Etanercept in four children with therapy-resistant systemic juvenile idiopathic arthritis

Paediatric Rheumatology/Series Editor: P. Woo

R. ten Cate1,3,, L. W. A. van Suijlekom-Smit3, D. M. C. Brinkman1, W. P. Bekkering2, C. J. A. Jansen-van Wijngaarden4 and J. M. Vossen1

Departments of
1 Paediatrics and
2 Physical Therapy, Leiden University Medical Centre and Departments of
3 Paediatrics and
4 Physical Therapy, University Hospital Rotterdam/Sophia's Children's Hospital, The Netherlands

Letter to the Editor

SIR, Systemic juvenile idiopathic arthritis (sJIA) is a difficult disease to treat. Drugs that can be effective, such as steroids and methotrexate (MTX), often lead to complications. Some patients are truly therapy-resistant, meaning that the combination of non-steroidal anti-inflammatory drugs (NSAIDs), steroids, MTX up to 1 mg/kg/week and cyclosporin A (CyA) (5 mg/kg/day) [1] fails to induce remission or leads to unacceptable adverse effects. Because of the positive results of the North American Pediatric Rheumatology Collaborative Study Group [2], we treated four children with sJIA who were therapy-resistant or unable to tolerate the cytostatic drugs prior to inclusion for autologous bone marrow transplantation [3] with etanercept (0.4 mg/kg twice weekly, subcutaneously). The effect was evaluated between 3 and 6 months after starting etanercept using the Paediatric Rheumatology International Trials Organization (PRINTO) definition of improvement [4] (Table 1Go).


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TABLE 1.  PRINTO variables in four children with sJIA treated with etanercept

 
Case 1. A girl was diagnosed as having sJIA at the age of 10 months. NSAIDs, steroids and MTX were stopped after 2 yr. A relapse occurred which did not respond to the same treatment. CyA was not tolerated. Etanercept was started at the age of 9 yr. She improved but her arthritis became active again 5 months later. Etanercept was continued and disease activity decreased. Steroids and NSAIDs were discontinued.

Case 2. A 9-yr-old girl who had been diagnosed with sJIA at the age of 4 yr continued to have active polyarthritis despite NSAIDs, steroids and MTX. Several thoracic vertebrae collapsed with osteoporosis. CyA had no effect. At the age of 9 yr etanercept was started. She improved and steroid treatment was stopped, but her disease flared after 6 months, requiring temporary reintroduction of steroids. Currently she is well with low disease activity and still on etanercept and NSAIDs.

Case 3. A boy was diagnosed as having sJIA at the age of 3 yr. After a varicella infection, there was full remission. A relapse occurred which did not respond to steroids and MTX, and osteoporosis and radiological joint destruction resulted. Three months after the introduction of etanercept, none of the PRINTO parameters had improved. Etanercept was discontinued.

Case 4. A boy was diagnosed as having sJIA at the age of 5 yr. His disease did not respond to NSAIDs, steroids and MTX. CyA was not tolerated. At the age of 7 yr etanercept was started because of polyarthritis. This treatment improved pain scores, but left all other PRINTO parameters unchanged. After discontinuation of the etanercept his pain and well-being deteriorated. After the introduction of etanercept he quickly improved and steroids were reduced. Currently he is undergoing experimental autologous bone marrow transplantation because of ongoing disease activity. Etanercept was discontinued shortly before immunoablation.

We report the use of etanercept in four children with therapy-resistant sJIA. The first two patients improved according to the PRINTO definition of improvement. Patient three is regarded as a non-responder. Patient four showed a marked improvement in pain, both on physical examination and on the visual analogue scale. These results differ from those of Lovell et al. [2], 70% of whose patients (33% had a systemic onset) improved. Arthritis remained a problem in two of our patients, but in one there was a striking positive effect on pain and well-being. In three children steroids could be reduced. The discontinuation of steroids is of major importance, especially as etanercept seems to lack short-term side-effects. The place of etanercept in sJIA remains to be determined. In order to balance the positive effects, side-effects and costs of etanercept, further studies in children with JIA are required.

Notes

Correspondence to: R. ten Cate, Leiden University Medical Centre, Department of Paediatrics, J6-S, PO Box 9600, 2300 RC Leiden, The Netherlands. Back

References

  1. Reiff A, Rawlings DJ, Shaham B, Franke E, Richardson L, Szer IS, Bernstein BH. Preliminary evidence for cyclosporin A as an alternative in the treatment of recalcitrant juvenile rheumatoid arthritis and juvenile dermatomyositis. J Rheumatol1997;24:2436–43.[ISI][Medline]
  2. Lovell DJ, Giannini EH, Reiff A et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med2000;342:763–9.[Abstract/Free Full Text]
  3. Wulffraat N, van Royen A, Bierings M, Vossen J, Kuis W. Autologous haemopoietic stem-cell transplantation in four patients with refractory juvenile chronic arthritis. Lancet1999;353:550–3.[ISI][Medline]
  4. Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum1997;40:1202–9.[ISI][Medline]
Accepted 6 July 2001





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