Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions

Abstract

BackgroundSince approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion.MethodsPreparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement.ResultsThe consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise.ConclusionsThe consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition.

Targeting Interleukin-6 in Rheumatoid Arthritis

“…Anaphylactic reaction was more common in the toclizumab 4mg/kg group than the 8mg/kg group [28]. Antibodies to tocilizumab occurred in about 2-4% of the patients although this did not seem to predispose the hypersensitivity reactions [28].…”

“…A recent Consensus indicated that tocilizumab may be used in adult patients with active RA, normally with at least moderate disease activity according to a validated composite measure, who have had an inadequate response to, or intolerance of at least one synthetic DMARD and/or a TNF-inhibitor [28]. In 2012, both the National Institute for Health and Clinical Excellence (NICE) of the United Kingdom and the Food and Drug Administration (FDA) agency of the United States have expanded the approved indication of tocilizumab to be used as a "first-line biological agent" in RA patients who have had an inadequate response to one or more synthetic DMARDs.…”

“…The infusion was maintained and the event subsequently resolved without further complication. Temporary thrombocytopenia resulted from the decrease in IL-6 after starting tocilizumab as thrombocytosis is mediated by IL-6 [28].…”

“…It is still uncertain whether this is also the case with tocilizumab treatment. Until data are widely available, caution needs to be taken in prescribing tocilizumab particularly in patients with pre-existing disease and in patients with a positive family history of demyelinating disease [28].…”

Rheumatoid arthritis: Biological therapy other than anti-TNF

“…TCZ, either as monotherapy or in combination with MTX, was significantly more efficacious than MTX alone [32] and it is possibly superior to adalimumab in monotherapy. The FDArecommended dose is 4 mg/kg administered via the IV route every 4 weeks, and 162 mg administered via the subcutaneous route every other week, followed by an increase to 8 mg/kg (i.v., q4w) or 162 mg (s.c., qw) based on clinical response [33] and [34]. SC formulations of biologic DMARD have been developed in order to facilitate their use outside hospitals by permitting self-administration.…”