A proof of concept study of Infliximab for the treatment of HTLV-1-associated myelopathy

Background

Disease modifying treatment options for patients with HAM are limited. Most studies have included all patients regardless of duration, disability or disease activity. The Medical Research Council UK funded a series of proof of concept studies for patients with early (50% deterioration during preceding 3 months). The results of the first study of ciclosporin have been published. The second study, of the anti-TNF monoclonal antibody Infliximab, is presented.

Study design

Open-label, clinical endpoint study of Infliximab 3mg/kg infused intravenously at weeks 0, 2 and 8 and then every 8 weeks until and including week 40 of the study. Primary endpoints were time to and incidence of clinical failure.

Results

The study was terminated early for futility. Three patients were recruited to and completed the study. Patient #1 developed a rash and headache after the 2nd infusion. This was considered to be immune complex mediated. Patient #2 experienced hypersensitivity reaction with profound hypotension during the 4th infusion (week 16). In both cases treatment was discontinued. Patient #3 completed all 7 infusions without adverse effect. Reduced spasticity was observed in all 3 patients during on-treatment period. Patient #1 was unable to stand throughout the study. 10m timed walk improved in Patient #2 but deteriorated in #3. No trend was observed in pain scores, β2M or HTLV-1 viral load in blood and CSF.

Conclusion

High severe adverse event rate with Infliximab therapy was observed. Future studies should co-administer with methotrexate as per the treatment of rheumatoid arthritis.