ATC codes: Pending
Systemic lupus erythematosus ICD11 code: 4A40.0Z
Medicine type
Chemical agent
List type
Oral > Solid: 200 mg (as sulfate) (EMLc)
EML status history
First added in 2011 (TRS 965)
Children (1 month - 12 years)
Therapeutic equivalence
The recommendation is for this specific medicine
Patent information
Patents have expired in most jurisdictions
Summary of evidence and Expert Committee recommendations
At its 2009 meeting, the Committee had requested a review of the medicines needed for the treatment of juvenile idiopathic arthritis (JIA) in children, as it did not endorse any of the medicines currently listed. The current EMLc includes acetylsalicylic acid to treat systemic onset JIA, Kawasaki disease, and rheumatic fever (Complementary List), as well as immunoglobulins (intravenous Ig) for Kawasaki disease. A review was prepared by P Gowdie (Royal Children’s Hospital, Melbourne, Australia) to identify priority rheumatic conditions in children, treatment options, evidence for efficacy and safety, and to make recommendations for the inclusion of medicines. The Committee noted that the most frequent condition in children is JIA, with three main forms: systemic onset, polyarticular, and oligo-monoarticular. Other conditions of interest are juvenile dermatomyositis/polymyositis (JDM), and systemic lupus erythematosus (SLE), but these are infrequent in children. Other chronic arthritic diseases affecting children such as acute rheumatic fever, Lyme disease, post-streptococcal reactive arthritis, Kawasaki disease, and other vasculitides were not discussed in the application. The Committee noted that the following pharmacological classes were used: NSAIMs for the management of symptoms; corticosteroids at immunosuppressive doses (especially for paediatric SLE and JDM); and DMARDs which include methotrexate, cyclophosphamide, azathioprine, cyclosporine, mycophenolate, leflunomide, sulfasalazine, and chloroquine or hydroxychloroquine. DMARDs aim to control disease activity, prevent irreversible organ damage, and decrease the burden of the disease or steroid treatment. The Committee first considered whether these conditions represent a priority health problem for the population. Estimates of prevalence are available for JIA in developed countries (from 7 to 401 per 100 000 children) and this condition can produce a high burden of disease if it continues into adulthood with severe disability or the need for joint replacement. Juvenile dermatomyositis, on the other hand, is a rare disease and if treated appropriately with high doses of steroids, immunosuppressants and supportive care, can result in little disability. The prevalence of paediatric SLE, a chronic, life-threatening disease, ranges between 0.36 and 0.9 per 100 000 children. The Committee noted the lack of specific data in children affected by chronic arthritis or inflammatory systemic diseases in developing countries. The Committee evaluated the evidence provided in the review for each of the medicines. A summary of the considerations is provided in Table 1 (page 14, TRS 965) and full details of the clinical evidence are in the application. For hydroxychloroquine (HCQ), currently not in the EML, the Committee considered that there is evidence for efficacy and safety in adult SLE: a RCT (Canadian Hydroxychloroquine Study Group) showed that adult patients assigned to the placebo group had a significantly higher relative risk of flare and shorter time to flare compared to those patients who continued HCQ; and a recent systematic review of 95 articles (all ages) that concluded that there was evidence that antimalarials used in lupus prevent lupus flares and increase long-term survival of patients with SLE, and moderate evidence of protection against irreversible organ damage, thrombosis, and bone mass loss, with infrequent and reversible toxicity (1). The low cost of HCQ is an advantage for a systematic prescription in SLE patients. The Committee also noted that the Childhood Arthritis and Rheumatology Research Alliance (CARRA) recommends hydroxychloroquine for milder cases of juvenile dermatomyositis and cases mainly characterized by rash (2). In children the recommended dose is 3–5 mg/kg per day with a maximum of 400 mg (as once or twice daily with food). The Committee noted that HCQ is generally safe, including during pregnancy and breastfeeding. Common adverse effects include gastrointestinal (GI) and central nervous system (CNS) disturbances. The most serious irreversible adverse effect, however, is retinal (macular) toxicity, which can lead to blindness. The maximum safe daily dose in adults is 6.5 mg/kg, but is not defined in children (European Union, EU, product information). Detection of early retinal changes requires yearly monitoring and, if discovered, should lead to discontinuation of HCQ. The Committee considered that there is evidence of effectiveness for hydroxychloroquine in SLE and recommended its inclusion in the EMLc Complementary List with availability of ophthalmologic monitoring as a condition for its use. A review in respect of adults would be prepared for the next meeting. References: 1. Ruiz-Irastorza G et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Annals of the Rheumatic Diseases, 2010, 69(1):20–28. 2. Stringer E et al. Treatment approaches to juvenile dermatomyositis (JDM) across North America: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Treatment Survey. The Journal of Rheumatology, 2010, 37(9):1953–1961.