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• Successful treatment of refractory adult Still's disease with IL-6 receptor blockade
  Xavier Puechal
  Published on: 17 January 2011

• Published on: 17 January 2011

  Successful treatment of refractory adult Still's disease with IL-6 receptor blockade

  • Xavier Puechal, MD, PhD
  • Other Contributors:
    • CRI (Club Rhumatismes et Inflammation)

  Dear Editori,

  We have read with interest the letter of Rech et al. on 3 patients with adult's Still disease (ASD) who experienced systemic and arthritis improvement while being treated with tocilizumab (TCZ) (1).

  We would like to add that a previously published cohort study has reported the results of a tocilizumab treatment in all ASD patients treated in France with TCZ during a three-year period, after failure...

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  Dear Editori,

  We have read with interest the letter of Rech et al. on 3 patients with adult's Still disease (ASD) who experienced systemic and arthritis improvement while being treated with tocilizumab (TCZ) (1).

  We would like to add that a previously published cohort study has reported the results of a tocilizumab treatment in all ASD patients treated in France with TCZ during a three-year period, after failure to all available therapies (2).

  To be eligible to receive off-label TCZ for ASD in France between July 2006 and July 2009, patients had to be enrolled in a specific protocol of the French Agency for the Safety of Health Products (AFSSAPS).
  The study population consisted of patients who fulfilled the Yamagushi criteria for ASD (3) and who had to present persistent active arthritis and/or systemic involvement resistant to therapies including corticosteroids, methotrexate, anakinra and anti-TNFa drugs. Data were collected prospectively from physicians in charge of the patients. All patients receiving at least one infusion of TCZ during the study period were evaluated. The main outcome measures were the EULAR improvement criteria and resolution of systemic symptoms at 3 and 6-month follow-up (4).

  Fourteen patients suffering from intractable refractory ASD were included in the cohort. All had chronic arthritis; radiological examination showed irreversible joint damage in eight patients. All patients had experienced failure or intolerance with methotrexate and anakinra and twelve with at least one anti-TNF drug. At baseline, all patients were receiving prednisone at a mean dose of 23.3 mg/day. Based on a 28 joint count, mean tender joints were 10.5, swollen joints 7.9 and the mean DAS28 was 5.61. At baseline, in addition to arthritis, recurrent systemic involvement, including fever and rash, was present in seven patients. Median ESR was 36.5 mm/1st hour and CRP was 5.2 mg/dL.

  Eleven patients successfully completed the 6-month study. One withdrew due to necrotizing angiodermatitis, another due to chest pain at each TCZ infusion and a third due to systemic flare. A rapid resolution of systemic manifestations and arthritis was observed in most cases. The mean DAS28 dropped from 5.61 to 3.21 and 2.91 at 3 and 6-month follow-up visits, respectively. A good EULAR response was achieved in 64% (9/14) of patients at three and six months. EULAR remission (DAS28<2.6) was achieved in 36% of patients (5/14) at three months and in 57% (8/14) at six months. The good EULAR response observed in two thirds of patients at three months was due to improvement of all disease activity scores: at six months, there was a 60% improvement in the number of tender joints, the number of swollen joints and the mean visual assessment score for patient global health. Resolution of systemic symptoms, including fever and eruption, was observed for 86% of patients (6/7) at three and six months.
  Moreover, the mean prednisone dose was reduced to a mean of 13.0 mg/day at three months and to a mean of 10.3 at six months.
  Thus, in most of our patients with refractory disease, response to TCZ treatment was rapid and sustained. The high observed rate (57%) of arthritis remission at six months is of particular interest in these patients. Of the seven patients with active systemic features at the start of TCZ treatment, all but one showed resolution of these symptoms. Notably, TCZ had a corticosteroid-sparing effect since these meaningful improvements were observed despite a 56% mean reduction in corticosteroid dose after starting treatment.

  We conclude that our cohort of patients with refractory ASD has demonstrated that an IL-6 inhibiting therapeutic approach TCZ was effective against systemic involvement of the disease in almost all patients and led to arthritis remission in half the patients, showing a marked corticosteroid-sparing effect and an acceptable tolerance profile.
  TCZ is a promising new treatment which should be further evaluated in ASD.

  References

  1. Rech J, Ronneberger M, Englbrecht M, et al. Successful treatment of adult-onset Still'S disease refractory to TNF and IL-1 blockade by IL-6 receptor blockade. Ann Rheum Dis 2011;70:390-2.

  2. Puechal X, de Bandt M, Berthelot JM, et al. Tocilizumab in refractory adult Still's disease. Arthritis Care Res (Hoboken) 2011;63:155-9.

  3. Yamaguchi M, Ohta A, Tsunematsu T, et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol 1992;19:424-30.

  4. van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 1998;41:1845-50.

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  Conflict of Interest:
  None declared.

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