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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 proinflammatory cytokines blockers as tumor necrosis factor (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 ear, nose and throat (ENT) chondritis and on swollen and tender joint counts. Nevertheless, two patients developed severe central nervous system and pulmonary involvement at weeks 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 patients with RP 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 day 1, day 15 and day 30, 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 4 months.4 CS (initially, 40 mg/day of prednisone) were tapered and stopped within 4 months. In April 2011, RP signs reappeared with persistent moderate activity. Abatacept was replaced with certolizumab, which had no effect. Abatacept was then reintroduced 3 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 did not improve with adalimumab, infliximab and anakinra. She had been exposed then to abatacept for 12 months leading to a partial response. CS could be tapered from 60 to 10 mg/day. 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 3 months because of insufficient response. CS could not be tapered (12.5 mg/day). 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 1–5 years. Patients did not experience 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 subcutaneous abatacept with the classical loading regimen of 750 mg, three infusions 2 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 assessment6 should be encouraged to assess efficacy and safety of biologics in RP.
Competing interests None.
Provenance and peer review Not commissioned; internally peer reviewed.
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