Double‐blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus

Abstract

Objective. To evaluate the efficacy of clofazimine (CFZ) compared with chloroquine diphosphate (CDP) for the treatment of cutaneous involvement in systemic lupus erythematosus (SLE).Methods. A prospective, randomized, controlled, double-blind clinical trial was carried out in SLE patients with active cutaneous lesions, of whom 16 were randomized to receive CFZ at 100 mg/day and 17 received CDP at 250 mg/day for 6 months. All drugs had a similar appearance to avoid identification. Both groups received broad-spectrum sunscreens twice a day and the prednisone dose was kept stable during the study. Cutaneous lesions were evaluated by 2 blinded observers at baseline and at months 1, 2, 4, and 6.Results. Thirty-three patients were randomized to a treatment group, of whom 27 completed 6 months of treatment. The groups were homogeneous and comparable in terms of demographic and clinical characteristics. Five CFZ-treated patients and 1 CDP-treated patient (P ‫؍‬ 0.15) dropped out due to development of severe lupus flare. At the end of the study, 12 CFZtreated patients (75%) and 14 CDP-treated patients (82.4%) had complete or near-complete remission of skin lesions; intention-to-treat analysis showed no significant difference in the response rates between groups. Side effects, mainly skin and gastrointestinal events, were frequent in both groups, but no patients had to discontinue their treatment.Conclusion. These findings suggest that CFZ is equally as effective as CDP in controlling cutaneous lesions in SLE patients. However, we cannot exclude the possibility that the CFZ itself could be the cause of systemic lupus flare. Lupus erythematosus (LE) is an autoimmune disease that can exclusively affect the skin (cutaneous LE [CLE]) or can affect other systems as well (systemic LE [SLE]). Cutaneous lesions are classified as either specific or nonspecific. Lupus-specific cutaneous lesions are divided into acute, subacute, and chronic. Acute CLE includes malar and generalized maculopapular rashes. Subacute CLE includes the annular-polycyclic and papulosquamous (psoriasiform) variants. Chronic CLE includes discoid lupus erythematosus, lupus profundus, and LE tumidus, among others. Of the nonspecific LE cutaneous lesions, Raynaud's phenomenon, bullous LE, and vasculitic lesions are most common (1-3).In the literature, there are no reports of controlled, randomized clinical trials of a treatment strategy for SLE patients with cutaneous lesions. Based on clinical experience, antimalarial drugs are considered to be the first option for treatment of these patients (4). When a safe dosage of antimalarial drugs is used, the side effects are rare and include retinopathy, corneal deposition, disturbance of visual accommodation, nausea, vomiting, urticaria, hair discoloration, skin and mucosal hyperpigmentation, headache, tinnitus, dizziness, and myopathy, among others (5,6). Unfortunately, not all SLE patients with cutaneous lesions show a good response to antimalarial drugs. Treatment of the refractory cases includes use of thalidomide...

Clofazimine Analogs with Efficacy against Experimental Tuberculosis and Reduced Potential for Accumulation

“…This discoloration is evident within weeks of beginning treatment, fades months to years after the cessation of treatment, and occurs in a significant percentage of patients (16,33,42). CFM-induced skin discoloration has also been observed during treatment of M. avium complex and MDR TB infections, as well as during clinical trials to investigate the usefulness of CFM in inflammatory diseases, suggesting that this phenomenon is not leprosy specific (9,16,24,43). The reports available suggest that the intensity, duration, and prevalence of skin discoloration are dependent on the dose and duration of treatment.…”

Clofazimine Biocrystal Accumulation in Macrophages Upregulates Interleukin 1 Receptor Antagonist Production To Induce a Systemic Anti-Inflammatory State

“…In spite of its bioaccumulation, several clinical trials have established CFZ as a potentially useful therapeutic agent for treating a variety of chronic inflammatory diseases (17)(18)(19)(20)(21)(22). Furthermore, in vitro studies have shown that intracellular CFZ biocrystals dampen proinflammatory pathways while enhancing anti-inflammatory signals (23).…”

Cutaneous lupus erythematosus: Update of therapeutic options

“…[77][78][79][80] In 2005, a randomized, double-blind, controlled trial compared clofazimine (100 mg per day) with chloroquine (250 mg per day) in 33 patients with SLE and active skin lesions (ACLE, SCLE, localized and disseminated DLE). 81 At the end of the 6-month study, a complete response was seen in 18.8% of patients treated with clofazimine as compared with 41.2% of patients treated with chloroquine, but the difference was not significant. A good response was observed in 12 of 16 patients (75%) from the clofazimine group and in 14 of 17 patients (82.4%) from the chloroquine group.…”