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• Authors' response re:Abatacept in relapsing polychondritis
  Stanford Peng
  Published on: 26 July 2013
• Abatacept in relapsing polychondritis
  Guillaume Moulis
  Published on: 23 July 2013

• Published on: 26 July 2013

  Authors' response re:Abatacept in relapsing polychondritis

  • Stanford Peng, MD
  • Other Contributors:
    • Donald Rodriguez

  Dear Editor,

  We were pleased to learn of Moulis et al.'s update on their experience with abatacept in three RP patients, particularly since their disease manifestations reflected the same manifestations suggested in our study to be of greatest interest for abatacept: chondritis and peripheral arthritis. Interestingly one patient achieved a complete, while another achieved only a partial, corticosteroid-sparing...

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  Dear Editor,

  We were pleased to learn of Moulis et al.'s update on their experience with abatacept in three RP patients, particularly since their disease manifestations reflected the same manifestations suggested in our study to be of greatest interest for abatacept: chondritis and peripheral arthritis. Interestingly one patient achieved a complete, while another achieved only a partial, corticosteroid-sparing response, and the third patient could not taper corticosteroids at all. We note that the patient who achieved a complete response was given abatacept in combination with dapsone and methotrexate, while the other two appear to have been given abatacept as only monotherapy. In that context, it is notable that the one subject in our study who developed an excellent long-term response to abatacept was taking mycophenolate mofetil concomitantly (subject 002), while another with a less durable response was taking only prednisone without a concomitant immunosuppressant (subject 003) (1), suggesting that combination therapy involving abatacept and a conventional immunomodulatory drug may provide greater efficacy, as described with abatacept in rheumatoid arthritis [2].
  At the same time, though, the two subjects in our study who developed severe relapses warranting study discontinuation were in fact already taking concomitant immunosuppressive drugs (subjects 001 and 004; leflunomide and mycophenolate mofetil, respectively) - but as previously recognized these patients had more severe disease, and/or might have benefitted more from an intravenous instead of subcutaneous abatacept dosing regimen as well as bridging therapy with corticosteroids. These observations further reinforce an importance relevance of costimulation to the pathogenesis of at least part of the chondritis and arthritis of RP, but at the same time remind us of our incomplete understanding of its disease and therapeutic context. We hope that ongoing observations and study of abatacept in this challenging disease will continue to provide further insights in this regard.

  References

  1. Peng SL, Rodriguez D. Abatacept in relapsing polychondritis. Ann Rheum Dis 2013;72:1427-9. 2. Buch MH, Vital EM, Emery P. Abatacept in the treatment of rheumatoid arthritis. Arthritis Res Ther 2008;10:S5.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 23 July 2013

  Abatacept in relapsing polychondritis

  • Guillaume Moulis
  • Other Contributors:
    • Gregory Pugnet, Laurent Sailler, Leonardo Astudillo, and Philippe Arlet

  Dear Editor,

  We read with great interest the open clinical trial of four relapsing polychondritis (RP) patients treated with abatacept by Peng and Rodriguez recently published in the Annals of the Rheumatic Diseases (1). Indeed, as the authors pointed out, there is rational to block T-cell pathway in this disease, though the biologic agents most used as second-line therapy after corticosteroids (CS) are pro-inflamm...

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  Dear Editor,

  We read with great interest the open clinical trial of four relapsing polychondritis (RP) patients treated with abatacept by Peng and Rodriguez recently published in the Annals of the Rheumatic Diseases (1). Indeed, as the authors pointed out, there is rational to block T-cell pathway in this disease, though the biologic agents most used as second-line therapy after corticosteroids (CS) are pro-inflammatory cytokines blockers as TNF inhibitors or tocilizumab (2). Of note, rituximab seems not efficient in this disease (3).

  Despite this rational, the study by Peng and Rodriguez is the first report of abatacept use in RP since we reported a first case in 2010 (4). Results from this nice small clinical trial using abatacept subcutaneously at the dose of 125 mg weekly are mitigated: three patients experienced a considerable improvement on ENT chondritis and on swollen and tender joint counts. Nevertheless, two patients developed severe central nervous system and pulmonary involvement at week 2 and 8 respectively. Both had a history of such organ involvement. CS-sparing is an important issue not assessed in this trial but three patients were exposed to only 10 mg of prednisone per day, and the last one was not exposed to CS at abatacept initiation. The follow-up was limited to 24 weeks.

