The impact of comorbidities on the efficacy of IL-6 inhibitor olokizumab compared to adalimumab in a randomized controlled trial

Patients with rheumatoid arthritis (RA) have an increased prevalence of comorbidities, which is associated with higher RA disease activity and worse disease outcomes. The aim of this analysis was to evaluate the impact of the comorbidity burden on the efficacy of the IL-6 inhibitor olokizumab (OKZ) and the tumour necrosis factor (TNF) inhibitor adalimumab (ADA) in the CREDO-2 randomized controlled clinical trial cohort of patients with active RA. A total of 1402 patients with RA were included in the analysis and divided into two groups on the basis of the modified Charlson Comorbidity Index (mCCI) at baseline: those having no comorbid conditions, NCC (mCCI = 1; RA only) vs. those having comorbid conditions, CC (mCCI ≥ 2; RA and ≥ 1 comorbidity). The key outcomes at Week (W) 24 were the proportions of patients with CDAI ≤ 10 and CDAI ≤ 2.8, other outcomes were ACR50 (W12, W24), proportions of patients with SDAI ≤ 3.3 (W24). All groups had similar proportions of approximately 25% of patients with mCCI ≥ 2. There was no significant difference in efficacy between the OKZ q4w or q2w-treated NCC and CC groups at 3 and 6 months of treatment. The same was observed for the placebo group. In contrast, comorbidities reduced CDAI ≤ 10 and ACR50 outcomes upon ADA treatment at 6 months. This post hoc analysis of the phase III CREDO-2 study suggests that the presence of at least one CCI comorbidity, including common disorders such as chronic pulmonary diseases and cardiovascular diseases, does not affect the OKZ treatment results in RA patients. In contrast, comorbidities reduce several efficacy outcomes upon ADA treatment at 6 months. The CCI was not associated with placebo group results and had no influence on safety outcomes. NCT02760407 submitted 2016-05-02.