A randomized, placebo-controlled trial of hydroxychloroquine in incomplete lupus.

OBJECTIVES Patients with features of systemic lupus erythematosus (SLE) who do not fulfill classification criteria can be designated as incomplete lupus (ILE). This condition includes individuals with a high risk of progression to SLE. Treatment of ILE may reduce symptoms, severity and incidence of SLE. METHODS Hydroxychloroquine (HCQ) was chosen as an ILE intervention for a randomized, double-blind trial to determine whether rate of accumulation of SLE features defined by the 2012 SLICC criteria could be reduced. ILE was defined as ANA positivity with 1-2 additional criteria. Patients 15-49 years old were eligible. Randomization was 1:1 HCQ to placebo. Evaluations were at 3-month intervals over 24 months. Meeting SLICC classification sooner required exit. RESULTS Participants (n=187) were randomized at 7 sites. After excluding 7 patients who met SLE classification at baseline when screening laboratory data were completed, 180 patients were analyzed: 92 on HCQ and 88 on placebo. The mean age was 33 years, 91.1% were female and 74.4% were white. SLE classification developed in 24 (13.3%); another 24 developed additional criteria but did not meet classification. The rates of acquisition of SLICC criteria and progression to SLE were similar in the two groups (P=0.72 and P=0.98, respectively). Development of SLE was associated with new malar rash, oral ulcers, joint tenderness or pleurisy (P<0.04). CONCLUSION While SMILE did not show effects of HCQ on ILE progression, the results offer insights into SLE risk in the ILE population. With development of biomarkers, designing targeted prevention strategies should be feasible.