Siltuximab is a chimeric human-mouse monoclonal antibody to interleukin-6 which is used in the therapy of Castleman disease. Siltuximab commonly causes mild serum aminotransferase elevations which are usually short lived and asymptomatic, but it has not been linked to instances of clinically apparent liver injury with jaundice.


Siltuximab (sil tux' i mab) is human-mouse chimeric IgG1 monoclonal antibody to IL-6 that is used largely as therapy of autoinflammatory diseases such as Castleman disease. Siltuximab binds to and blocks the action of IL-6, which is a key proinflammatory cytokine that mediates a wide spectrum of biologic activities including activation of T cells, differentiation of B cells, induction of acute phase reactants, proliferation of fibroblasts, and damage to cartilage and joints. IL-6 levels are elevated in patients with autoinflammatory conditions and in some forms of cancer. In controlled trials and open label studies, siltuximab therapy led to improvements in symptoms and laboratory abnormalities associated with Castleman disease. It has also been used in chemotherapy of prostate cancer and multiple myeloma, but with only limited effects. Siltuximab was approved for use in the United States in 2014 and current indications are limited to adults or children above the age of 12 with multicentric Castleman disease. Siltuximab is given by intravenous infusion every 3 weeks, in doses of 11 mg/kg. Siltuximab is available as lyophilized powder in single use vials of 100 and 400 mg under the brand name Sylvant. The most frequent side effects are itching, weight gain, rash, upper respiratory symptoms, headache, fatigue, diarrhea, infusion reactions and hyperuricemia. Rare, but potentially severe adverse reactions include worsening of severe infections, infusion reactions and gastrointestinal perforation.


In clinical trials of siltuximab combined with conventional chemotherapeutic agents in treatment of cancer, serum aminotransferase elevations occurred in a high proportion (10% to 30%) of patients. These trials included mention of some patients with elevations of ALT levels above 5 times the upper limit of normal and at least one example of reactivation of hepatitis B in a patient with multiple myeloma who also received dexamethasone. In studies of Castleman disease, however, rates of ALT elevations were usually not mentioned, although one instance of values above 5 times ULN were reported in one series. In these trials, no patient developed clinically apparent liver injury attributable to siltuximab. Since its licensure and general availability, there have been no published reports of hepatotoxicity due to siltuximab. Thus, siltuximab must be a rare cause of clinically apparent liver injury, if it occurs at all.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

Siltuximab is a monoclonal antibody and is metabolized by many tissues into smaller polypeptides and amino acids. The mechanism by which it might cause liver injury is unknown, but it could possibly cause liver injury as a result of its effects on the immune system or on the IL-6 pathway which is important in liver regeneration. Siltuximab may be capable of causing reactivation chronic hepatitis B.

Outcome and Management

The serum enzyme elevations that have occurred during siltuximab therapy have been without symptoms or jaundice and short lived, resolving within a few weeks even without dose adjustment or discontinuation. There is no reason to suspect cross sensitivity to hepatic injury between siltuximab and other monoclonal antibodies known to cause liver injury such as infliximab and adalimumab.

Drug Class: Monoclonal Antibodies; Immunosuppressive Agents



Siltuximab – Sylvant®


Immunosuppressive Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 09 April 2016

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    (Expert review of hepatotoxicity published in 1999 before the availability of siltuximab and other monoclonal antibodies and anticytokines).
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    (Among 281 patients with refractory multiple myeloma treated with siltuximab or placebo combined with bortezomib, addition of siltuximab was not associated with improved progression free survival, but was associated with increased rates of neutropenia and thrombocytopenia, and slight increases in ALT and AST were observed on day 1 of cycle 2 in both groups, “but mean values remained in the normal range throughout the randomized treatment phase”).
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    (Review of Castleman disease and its therapy including use of siltuximab; no mention of ALT elevations or hepatotoxicity).