Durable Remission in Patients with Refractory Takayasu’s Arteritis Treated with Infliximab or Etanercept
Eamonn S. Molloy, Carol A. Langford, Tiffany M. Clark, Carmen E. Gota, Leonard H. Calabrese, Gary S. Hoffman
While up to 20% of Takayasu’s arteritis (TAK) patients have a monophasic illness, most have a relapsing/remitting course, typically requiring prolonged treatment with glucocorticoids and additional immunosuppressive agents, such as methotrexate, azathioprine and, in severe cases, cyclophosphamide. More than one-third of patients are unable to achieve adequate disease control on these therapies. As tumor necrosis factor alpha (TNFa) is critical for granuloma homeostasis and granulomatous inflammation is the pathologic hallmark of TAK, TNFa is an attractive therapeutic target in TAK; anti-TNF therapy has been employed in TAK patients with encouraging results.
We sought to assess the efficacy of anti-TNF therapy in patients with TAK refractory to other therapies. Twenty-eight TAK patients were identified as having received anti-TNF therapy; 3 patients were excluded because of insufficient follow-up data. No patient was in remission at the time of initiation of anti-TNF therapy; 13 had not achieved remission at any time since initial diagnosis. Twenty-five patients were treated with anti-TNF therapy for up to 6.5 years. Twenty patients were treated with infliximab (INF) with a mean follow-up of 27 months (range 2-76). Nine patients were treated with etanercept (ETA) with a mean follow-up of 33 months (range 4-78). Four patients received both agents (all initially treated with ETA, later switched to INF). No patients were treated with adalimumab.
Of 25 patients, 22 were female; mean age was 35 years (range 15-63). Patients’ ethnicities were Caucasian, 20, Asian,3, Hispanic,1, and one unknown. Median disease duration was 108 months (range 31-336). All patients were previously treated with prednisone and a mean of 2 additional immunosuppressive agents (range 0-6) including 22 methotrexate, 10 cyclophosphamide, and 12 with a variety of other agents.
Overall, prednisone was discontinued in 15/25 patients (60%) and tapered below 10 mg/day in a further 7/25 (28%). Median prednisone dose before and after anti-TNF therapy was 19 mg (range 5-90) and 0 mg (range 0-30). Nine out of 18 patients were able to taper or discontinue additional immunosuppressive agents used concurrently with the anti-TNF agent. Six patients had definite new changes noted on MR imaging (3 INF, 3 ETA); 5 patients entered remission on higher dose anti-TNF therapy. Three patients who stopped ETA had disease flares within a median of 2 months (range 1-2); 6/7 patients that stopped INF had disease flare at a median interval of 6 months (range 2-12); 1 patient recommenced INF treatment and achieved sustained remission.
Conclusions
In this group of TAK patients refractory to other immunosuppressive therapies, anti-TNF therapy led to complete or partial remission in 79% of patients. Anti-TNF therapy allowed prednisone to be discontinued or tapered in 60% and 28%, respectively. Of those patients taking concurrent immunosuppressive drugs other than prednisone, anti-TNF therapy allowed reduction of the dose of these agents in 50%. These findings provide further support for the rationale for randomized controlled trials of anti-TNF therapy in TAK.
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