Systematic Review: Monoclonal Antibody-Induced Subacute Cutaneous Lupus Erythematosus

Abstract

Background Subacute cutaneous lupus erythematosus (S(CLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease. Methods We devised a set of diagnostic criteria for SCLE in collaboration with a multinational, multispecialty panel. This systematic review employed a two-layered search strategy of five databases for cases of mAb-induced SCLE (PROSPERO registered protocol CRD42019116521). To explore the relationship between relative mAb use and the number of SCLE cases reported, the estimated number of mAb users was modelled from 2013 to 2018 global commercial data and estimated annual therapy costs. Results From 40 papers, we identified 52 cases of mAb-induced SCLE, occurring in a cohort that was 73% female and with a median age of 61 years. Fifty percent of cases were induced by anti-tumour necrosis factor (TNF)-ɑ agents. A median of three drug doses preceded SCLE onset and the lesions lasted a median of 7 weeks after drug cessation. Oral and topical corticosteroids were most frequently used. Of the licensed mAbs, adalimumab, denosumab, rituximab, etanercept and infliximab were calculated to have the highest relative number of yearly users based on global sales data. Comparing the number of mAb-induced SCLE cases with estimated yearly users, the checkpoint inhibitors pembrolizumab and nivolumab showed strikingly high rates of SCLE relative to their global use, but ipilimumab did not. Conclusion We present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNFɑ agents.

Drug-induced subacute cutaneous lupus erythematosus in previously diagnosed systemic lupus erythematosus patients: A case series

“…5 Antietumor necrosis factor agents, in particular, etanercept, infliximab, adalimumab, and golimumab have also been associated with high rates of DI-SCLE. 6 Other medications with a strong DI-SCLE association include, but are not limited to, terbinafine, simvastatin, interferon alfa and beta, leflunomide, and carbamazepine. 5 The timeline of DI-SCLE can range from weeks to many months after initiation of the triggering medication, making identification of the offending medication and diagnosis difficult.…”

Subacute Cutaneous Lupus Erythematosus Associated with Ramucirumab Therapy

“…2 Hydralazine, procainamide, isoniazid are the three highest risk medications for lupus erythematosus, while SCLE associated medications are primarily hydrochlorothiazide, calcium channel blockers, and ACE inhibitors. 3 There has been increasing discussion surrounding chemotherapeutic agents inducing SCLE, with highest risk medications of docetaxel, paclitaxel, fluorouracil, capecitabine, tamoxifen citrate, and doxorubicin. 3 Ramucirumab is a fully human monoclonal antibody that targets VEGFR2, indicated in patients with hepatocellular carcinoma with prior treatment of sorafenib.…”

“…3 There has been increasing discussion surrounding chemotherapeutic agents inducing SCLE, with highest risk medications of docetaxel, paclitaxel, fluorouracil, capecitabine, tamoxifen citrate, and doxorubicin. 3 Ramucirumab is a fully human monoclonal antibody that targets VEGFR2, indicated in patients with hepatocellular carcinoma with prior treatment of sorafenib. Common side effects include thrombocytopenia, hypoalbuminemia, hyponatremia, neutropenia, fatigue, edema, and hypertension.…”

Cutaneous Manifestations in Biological-Treated Inflammatory Bowel Disease Patients: A Narrative Review

“…Compared to other drugs that induce lupus more anti-dsDNA antibodies, more hypocomplementemia, and less anti-histone antibodies are found. Lupus develops after a median of three drug doses and resolves after (a median of) 7 weeks stop of the biologic [ 56 ].…”

“…Anti-TNF-α induced lupus usually disappears after stopping the offending drug. Topical or systemic corticoids are most frequently used [ 56 ]. Antimalarials can be considered in case symptoms and remain present after cessation of the eliciting biologic.…”