This is the third drug safety signal – “Cutaneous Vasculitis association with Tocilizumab use” detected from the VigiBase by the UMC (Uppsala Monitoring Center). UMC is a WHO Collaborating Centre present in Sweden for international service and scientific research within the field of pharmacovigilance.
Tocilizumab is an immunosuppressive agent and a biologic medication (fully human monoclonal antibody) used in the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis. It acts by inhibiting the inflammatory cytokine, interleukin-6 (IL-6) thereby reducing the abnormal IL-6 levels. IL-6 is involved in the immunological and inflammatory reactions. Cutaneous Vasculitis involves the inflammation of peripheral small and medium sized blood vessels (arteries and veins) confined to skin which can affect any part of the body.
UMC identified 16 case reports from VigiBase for the drug event combination- Tocilizumab -Cutaneous Vasculitis during their routing signal detection analysis. These cases were reported during the period of June 2012 and April 2019 from nine countries.
Case-Stratification:
Therapeutic indication: 15 cases were reported with RA as indication and other case reported juvenile idiopathic arthritis.
Age: 16 to 78 years; (median age: 63, from 13 case reports)
Gender: 11 Males & 5 Females
Seriousness: 13 cases classified as serious (life-threatening, prolonged hospitalization and disability are reported criteria)
Analysis of case reports supporting causal relationship for ‘Tocilizumab -Cutaneous Vasculitis’ pair
Temporal relationship: 2 to 540 days with a median of 60 days for the onset of reaction (Time to onset is recorded only in 6 case reports)
Dechallenge: Positive in 6 case reports, unknown in 3 cases and not reported in 7 cases.
Rechallenge: Positive in 1 case report and not reported for remaining cases.
Alternative explanations: Concurrent medication use which included TNF-alpha inhibitors (etanercept, adalimumab), methotrexate, folic acid rituximab etc.,
Cutaneous vasculitis is not a labelled adverse drug reaction in the United states Prescribing information (USPI) document.
Based on the available evidence from the 16 case reports, which included 6 positive dechallenge and one positive rechallenge outcomes, UMC concluded a causal link between tocilizumab and cutaneous vasculitis.