Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus.

OBJECTIVE: To evaluate the safety and clinical efficacy of administering an anti-interleukin-10 (anti-IL-10) monoclonal antibody (mAb) to systemic lupus erythematosus (SLE) patients with active and steroid-dependent disease. In addition, we sought to assess the effects of in vivo IL-10 neutralization on biologic markers of SLE. METHODS: Treatment consisted of 20 mg/day intravenous administration of an anti-IL-10 murine mAb (B-N10) for 21 consecutive days, with a followup period of 6 months. Six patients were studied. RESULTS: Treatment was safe and well tolerated. All patients developed antibodies against B-N10. Cutaneous lesions and joint symptoms improved in all patients beginning during B-N10 administration and continuing to month 6. The SLE Disease Activity Index decreased from a mean +/- SEM of 8.83+/-0.91 on day 1 to 3.67+/-0.67 on day 21 (P = 0.001), 1.50+/-0.84 at month 2, and 1.33+/-0.80 at month 6 (P<0.001). At the end of followup, the disease was clinically inactive in 5 of the 6 patients. Prednisone administration was decreased from a mean +/- SEM of 27.9+/-5.7 mg/day on day 1 to 9.6+/-2.0 mg/day at month 6 (P<0.005). Activity of immune and endothelial cells rapidly decreased, as assessed by the early evolution of several biologic markers. CONCLUSION: This is the first report of IL-10 antagonist administration to humans. The study shows the involvement of IL-10 in the pathogenesis of SLE, and indicates that the use of IL-10 antagonists may be beneficial in the management of refractory SLE.

Remission of systematic lupus erythematosus.

The occurrence and characteristics of remissions in patients with systematic lupus erythematosus (SLE) have not been determined. We therefore studied this in a cohort of 667 patients and found that 156 patients had achieved at least 1 period of 1 year or more of treatment-free clinical remission. This represents an incidence density of 0.028 new cases/person/year. Remission occurred within the first 2 years of disease in 62 patients. The mean duration of first remission was 4.6 years (range, 1-21 yr), and 81 patients were still in the initial remission up until cutoff time. Half of the remaining 75 patients who flared after achieving remission have not entered again in remission. Twenty-six of the 38 patients who did remained in remission, and the remaining 12 had subsequent flares and remissions. Treatment-free remission accounted for a mean of 5.8 years, corresponding to half the time of follow-up. Remission was not limited to patients with mild disease: at least 41 patients achieved remission despite renal involvement, 19 had had neuropsychiatric lupus, 15 had had thrombocytopenia, and 8 had had hemolytic anemia. We also found that the longer the time lapse between the initial manifestation and the diagnosis of SLE, the less likely it was for a patient to enter into remission. There was a continuous increase in likelihood of achieving a first remission from the beginning of disease up to 30 years of disease duration, when it reached 70%. Patients who achieved remission had increased survival, independently of the effect of other disease manifestations that cause increased mortality. We conclude that a significant proportion of patients with SLE, including those with severe organ involvement, may become symptom-free and in need of no more medication, perhaps indefinitely. Our findings support the notion that, in general, SLE is a more benign disease than previously considered.