Tocilizumab suitable alternative to TNF inhibitors in DMARD-naïve patients with RA
Tocilizumab, in monotherapy or in combination with conventional synthetic DMARDs, is an adequate alternative to combination therapy with a TNF inhibitor in patients with rheumatoid arthritis who have not yet been treated with either biological or targeted synthetic DMARDs, according to recent findings in Seminars in Arthritis and Rheumatism.
“We know that the population prescribed tocilizumab is very different from the population in trials,” Kim Lauper, MD, of Geneva University Hospitals in Switzerland, told Healio Rheumatology. “Although there were studies in bio-naïve patients evaluating efficacy of tocilizumab as monotherapy, to our knowledge, no real-world study compared the effectiveness of tocilizumab and TNF-inhibitors with or without [conventional synthetic] DMARDs in bio-naïve patients before.”
“Secondly, in a previous study with bio-experienced patients, we found that the drug retention, which is a measure of effectiveness and safety, was higher with tocilizumab — as monotherapy or in combination with csDMARDs — than TNF-inhibitors in combination with csDMARDs,” she added. “However, one of the possible explanations we had was that this could be linked to the fact that patients with tocilizumab usually failed more [biologic] DMARDs than patients with TNF-inhibitors and did not have many options left. So, we wanted to evaluate this in bio-naïve patients.”
To compare the effectiveness of tocilizumab (Actemra, Genentech) with that of TNF inhibitors — either alone or in combination with conventional synthetic DMARDs — among patients with RA without previous biological DMARD treatments, Lauper and colleagues studied data from the Tocilizumab Collaboration of European Registries in RA (TOCERRA), a collaboration of several national, longitudinal databases. Specifically, the researchers analyzed seven registries that included patients with RA and no previous history of DMARD treatment who received either tocilizumab or a TNF inhibitor.
Eligible patients first received treatment with either tocilizumab or a TNF inhibitor between Jan. 1, 2009, and March 15, 2018. The study included 6,713 patients treated with TNF inhibitors as part of combination therapy, 3,762 who received TNF inhibitors alone, 646 treated with tocilizumab in combination therapy and 384 who received tocilizumab monotherapy.
The researchers assessed drug retention using Kaplan–Meier and Cox models. Clinical Disease Activity Index (CDAI) was analyzed over time using mixed models. Low disease activity rates and remission after 1 year were corrected for attrition.
According to Lauper and colleagues, after adjustment for covariates, such as country and year of treatment initiation, the risk for discontinuation was lower among patients in both the tocilizumab monotherapy (HR = 0.6; 95% CI, 0.52-0.69) and tocilizumab combination (HR = 0.66; 95% CI 0.540.81) groups, compared with those in the TNF inhibitor combination group. Adjusted CDAI changes were not significantly different between groups. Low disease activity and remission, corrected for attrition, were also similar between those treated with tocilizumab with or without conventional synthetic DMARDs and TNF inhibitors with combination therapy.
“We found that drug retention was higher with tocilizumab as monotherapy and in combination with csDMARDs than TNF-inhibitors in combination with csDMARDs,” Lauper said. “We also found that CDAI evolution over time and CDAI low disease activity and remission at one year were similar between groups. As expected, TNF-inhibitors as monotherapy had the lowest drug retention rate. For patients who do not tolerate csDMARDs or who have contraindications to csDMARDs, tocilizumab seems to be a more suitable alternative than TNF-inhibitors when a step-up therapy is needed.” – by Jason Laday
Disclosure: Lauper reports an unrestricted research grant from AbbVie, as well as non-financial support from Pfizer. Please see the full study for additional authors’ disclosures.