Chloroquine may be non-inferior to methotrexate in achieving complete clinical response in the treatment of patients with cutaneous disease in systemic lupus erythematosus (SLE), according to results recently published in JAMA Dermatology. 

“Systemic lupus erythematosus is an autoimmune disease that affects multiple organ systems and has substantial morbidity and mortality. Cutaneous disease in SLE is common and can have a profoundly negative outcome on quality of life,” Mohsen Afarideh, MD, MPH, from the Corporal Michael J. Crescenz Veterans Affairs Medical Center, Department of Dermatology at the University of Pennsylvania, and Perelman School of Medicine, and colleagues wrote in the study. “This synopsis summarizes findings from a Cochrane review of interventions for cutaneous disease in SLE."

To determine the efficacy of interventions for cutaneous disease in patients with SLE in randomized clinical studies, the researchers compared interventions for cutaneous disease in SLE vs placebo, secondary treatment, or different doses of the same intervention. 

 A total of 61 randomized clinical trials made up of 11,232 patients aged 18 to 80 years from outpatient clinics and academic and research institutions from 50 countries were included in the Cochrane Review.  

The primary outcomes of the study were complete clinical response defined as complete disease resolution, and partial clinical response. 

Secondary outcomes included clinical flares, time to flare, relapse rate when medications are stopped or reduced, skin-specific measures of SLE disease activity, dermatology quality-of-life measures, and adverse events. 

Interventions with significant achievement of complete clinical response compared with placebo include methotrexate, dehydroepiandrosterone, and baricitinib, according to the data. For baricitinib, the end point was resolution of arthritis or rash combined; the researchers saw no evidence for specific efficacy in skin.

The interventions that researchers found to be noninferior in head-to-head comparisons in achieving complete clinical response include methotrexate vs chloroquine, ciclosporin vs azathioprine, clofazimine vs chloroquine, ciclosporin A plus intravenous and oral steroids vs oral steroids alone, and topical tacrolimus vs topical clobetasol. 

There was a significant difference between topical tacrolimus and topical clobetasol in achieving complete clinical response of telangiectasias, but this was more likely a difference in adverse effect profiles, according to the results of Cochrane review.

It was also found that interventions with clofazimine vs chloroquine and mycophenolate vs azathioprine or dapsone were noninferior in head-to-head comparisons in achieving partial clinical response.

Hydroxychloroquine was the only intervention found to have a significantly different rate of clinical flares compared with placebo, according to the data presented.

Secondary outcomes were achieved using Cutaneous Lupus Disease Area and Severity Index as defined in each study compared with placebo when using intravenous sifalimumab, repository corticotropin injection, intravenous anifrolumab, and intravenous ustekinumab.

According to the study, intravenous belimumab achieved secondary outcomes using the mucocutaneous domains of the British Isles Lupus Assessment Group index and the Systemic Lupus Erythematosus Disease Activity Index at a significant rate compared with placebo; however, it was unclear how response varied across cutaneous lupus subtypes. 

While the response of cutaneous disease in patients with SLE in the randomized controlled trials  reviewed generally aligned with what is expected in patients with isolated cutaneous lupus, the researchers suggest a need for further studies. 

"Skin-focused and overall results from the trial of recently approved anifrolumab are promising. Similarly, biologics such as BIIB059 and iberdomide have met their primary end points of reducing Cutaneous Lupus Disease Area and Severity Index in phase 2 trials of both SLE and cutaneous lupus erythematosus," the researchers wrote. "However, skin-specific effects of small-molecule inhibitors such as baricitinib need further investigation."