Corticosteroid refractory transverse myelitis

Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1- 10 ). The overall response rate was % (44/54) in SR-aGVHD including 25 complete responses (%), while for SR-cGVHD the ORR was % (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was % (3/44) and % (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (-%, 95% confidence interval (CI)) and % (-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, % and 18/54, %) and SR-cGVHD (7/41, % and 6/41, %) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

Corticosteroids are considered a drug of choice for the treatment of patients with moderately to severely active Crohn's disease (CD), an inflammatory bowel disease characterized by chronic recurrent flares of disease activity. However, among patients receiving corticosteroid therapy for induction of remission, 20% have corticosteroid-refractory disease and 36% of those with an initial response develop corticosteroid dependency within 1 year. Chronic corticosteroid exposure in patients who are corticosteroid dependent increases the risk for serious drug-related adverse effects. Withdrawal or reduction of corticosteroid therapy without exacerbation of symptoms is therefore recognized as an important goal of treatment. Therapies that have been shown to facilitate “steroid sparing” include the immunomodulators azathioprine/6-mercaptopurine and methotrexate and the antitumor necrosis factor-α monoclonal antibody infliximab. In corticosteroid-dependent patients, budesonide may be substituted for conventional corticosteroid therapy without loss of response and with less risk for toxicity, but its long-term efficacy requires further evaluation. A preliminary controlled study suggests that the investigational anti-TNF monoclonal antibody CDP-571 may also be clinically beneficial as a corticosteroid-sparing agent. This review summarizes the clinical evidence that supports consideration of these agents as alternatives in patients with CD who are dependent on, refractory to, or intolerant of conventional corticosteroid therapy.

Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was % (44/54) in SR-aGVHD including 25 complete responses (%), while for SR-cGVHD the ORR was % (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was % (3/44) and % (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (-%, 95% confidence interval (CI)) and % (-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, % and 18/54, %) and SR-cGVHD (7/41, % and 6/41, %) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

Corticosteroid refractory transverse myelitis

corticosteroid refractory transverse myelitis

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corticosteroid refractory transverse myelitiscorticosteroid refractory transverse myelitiscorticosteroid refractory transverse myelitiscorticosteroid refractory transverse myelitiscorticosteroid refractory transverse myelitis

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