Predictive factors for induction of remission in patients with active rheumatoid arthritis treated with tocilizumab in clinical practice
Introduction
Treatment goals for rheumatoid arthritis (RA) have shifted toward achieving remission [1]. Many biological therapies for RA have become available during the past decade (including TNF blockers, abatacept, rituximab, or tocilizumab), making clinical remission an achievable goal. However, responsiveness to biological agents is variable among individuals, and there are poor responders to certain biologic treatments. Given the destructive nature of RA, the risk of adverse events, and the considerable costs of biologic therapy, there is a need to identify predictors of response to biologics, which should allow for more personalized therapy.
Tocilizumab (TCZ) is a humanized interleukin-6 (IL-6) receptor monoclonal antibody that competitively inhibits the binding of IL-6 to its receptor [2]. It was approved in Europe in 2009 for the treatment of moderate to severe RA in patients with inadequate response to one or more disease modifying anti-rheumatic drugs (DMARDs) and/or TNF antagonists [3]. However, although it has been on the market for a long time, information about the predictive factors of early response to TCZ, which would be of use in routine clinical practice, remains limited. For this reason, this study aimed to identify the predictive factors for induction of remission in a real-life cohort of 126 patients with active RA treated with TCZ as the first biological therapy or after failure of at least one biological agent.
Section snippets
Methods
The sample included all patients with active RA (all of whom met the American College of Rheumatology (ACR) classification criteria for RA) [4] who were routinely treated from January 2009 to November 2012 with TCZ at the rheumatology departments of four referral tertiary care hospitals from Barcelona (Spain) and followed for at least 6 months after beginning TCZ treatment. A retrospective analysis of prospectively collected data was performed.
In accordance with the guidelines of our
Baseline characteristics
Patient and treatment characteristics at baseline are shown in Table 1. All patients had a history of failed treatment with at least one DMARD (mean ± SD: 2.53 ±1.4; range: 1–7). Of the 126 patients, 43 (34%) received TCZ monotherapy and 83 (66%) received TCZ plus DMARD, 55 received methotrexate (MTX), 26 leflunomide (LEF), and 2 sulfasalazine (SSZ). The average dose of MTX was 16.1 ± 6.0 mg/week (median 15.0 mg/week; range: 7.5–25). For oral LEF, 21 patients received 20 mg/day, and 5 received 10
Discussion
The current treatment goal of RA is remission [1]. New biologic treatments have become available over the past decade, making remission an achievable goal. However, responsiveness to biological agents is variable, and some patients respond poorly to certain treatments. Therefore, the broad therapeutic arsenal currently available makes identifying the predictors of early clinical response to biologics a salient and current issue in the management of RA.
There is only limited evidence available
Ethics approval
In accordance with the guidelines of our institutional ethics committee [Comité Ético de investigación Clínica (CEIC) del Hospital Universitario de Bellvitge] formal approval for this study was not required. The local ethics committee agreed that the findings in this report were based on normal clinical practice and therefore were suitable for dissemination. Patient’s informed consent was not obtained, but their clinical records/information was anonymized and de-identified prior to analysis.
The
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2021, Autoimmunity ReviewsCitation Excerpt :We identified 8 research articles that specifically evaluated if inflammatory markers could predict a response to tocilizumab (TCZ) [13,15–21] and none for other IL-6 inhibitors. Five were observational studies [13,15,19–21] and 3 post-hoc analysis of randomised controlled trials (RCTs) [16–18]. None of the post-hoc RCTs analyses found an association between baseline levels of inflammatory markers and response.
The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab
2018, Seminars in Arthritis and RheumatismPrediction of Response to Targeted Treatment in Rheumatoid Arthritis
2017, Mayo Clinic ProceedingsCitation Excerpt :In a multicenter observational study of 126 patients with RA who failed previous bDMARD therapy, the predictors of achieving DAS28-erythrocyte sedimentation rate (ESR) remission at 3 months were baseline ESR greater than 30 mm/h, CRP level greater than 10 mg/L, and the presence of extra-articular disease manifestations. In contrast, a lower likelihood of achieving DAS28 remission was associated with higher baseline hemoglobin concentrations, higher baseline DAS28-ESR, and the number of previous DMARDs and biological therapies used.42 Several studies reported no relationship between RF or ACPA positivity and the clinical response to tocilizumab treatment.42,43,82
J.N. oversaw the analysis, conceptualized the project, and drafted the article. J.N., B.M., C.D.T., M.V.H., D.R., and H.C. provided the data and revised the article. R.S., J.M.L.L., A.R.S., and J.M.N. revised the article.