Updated Consensus Statement for IL-6 Pathway Inhibition in Inflammatory Diseases

The current literature indicates that use of interleukin-6 (IL-6) receptor blocking provides a major therapeutic advancement for individuals with various inflammatory conditions, according to findings published in Annals of the Rheumatic Diseases.

A task force of multidisciplinary experts and patient representatives updated the existing consensus statement regarding the use of IL-6 inhibition for inflammatory conditions. They conducted a systematic literature review to analyze the most recent evidence on specific indications for use, effective dosing of IL-6 pathway inhibitors, safety, and patient management aspects.

Indications for Use

The highest levels of evidence, ranging from level 1a to 2c and grades A or B, indicated effective use of IL-6 pathway blockers in rheumatoid arthritis (RA), polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still disease, Castleman disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder, and severe COVID-19.

Dosing

The researchers identified the following IL-6 pathway blocking agents: tocilizumab, sarilumab, satralizumab, siltuximab, sirukumab, clazakizumab, olokizumab, EBI-028, olamkicept, and Janus kinase 1,3-inhibitors. Dosing should be determined by indication.

Based on findings from previous studies, optimal dosages for treatment are:
• Sarilumab, subcutaneously: 200 mg administered every 2 weeks
• Tocilizumab, subcutaneously: 162 mg every week
• Tocilizumab, intravenously: 8 mg/kg over 1 hour every 4 weeks

Safety

Primary safety issues, particularly in patients treated with tocilizumab, included the possibility of severe infections, neutropenia, increased hematocrit and hemoglobin levels, gastrointestinal perforations, adverse hepatic events (such as elevated transaminase levels), elevated lipid levels, and induction of macrophage activation syndrome (MAS) in children. Hypersensitivity reactions occurred with a low frequency in the subcutaneous or intravenous administration of tocilizumab and the subcutaneous administration of sarilumab. Pregnant women had increased likelihood of preterm birth, spontaneous abortion, or elective termination.

With the exception of non-melanoma skin cancer, the researchers did not find any increased risk of developing malignancies from taking tocilizumab compared with other DMARDs. Tocilizumab was also not associated with increased risk of cardiovascular events compared with other DMARDs. Inhibition of IL-6 pathways did not exacerbate diabetes.

Major contraindications for use included known allergies to IL-6 inhibitors, as well as a vaccination history review. Live vaccines should not be administered during tocilizumab treatment.

Management

Prescreening includes medical history review and physical examination, evaluation of possible contraindications or precautions with use of IL-6 inhibitors, as well as a vaccination history review. Live vaccines should not be administered during tocilizumab treatment.

If the right indications are present, clinicians should monitor patients receiving IL-6 inhibition treatment, assessing IL-6 and C-reactive protein levels as a good predictor and measure of patient response to tocilizumab and sarilumab. Measurements of disease activity also suggest patient responsiveness to treatment and should be repeated every 3 months for patients with RA.

Lastly, concurrent use of glucocorticoids with IL-6 inhibitors is discouraged secondary to increased risk for significant cardiovascular adverse events and infections; however, disease flare-ups after withdrawal of glucocorticoids is possible.

“This article summarized the current state of these agents in terms of efficacy and safety, and the data regarding these areas have significantly advanced since the time of the first version of this consensus statement,” the study authors conclude. “Future research will provide even more insights and allow further expansion of these drugs’ profile for the benefit of patients with a large spectrum of inflammatory diseases.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Aletaha D, Kerschbaumer A, Kastrati K, et al. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update. Ann Rheum Dis. Published online August 11, 2022. doi:10.1136/ard-2022-222784