Background Systemic juvenile idiopathic arthritis (sJIA), though well responsive to corticosteroids (1), but toxicity limit their prolonged usage. Other disease modifying anti rheumatic drugs (DMARDs) have been tried to limited effect (1). Only the newer biologic agents (Anakinra, Tocilizumab) are promising (1,2), but in a developing country like India, accessibility and prohibitive costs limit their use. We started trying Cyclosporine, a potent immunosuprressive agent for the cost benefit in steroid dependent or refractory sJIA specially in those who relapsed with predominant systemic symptoms. Here, we present a series of 15 cases refractory sJIA most of whom were successfully treated with oral Cyclosporine in conjunction with methotrexate ± low dose steroids.
Objectives 1. To assess the efficacy of Cyclosporine in patients of steroid unresponsive or steroid dependent Systemic JIA. 2. To evaluate the optimum dosing and blood level to achieve and maintain remission.
Methods Clinical records of children fulfilling the diagnostic criteria of sJIA admitted at the Institute of Child Health, Kolkata during the time period July 2009 to November 2015 were reviewed. The data collected included details of clinical and laboratory features, treatment and outcome. In this prospective study a total of 82 sJIA was diagnosed. 15 were refractory and included as a candidate for cyclosporine therapy.
Criteria for initiating Cyclosporine: sJIA relapsing frequently (at least 3 times) on withdrawing or attempting to taper off steroids, in spite of being on Methotrexate +/− Hydroxychloroquine.
Results Among the 15 patients of frequently relapsing, steroid dependent sJIA, 13 responded to cyclosporine and Steroid could be withdrawn completely after a mean duration of 6.15 months of starting Cyclosporine.
Among this 13, 11 never relapsed after initiation of Cyclosporine and 2 relapsed but managed with a short course of steroid. So we achieved a permanent remission rate of 73% (P value0.02) with a mean follow up of 15 months after starting cyclosporine.
1. Off Steroid, off Cyclosporine -11 (9 never relapsed, 2 relapsed but responded to short course steroids)
2. Off Steroid, on Cyclosporine-2 (never relapsed)
3. Did not respond to Cyclosporine -2
The mean dose of Cyclosporine to achieve the remission was 3.9 mg/kg/day.
The mean blood level in which remission was induced was 138.4ng/ml.
There was no significant side effect noted except hirsuitism in one and another one developed transient hypertension.
Conclusions 1. Cyclosporine was found to be effective in almost 75% of frequently relapsing steroid dependent sJIA to achieve and maintain remission.
2. Cyclosporine was found to be a cheaper alternative to Tocilizumab as the average cost of therapy for a 20kg patient on Cyclosporine was found to be 10,000 INR (143 EURO)/patient over a 6 months period; which would amount to 100,000 INR (1430 EURO)/patient with Tocilizumab for the same duration (Anakinra not available in India).
Timothy Beukelman et al, 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features.
Fabrizio De Benedetti et al Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis. N Engl J Med 2012;367:2385–95.DOI: 10.1056/NEJMoa1112802.
Disclosure of Interest None declared