Therapeutic Options in Anti–Jo-1 Antisynthetase Syndrome With Interstitial Lung Disease: Comment on the Article by Marie et al


We read with interest the article by Marie and coworkers published recently in Arthritis Care & Research ([1]). The article evaluated and clarified several unmet points regarding anti–Jo-1 antisynthetase syndrome with interstitial lung disease (ILD), in particular the role of high-dose steroids, cyclophosphamide (CYC), mycophenolate mofetil, and azathioprine in the treatment of patients with this condition. However, we believe that other possible useful therapeutic options should be mentioned.

Good results have been reported in small pilot studies of rituximab ([2, 3]), tacrolimus ([4]), and cyclosporine (CYS) ([5]). In particular, rituximab in a retrospective study appeared to stabilize and/or improve ILD in 7 of 11 patients (10 anti–Jo-1 positive and 9 refractory to other immunosuppressants) during the first 6 months after treatment ([2]). In addition, Marie et al recently reported the 1-year effectiveness of rituximab in 7 anti–Jo-1 patients with refractory ILD ([3]); again, rituximab significantly improved forced vital capacity (FVC), improved diffusing capacity for carbon monoxide (DLCO), and reduced high-resolution computed tomography extension of ILD. Wilkes et al ([4]) examined tacrolimus in 12 anti–Jo-1 patients with ILD for an average of 51.2 months, with a significant improvement of FVC and DLCO; of these patients, 5 were previously not responsive to azathioprine and 2 were not responsive to CYC. Koreeda et al found that CYS, another calcineurin inhibitor like tacrolimus, led to ILD improvement in 4 of the 5 anti–Jo-1 treated patients they examined ([5]).

We recently described our experience on the long-term effectiveness of CYS in 17 anti–Jo-1–positive patients with ILD ([6]); all patients failed prednisone treatment and were subsequently started on CYS (3 mg/kg/day). The median followup time for CYS was 96 months (interquartile range 57–120 months). In all cases, treatment led to improvement of FVC, DLCO, and alveolitis, independent of chest high-resolution computed tomography pattern (e.g., nonspecific interstitial pneumonia or usual interstitial pneumonia). Taken together, these data confirm that in anti–Jo-1–positive antisynthetase syndrome, several therapeutic options should be taken into account in order to reduce the burden of the disease. By considering the peculiarity of ILD in antisynthetase syndrome, as suggested by a proteomic study ([7]) and the wide range of clinical manifestations described in this setting ([8, 9]), further controlled studies are warranted to establish the optimal treatment in these patients.