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 Table of Contents  
Year : 2018  |  Volume : 13  |  Issue : 1  |  Page : 2-3

Getting around barriers in biologic treatment for systemic juvenile idiopathic arthritis patients in resource-poor countries

Department of Pediatrics, Division of Pediatric Rheumatology, Sri Ramachandra University, Chennai, Tamil Nadu, India

Date of Web Publication26-Feb-2018

Correspondence Address:
Dr. Mahesh Janarthanan
Department of Pediatrics, Division of Pediatric Rheumatology, Sri Ramachandra University, Chennai - 600 116, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-3698.226154

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How to cite this article:
Janarthanan M. Getting around barriers in biologic treatment for systemic juvenile idiopathic arthritis patients in resource-poor countries. Indian J Rheumatol 2018;13:2-3

How to cite this URL:
Janarthanan M. Getting around barriers in biologic treatment for systemic juvenile idiopathic arthritis patients in resource-poor countries. Indian J Rheumatol [serial online] 2018 [cited 2018 Mar 24];13:2-3. Available from: http://www.indianjrheumatol.com/text.asp?2018/13/1/2/226154

Systemic juvenile idiopathic arthritis (SJIA) is defined as arthritis associated with systemic features, typically quotidian spiking fevers for more than 2 weeks, accompanied by at least one of the following: an evanescent rash, arthritis, lymphadenopathy, serositis, or hepatosplenomegaly.

Elevated levels of pro-inflammatory cytokines – Interleukin 1 (IL-1), IL-6, IL8, IL18, macrophage inhibition factor, and tumor necrosis factor-alpha (TNF-α) – are characteristic of systemic onset JIA. It has been suggested that SJIA is mainly an IL-6 mediated disease. This hypothesis has been supported by the finding of elevated level of IL-6 in blood and synovial fluid of these patients. The level of Il-6 in these patients have been associated with fever spikes, systemic features, arthritis, and increased levels of acute phase reactants. The outcome in SJIA is generally poor compared to other types. Complications such as macrophage activation syndrome result in higher mortality rate in this disease.

High doses of steroids and nonbiologic disease-modifying agents have been traditionally used but have been less effective in this subtype of JIA.[1] Anti-TNF agents such as etanercept and infliximab are also not very effective in treating SJIA.[2]

With the advent of biologics such as anakinra (IL-1 receptor antagonist) and tocilizumab an anti-Il-6 agent in the last decade, the outcome for these patients has improved in developed countries.[3],[4] Newer anti-IL1 agents canakinumab and rilonacept have also been found to be beneficial in the treatment of SJIA patients, particularly in those with systemic features.[5],[6] The current trend in Western countries is to treat with biologics upfront to achieve early remission.

This is in stark contrast to the outcome of patients with SJIA in resource-poor countries as highlighted in this issue of the journal by Soponkanaporn et al.[7] Patients who failed DMARDS and needed biologics but were unable to afford them were shown to have persistent disease and poor outcomes. Tocilizumab, the biological agent that is useful in this scenario, is expensive when compared to other nonbiologic disease-modifying agents. The difficulties that children with SJIA and their carers face are manifold and uniform in all such countries. These include lack of access to appropriate tertiary care, absence of structured referral system or delayed referrals, easy access to alternative forms of medicine that are mostly not effective in this disease, lack of disease information in native languages, lack of psychosocial support, cost of biologic treatment, and poor awareness regarding the condition among public and medical fraternity. The final result is that children end up with crippling arthritis, amyloidosis, growth failure due to disease or steroid toxicity, and as a social burden.

The Indian scenario – according to guess estimates based on the population figures of 1.15 million in 2010 and worldwide prevalence of JIA of 0.07–10/1000, the number of patients with JIA in India alone would be around 1.3 million.[8] Compared to the West, the prevalence of SJIA is higher and accounts for about 8%–24% of JIA patients in India.[9],[10] This would mean that there are between 104,000 and 312,000 patients with SJIA in India alone. In all likelihood, only a few hundreds of patients receive tocilizumab in a systematic way. A significant number stop treatment after initiation of treatment with biologics mainly due to financial constraints.

Except for a couple of medical institutions in India where it is administered free of cost, tocilizumab remains a dream drug for a large number of children with severe disease. In addition, insurance companies do not agree to bear the cost of biologics either. As a result, there is limited published data regarding treatment of SJIA with biologics in India.

The first step toward creating awareness among medical professionals would be to include musculoskeletal examination or pediatric Gait Arms Leg Spine in the undergraduate medical curriculum. Few centers offer pediatric rheumatology training programs in India, and there is a need to increase the number of training centers and posts to narrow the trained physician–patient gap.

Second, a thalidomide derivative lenalidomide with lesser side effect profile than thalidomide is currently being used in the treatment of refractory SJIA. There is significant unpublished data on this subject in India. This data should be published as it offers the choice of an alternative to patients who cannot afford biological treatment and to physicians who deal with refractory SJIA patients.

Third, the possibility of development of anti-IL-6 biosimilars and the availability of tocilizumab subcutaneous injections in the future could bring down the overall cost.

Finally, just by the sheer size and population of the country, we have a very large cohort of patients. Taking a cue from European countries where multicenter international studies are done, our centers should come together, collate data, and publish. Developed nations could benefit from the large clinical pool, we have to offer and they in return could support research in identifying new potential therapeutic targets.

  References Top

Woo P, Southwood TR, Prieur AM, Doré CJ, Grainger J, David J, et al. Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis. Arthritis Rheum 2000;43:1849-57.  Back to cited text no. 1
Russo RA, Katsicas MM. Clinical remission in patients with systemic juvenile idiopathic arthritis treated with anti-tumor necrosis factor agents. J Rheumatol 2009;36:1078-82.  Back to cited text no. 2
Yokota S, Tanaka T, Kishimoto T. Efficacy, safety and tolerability of tocilizumab in patients with systemic juvenile idiopathic arthritis. Ther Adv Musculoskelet Dis 2012;4:387-97.  Back to cited text no. 3
Nigrovic PA, Mannion M, Prince FH, Zeft A, Rabinovich CE, van Rossum MA, et al. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: Report of forty-six patients from an international multicenter series. Arthritis Rheum 2011;63:545-55.  Back to cited text no. 4
Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med 2012;367:2396-406.  Back to cited text no. 5
Ilowite NT, Prather K, Lokhnygina Y, Schanberg LE, Elder M, Milojevic D, et al. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis. Arthritis Rheumatol 2014;66:2570-9.  Back to cited text no. 6
Soponkanaporn S, Jaovisidha S, Vilaiyuk S. Long-term outcomes and predictors of biologic treatment in systemic juvenile idiopathic arthritis in a single-center experience in Thailand. Indian J Rheumatol 2018;13:24-30.  Back to cited text no. 7
Habibi S, Aggarwal A, Ramanan AV. Paediatric rheumatology in India: Challenges and opportunities. Rheumatology (Oxford) 2012;51:962-3.  Back to cited text no. 8
Seth V, Kabra SK, Semwal OP, Jain Y. Clinico-immunological profile in juvenile rheumatoid arthritis – An Indian experience. Indian J Pediatr 1996;63:293-300.  Back to cited text no. 9
Kunjir V, Venugopalan A, Chopra A. Profile of Indian patients with juvenile onset chronic inflammatory joint disease using the ILAR classification criteria for JIA: A community-based cohort study. J Rheumatol 2010;37:1756-62.  Back to cited text no. 10


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