signals emerged [1]. The safety profile of olokizumab was consistent with what had previously been shown in phase 2 trials with this agent and with data for agents with a similar mechanism of action. At a time when interleukin-6 blockers are in short supply this work highlights the ongoing interest of interleukin-6 antagonism in rheumatoid arthritis.

1. Nasonov E, et al. Abstract OP0021. EULAR E-Congress, 3-6 June 2020.


2. Nasonov E, et al. THU0176. EULAR E-Congress, 3-6 June 2020.


3. Genovese MC, et al. Ann Rheum Dis. 2014;73:1607-1615.


4. Takeuchi T, et al. Mod Rheumatol. 2016;26:473-480.

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Posted on 14 August, 20205 August, 2021