  We would like to share our experience as to complete these results. Indeed, three adult RP patients have been treated with abatacept in our department - the data of two of them until mid-2012 have been previously presented (5). In all cases, abatacept was started because of CS-dependant or CS-resistant disease. All had ENT chondritis and peripheral arthritis without internal organ involvement. As ethically mandatory in France, the decision to treat these patients with off-label abatacept was decided during a multidisciplinary board associating specialist physicians and pharmacists. The patients gave their formal consent after explanation of the expected benefit-to-risk ratio. Abatacept was used intravenously at the dose of 750 mg at Day0, Day14 and Day30 and then monthly. Efficacy and adverse drug reactions (ADRs) were colligated in the medical files. Complete response, partial response and no response were respectively defined as the complete disappearance, the improvement and the lack of improvement (or the worsening) of clinical symptoms according to the physician assessment.

  The first patient was a 53-year-old woman who had CS-resistant disease which had failed to dapsone, methotrexate, and three TNF- inhibitors. Abatacept was introduced in August 2008 in combination with dapsone (100 mg/day) and methotrexate (15 mg/week). A complete response was obtained within four months (4). CS (initially, 40 mg/day of prednisone) were tapered and stopped within four months. In April 2011, RP signs reappeared with persistent moderate activity. Abatacept was replaced with certolizumab, which had no effect. Abatacept was then reintroduced three months later, leading again to a complete response. No attempt to space out the infusions has been made until now. One serious adverse event occurred: skin cellulitis in mid-2010, cured with oral antibiotics. The second patient was a 62 year-old woman who had not been improved with adalimumab, infliximab and anakinra. She has been exposed to abatacept during 12 months leading to a partial response. CS could be tapered from 60 mg/d to 10 mg/d. No ADR occurred. The drug was then switched to tocilizumab. The third patient was a 39 year-old man who had RP associated with chronic discoid lupus erythematosus. Methotrexate was not efficient. Abatacept was stopped after three months because of insufficient response. CS could not be tapered (12.5 mg/d). No ADR occurred.

  As a result, our experience suggests also moderate to important efficacy of abatacept on ENT chondritis and arthritis. CS-sparing was noteworthy in 2/3 patients and the drug was well-tolerated, even when exposure lasted 1 to 5 years. Patients did not experienced internal organ flare as reported by Peng and Rodriguez, but contrarily to their patients: 1) none of ours had a previous history of such internal organ involvement, 2) we used intravenous, not sub-cutaneous abatacept with the classical loading regimen of 750 mg, three infusion two weeks apart, and 3) our patients were exposed to higher doses of CS at abatacept initiation.

  We totally agree with Peng and Rodriguez regarding the fact that prospective surveys with validated scale assessment (6) should be encouraged to assess efficacy and safety of biologics in RP.

  Funding: no external source of funding. Conflict of interest: none

  References

  1. Peng SL, Rodriguez D. Abatacept in relapsing polychondritis. Ann Rheum Dis 2013;72:1427-9.

  2. Kemta Lekpa F, Kraus VB, Chevalier X. Biologics in relapsing polychondritis: a literature review. Semin Arthritis Rheum 2012;41:712-9.

  3. Leroux G, Costedoat-Chalumeau N, Brihaye B, et al. Treatment of relapsing polychondritis with rituximab: a retrospective study of nine patients. Arthritis Rheum 2009;61:577-82.

  4. Moulis G, Sailler L, Astudillo L, et al. Abatacept for relapsing polychondritis. Rheumatology (Oxford) 2010;49:1019.

  5. Moulis G, Sailler L, Pugnet G, et al. Biologics in relapsing polychondritis: a single center case-series. Arthritis Rheum 2012;64:S816- 7.

  6. Arnaud L, Devilliers H, Peng SL, et al. The Relapsing Polychondritis Disease Activity Index: development of a disease activity score for relapsing polychondritis. Autoimmun Rev 2012;12:204-9.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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