A new drug safety signal “Dimethyl fumarate included Alopecia areata” identified by Netherlands Pharmacovigilance center, Lareb
Dimethyl fumarate is an anti-inflammatory and immunomodulatory agent which is used in the treatment of relapsing multiple sclerosis and plaque psoriasis.
Alopecia areata is an autoimmune disorder which involves loss of hair follicle with one or more circular bald patches which might overlap causing spot baldness.
Lareb received 92 case reports pertaining to dimethyl fumarate and alopecia areata drug-event combination from the Netherlands Pharmacovigilance database during the period 02-Nov-2006 to 11-Jun-2020 with a significant spike in cases from the year 2018. Lareb identified this association as disproportionate in the national drug safety database, EudraVigilance and WHO databases (VigiBase).
Source: 71 cases from marketing authorization holders; 21 directly reported spontaneous cases to Lareb
Suspected Product name (Brand): Tecfidera®- 82 cases, Psorinovo® – 2 cases and not reported for remaining cases.
Therapeutic Indication: Multiple sclerosis- 84 cases, Psoriasis- 6 and not reported for two cases.
Patient’s Gender: 81 Female & 11 Male
Age group: 19 to 74 years (median age: 40 years)
Temporal relationship: TTO (time to onset) for the hair loss symptom varied from several weeks up to months after treatment initiation. (Average TTO: 61 days)
Temporal relationship is in line with Dimethyl fumarate’s mechanism of action (activation of nuclear factor erythroid-derived 2-like (Nrf2) –> dilatation of hair follicles and hair loss during the catagen and telogen phase)
Dechallenge: Positive in 13 cases (recovery from hair loss after drug withdrawal)
Rechallenge: Positive in 1 case (re-occurrence of hair loss due to re-introduction of drug)
Safety evidence from Literature: A case report published in the year 2016 pertaining to a 55-year old woman described transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis.
Un-labelled safety finding: Lareb stated that alopecia areata is not described in the labelling document-Dutch Summary of product characteristics of all the dimethyl fumarate containing medicinal products.
Possible mechanism for ADR:
Dimethyl fumarate acts by up-regulating/activating the Nrf2 pathway by glutathione depletion which is attributed for its therapeutic benefits. The same mechanism has potential contribution for hair loss which involves dilatation of the hair follicle during the transitional (catagen) and resting phase of the hair. Dimethyl fumarate may also cause alopecia by a direct cytotoxic effect which could be caused by conjugation of dimethyl fumarate with glutathione which can lead to intracellular glutathione depletion
Based on the current safety evidence from 92 case reports and medical literature, Lareb alerts health care professionals to be aware of alopecia areata as a potential adverse drug reaction for dimethyl fumarate.