TOPLINE:

Adding mepacrine to hydroxychloroquine (HCQ)-based treatments was effective in improving remission rates, reducing disease activity, and enabling steroid tapering in patients with active systemic lupus erythematosus (SLE) unresponsive to HCQ-based treatments. It caused few and mild side effects.

METHODOLOGY:

• Researchers conducted an observational study to evaluate the efficacy of mepacrine as add-on therapy in patients with active SLE with cutaneous, articular, and/or serosal activity unresponsive to HCQ-based regimens.
• They analyzed data of 106 mepacrine treatment episodes in 103 patients with SLE (mean age, 40.7 years; 89.6% female; 85.8% White individuals) identified from the Lupus-Cruces database; all patients received HCQ (200 mg/d) plus prednisone (mean, 6 mg/d) at baseline.
• Two groups were identified: a single-therapy group that received HCQ and prednisone only (n = 56) and a multiple-therapy group that received HCQ and prednisone plus immunosuppressives and/or biologics (n = 50). The mean starting dose of mepacrine was 76.7 mg/d vs 87.0 mg/d in the single-therapy vs multiple-therapy groups.
• The primary efficacy outcome was the achievement of the definition of remission in SLE (DORIS) 6 months after mepacrine initiation.
• The secondary outcomes were clinical or no response to mepacrine and reduction in prednisone dosage. Mepacrine-related adverse effects and treatment discontinuation were also assessed.

TAKEAWAY:

• At 6 months, 71% of all patients achieved DORIS remission after adding mepacrine, with remission rates of 79% vs 62% in the single-therapy vs multiple-therapy groups.
• Disease activity decreased, with mean SLE Disease Activity Index scores declining in the whole group from 6.7 at baseline to 1.9 at 6 months (P < .001); similar reductions were seen in the two treatment groups.
• The overall mean prednisone dose decreased from 6 mg/d to 4.3 mg/d at 6 months (P < .001), with comparable reductions in the two treatment groups.
• Adverse effects occurred in 17% of patients, with 6.6% of patients discontinuing treatment due to toxicity. The most commonly occurring side effects were gastric upset and severe yellowish skin discoloration.

IN PRACTICE:

“Our results support the use of [mepacrine] as an early add-on therapy to HCQ in patients with active SLE at cutaneous, articular, and/or serosal levels, although patients with more complex therapeutic schemes can also benefit from this safe and well-tolerated drug,” the authors of the study wrote.

SOURCE:

The study was led by Beatriz Marín-García, Biobizkaia Health Research Institute, Barakaldo, Spain. It was published online on December 23, 2025, in Lupus Science & Medicine.

LIMITATIONS:

A control group was lacking. The study primarily comprised White patients with access to free healthcare.

DISCLOSURES:

One author reported receiving support from the Department of Education of the Basque Government. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.