The effect of olokizumab on rheumatoid arthritis patient’s reported outcomes: results of a double-blind randomized placebo-controlled multicenter phase III trial (CREDO 1)

Abstract

Background. Olokizumab is a new interleukin-6 (IL-6) inhibitor that has demonstrated good efficacy and safety for the treatment of adult patients with moderate to high-grade activity of rheumatoid arthritis in combination with methotrexate with insufficient efficacy of methotrexate monotherapy.Aim of the study was to evaluate the effectiveness of olokizumab in relation to the patient’s reported outcomes (PROs) based on the results obtained in the CREDO 1 phase III study.Material and methods. The study included 428 patients with rheumatoid arthritis who were randomized into 3 groups: group 1 – patients who received 64 mg of olokizumab subcutaneously every 2 weeks (q2w) (n=143); group 2 –patients who received 64 mg of olokizumab every 4 weeks (q4w) (n=142); group 3 – patients who had placebo q2w (n=143). PROs included: Health Assessment Questionnaire-Disability Index (HAQ-DI); Patient Global Assessment of Disease Activity (PtGA-VAS); Subject’s Assessment of Pain (VAS); fatigue according to the FACIT-F scale; quality of life according to the EQ-5D questionnaire; physical and mental components of the SF-36 scale. The effectiveness of olokizumab was evaluated by the dynamics of the average PROs values and the proportion of patients who reported improvement compared to the baseline level of ≥ minimum clinically important differences (MCID) for each PROs by weeks 12 and 24 of follow-up.Results. 396 patients out of 428 included completed the study. When included in the study, patients of different therapeutic groups did not differ in socio-demographic indicators, duration, activity of rheumatoid arthritis, as well as in PROs indicators. Olokizumab therapy, regardless of the dosage regimen of the drug, resulted in a significant improvement in all PROs compared to placebo after 12 weeks, and this improvement sustained until 24 weeks of therapy. The proportion of patients who reached and exceeded MCID at weeks 12 and 24 of follow-up was statistically significantly higher in both olokizumab groups compared to placebo for PtGA, VAS pain, HAQ-DI, FACIT-F. The number of patients who reached or exceeded the MCID on the physical component of the SF-36 scale at week 12 was significantly higher in both olokizumab groups, and at week 24 only in the group 2 compared to the placebo group. The mental component of SF-36 improved in a significantly higher percentage of patients in the group 2 compared to placebo group at weeks 12 and 24, while the group 1 did not significantly differ from placebo group in improving the mental component of SF-36.Conclusions. Olokizumab therapy in patients with moderate to high-grade activity of rheumatoid arthritis is associated with a significant improvement in all PROs. There was no significant difference between the dosage regimens of olokizumab.

Keywords

• rheumatoid arthritis
• il-6 inhibitors
• olokizumab
• credo 1
• patient’s reported outcomes