Low-dose methotrexate in sickle-cell disease: a pilot study with rationale borrowed from rheumatoid arthritis


                  <p>Inflammation is a major feature of sickle cell disease (SCD). Low-dose methotrexate (MTX) has long been used in chronic inflammatory diseases. This pilot study examined the MTX effect on acute vaso-occlusive pain crises (VOC) in SCD patients.</p> 

                  <p>Fourteen adults on hydroxyurea with severe and refractory VOC received one intramuscular injection of 10 mg of MTX per week for 12 weeks. A single weekly dose of 5 mg of leucovorin was administered orally 48 h after each MTX injection. The primary outcome was reduction in number/intensity of acute pain episodes. The secondary outcomes were improvement of quality of life (QOL) and reduction of the inflammatory status.</p> 

                  <p>MTX did not significantly change the median VOC frequency (12 before vs 10.5 during treatment, <em>P</em> = 0.6240) or the median McGill pain index (45 at week 0 vs 39.5 at week 12, <em>P</em> = 0.9311). However, there was a decrease of ≥50% in chronic pain resulting from avascular osteonecrosis (AVN) in 5 out of 7 patients with radiologic evidence of AVN, with the perception of longer pain-free periods. There was a 44.4% median gain in physical function in the SF-36 QOL questionnaire (<em>P</em> = 0.0198). MTX treatment up-regulated two C-X-C motif chemokines (CXCL), CXCL10 (<em>P</em> = 0.0463) and CXCL12 (<em>P</em> &lt; 0.0001), without significant effect on 14 additional plasma inflammatory markers. Adverse events: One individual had fever of unknown origin. Respiratory tract infections were recorded in five patients. Among the latter, one also had dengue fever and another had a central venous line infection and died of pneumonia and septic shock. Three patients with previous history of hydroxyurea-induced hematological toxicity developed low blood platelet counts while receiving simultaneously MTX and hydroxyurea.</p> 

                  <p>Although MTX did not reduce acute VOC frequency/intensity, it decreased chronic pain and led to QOL improvement.</p> 
                             <em>Trial registration</em>  
                             <a href="http://ift.tt/1kUfn4Q">http://ift.tt/1kUfn4Q</a> and <a href="http://ift.tt/1Mmy6an">http://ift.tt/1Mmy6an</a>, RBR-2s9xvn, 19 December 2016, retrospectively registered</p> 
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