Jump to comment:

• Infliximab therapy for refractory adult-onset Still's disease
  Petros P Sfikakis
  Published on: 14 February 2005
• Still's disease and anti-TNF alpha therapy: the pediatric experience
  Pierre Quartier
  Published on: 9 February 2005

• Published on: 14 February 2005

  Infliximab therapy for refractory adult-onset Still's disease

  • Petros P Sfikakis
  • Other Contributors:
    • Alexios Kokkinos, Alexios Iliopoulos, George D Kitas

  Dear Editor,

  We read with interest the observational, retrospective study by Fautrel and colleagues on the efficacy of anti-TNFƒÑ agents (aTNF) in refractory adult onset Still¡¦s disease (AOSD) [1].

  The authors conclude that aTNF is not as effective in AOSD as in rheumatoid arthritis (RA) or the spondyloarthrotopathies and may be helpful only in some AOSD cases. This conclusion cannot be fully supporte...

  Show More

  Dear Editor,

  We read with interest the observational, retrospective study by Fautrel and colleagues on the efficacy of anti-TNFƒÑ agents (aTNF) in refractory adult onset Still¡¦s disease (AOSD) [1].

  The authors conclude that aTNF is not as effective in AOSD as in rheumatoid arthritis (RA) or the spondyloarthrotopathies and may be helpful only in some AOSD cases. This conclusion cannot be fully supported by the results presented and we would like to suggest an alternative interpretation.

  Firstly, it is difficult to draw parallels between AOSD and RA studies, due to differences in the nature of these conditions, severity of disease on inclusion, response criteria used, and overall study designs. If anything, complete remission with aTNF appears commoner in this study of AOSD than in multiple RA trials. Secondly, besides the retrospective design, there are other limitations that would also suggest that any conclusions should be viewed with caution. These include the significant heterogeneity of concomitant treatment, the exclusively clinician-based, subjective, assessment of response, possible slight overrepresentation of females and inclusion of 3 patients that may have had juvenile Still¡¦s disease [2] rather than AOSD.

  More importantly, there may be a differential response to the two aTNF agents used. Excluding patients with juvenile Still¡¦s disease, Etanercept was used as the first agent in 9 AOSD patients: 2 failed to respond, 6 achieved partial remission, and 1 achieved complete remission (with concomitant prednizolone 80 mg/day!). In contrast, in the 9 AOSD patients who received infliximab as the first agent, there were 5 partial remissions, 4 complete remissions and no failures (chi-squared test for trend=3.846, P=0.0499). Infliximab was given in one additional AOSD patient after failure of Etanercept and resulted in partial response, while 2 other patients had also Infliximab-induced partial responses after a similar Etanercept-induced response. It is interesting that the only 3 patients who failed to respond to Infliximab are those who could be classified as juvenile Still¡¦s disease.

  Differential efficacy of aTNF agents is well-described in Crohn¡¦s disease [3], may also occur in Adamantiades-Behcet¡¦s disease [4, 5] and, we suggest, AOSD. Allowing for reporting bias, all of the AOSD cases reported thus far appear to have had benefit from Infliximab [1, 6-10], even cases refractory to pulse steroid therapy. We suggest that, on current evidence, Infliximab is a very reasonable treatment choice in refractory AOSD. The possibility of a differential response between Infliximab and Etanercept in AOSD requires further investigation.

  References

  (1). Fautrel B, Sibilia J, Mariette X, Combe B. Tumour necrosis factor (alpha) blocking agents in refractory adult Still¡¦s disease: an observational study of 20 cases. Ann Rheum Dis 2005; 64:262-6

  (2). Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H et al. J Rheumatol 1992; 19: 424-30

  (3). van Deventer SJH. Transmembrane TNF-alpha, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn's disease. Gastroenterology 2001; 121:1242-6

  (4). Sfikakis PP. Behcet's disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis 2002; 61(suppl 2):ii51-3

  (5). Sfikakis PP, Kaklamanis PH, Elezoglou A, Katsilambros N, Theodossiadis PG, Papaefthimiou S, et al. Infliximab for recurrent, sight- threatening ocular inflammation in Adamantiades-Behcet disease. Ann Intern Med 2004; 140: 404-6

  (6). Cavagna L, Caporali R, Epis O, Bobbio-Pallavicini F, Montecucco C. Infliximab in the treatment of adult Still's disease refractory to conventional therapy. Clin Exp Rheum 2001; 19: 329-32

  (7). Caramaschi P, Biasi D, Carletto A, Bambara LM. A case of adult onset Still's disease treated with infliximab. Clin Exp Rheumatol 2002; 20: 113

  (8). Dechant C, Schauenberg P, Antoni CE, Kraetsch HG, Kalden JR, Manger B. Longterm outcome of TNF blockade in adult-onset Still's disease. Dtsch Med Wochenschr 2004; 129: 1308-12

  (9). Bonilla Hernan MG, Cobo Ibanez T, de Miguel Mendieta E, Martin- Mola E. Infliximab (anti-TNF alpha) treatment in patients with adult Still¡¦s disease. Experience in 2 cases. An Med Interna 2004; 21: 23-6

  (10). Kokkinos A, Iliopoulos A, Greka P, Efthymiou A, Katsilambros N, Sfikakis PP. Successful treatment of refractory adult-onset Still's disease with infliximab. A prospective, non-comparative series of four patients. Clin Rheumatol 2004; 23: 45-9.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top
• Published on: 9 February 2005

  Still's disease and anti-TNF alpha therapy: the pediatric experience

  • Pierre Quartier, MD
  • Other Contributors:
    • Anne-Marie Prieur

  Dear Editor,

  Fautrel et al [1] recently reported the cases of 20 adults with Still's disease who were treated with TNF alpha blocking agents. Most patients only achieved partial remission and there were only 2 cases of sustained remission of more than one year, which contrasts with the much higher response rates observed in patients with rheumatoid arthritis.

  In this paper, the authors never refer...

  Show More

  Dear Editor,

  Fautrel et al [1] recently reported the cases of 20 adults with Still's disease who were treated with TNF alpha blocking agents. Most patients only achieved partial remission and there were only 2 cases of sustained remission of more than one year, which contrasts with the much higher response rates observed in patients with rheumatoid arthritis.

  In this paper, the authors never refer to the pediatric experience. However, they indicate that the disease had a childhood onset in 4 of their patients and they insist on the scantiness of available data in adults. Although the disease is also rare in children, several studies had been published reporting the experience of etanercept treatment in more than one hundred patients with systemic-onset juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA), i.e. childhood-onset Still's disease. [2-5] Moreover, we and others showed that these patients were significantly less responsive to anti-TNF alpha therapy than patients with other forms of JIA. [4-5]

  When dealing with the treatment of rare diseases, pediatricians and rheumatologists have to consider each others' experience.

  References

  (1). Fautrel B, Sibilia J, Mariette X, Combe B. Tumour necrosis factor a blocking agents in refractory adult Still's disease: an observational study of 20 cases. Ann Rheum Dis. 2005;64:262-266.

  (2). Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med. 2000;342:763-9.

  (3). Lovell DJ, Giannini EH, Reiff A, Jones OY, Schneider R, Olson JC, et al. Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter, open-label, extended-treatment trial. Arthritis Rheum. 2003;48:218-26.

  (4). Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M, et al. Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum. 2003;48:1093-101.

  (5). Horneff G, Schmeling H, Biedermann T, Foeldvari I, Ganser G, Girschick HJ, et al. The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis. 2004;63:1638-44.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top