New Lupus Drug Cuts Skin Disease When Other Agents Fail

Every patient with discoid lupus erythematosus (DLE) that had not responded to multiple standard medications showed substantial improvement when put on anifrolumab (Saphnelo) in a small retrospective study, researchers said.

Among eight patients treated with anifrolumab for at least 8 weeks, mean scores on the Cutaneous Lupus Erythematosus Disease Area and Severity Index's (CLASI) activity subscale declined 65%, according to Katharina Shaw, MD, of Brigham and Women's Hospital in Boston, and colleagues.

All patients registered some decline in CLASI activity scores, ranging from 46% to 79%, the researchers reported in JAMA Dermatology. Both pruritus and pain were rated by patients as "significantly improved" in all cases, and no adverse events were recorded.

DLE is a form of chronic cutaneous lupus that "is distinguished by its potential to cause irreversible scarring and disfigurement," Shaw and colleagues explained. Drugs used for systemic lupus are the principal therapies for DLE, but these "demonstrate inconsistent success," the researchers added.

Shaw and colleagues said they were intrigued by a finding in one of the pivotal trials underpinning anifrolumab's 2021 approval for systemic lupus: 49% of patients taking the drug showed at least 50% reduction in skin manifestations, compared with 25% of the placebo group.

Anifrolumab has a unique mechanism of action: a monoclonal antibody, it targets the type 1 interferon receptor subunit 1. Because "type 1 interferon expression is known to correlate with DLE disease activity," Shaw and colleagues wrote, "we hypothesized that anifrolumab might be a viable therapeutic option for patients with DLE."

They searched records at Brigham and Women's and its sister institution, Massachusetts General Hospital, for patients with DLE treated with anifrolumab. Ten such patients were found, but two had not received the drug for at least 8 weeks and were excluded.

The remaining eight were all women, with a mean age of 43. All had previously received hydroxychloroquine (HCQ) and at least one other drug without bringing their skin manifestations under control. Besides HCQ, most had taken methotrexate, prednisone, and mycophenolate mofetil. (One patient had tried 11 other agents.) CLASI activity scores at baseline ranged from 11 to 39.

Shaw and colleagues included a set of before-and-after photographs of one "representative" patient, a Black woman in her 40s. Prior to starting anifrolumab, the woman had complete alopecia on the scalp and crusty lesions on her head, arms, and chest. With the drug on board for 2 months, the scaling had largely abated. The researchers said that by month 6, her daily prednisone dose was tapered from 10 mg to 2 mg.

Areas of hyper- and hypo-pigmentation remained, however, and no hair regrowth was visible. Shaw and colleagues said this was to be expected in cases of uncontrolled DLE for long periods, and some of the effects such as scarring are permanent. Indeed, no patient in the study saw reductions of more than 2 points on the 56-point CLASI damage subscale.

"Taken together, these early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease," the investigators concluded. They called for larger prospective studies to confirm the benefit.

Correction: A previous version of this article referred to anifrolumab as an IL-1 blocker, the drug is a type 1 interferon receptor antagonist.

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