By Dr Isabella Colonna
For November we have selected: Koch MW, Kaur S, Sage K, Kim J, Levesque-Roy M, Cerchiaro G, Yong VW, Cutter GR, Metz LM. Hydroxychloroquine for Primary Progressive Multiple Sclerosis. Ann Neurol. 2021 Sep 30. doi: 10.1002/ana.26239. Epub ahead of print. PMID: 34590328.
Our research paper of the month is an open-label, single-arm, phase II futility trial exploring the safety and the effect of treatment with the antimalarial drug hydroxychloroquine (HCQ) on disability worsening in patients with primary progressive multiple sclerosis (PPMS). Preclinical studies found that hydroxychloroquine reduces the activation of human microglia and protects against experimental neurotoxicity. In line with these works, this research paper aimed to investigate if the treatment with HCQ may decrease or delay the worsening of disability in PPMS patients, by reducing microglial activation and neurodegeneration.
Inclusion criteria were age between 18 and 65 years, diagnosis of PPMS, EDSS score between 4 and 6.5 and a timed 25-foot walk test of ≥5.5 seconds. Patients with enhancing lesions on MRI, renal or hepatic impairment, porphyria, retinopathy, as well as individuals treated withantimalarial drugs, amiodarone, dapsone, or digoxin were excluded from the study.
Forty-nine PPMS patients were enrolled in this trial. However, only 35 patients finished the trial and were included in the analysis. All the study participants were advised to take one 200 mg HCQ tablet twice a day. Study visits were performed at screening, baseline, one, six, 12 and 18 months.
The authors considered a primary outcome to be clinically significant worsening on the timed 25-foot walk at 18 months compared to at six months. The treatment with HCQ would be considered successful if fewer than ten of 35 study participants showed clinically significant worsening. Since only eight of 35 participants experienced a significant disability worsening over the follow-up time, this study met its primary end point. The therapy with HCQ was well-tolerated overall, since only 12% of the study participants enrolled in this trial experienced one serious adverse event.
The authors concluded that treatment with HCQ may reduce disability worsening in patients with PPMS. For this reason, HCQ should be further studied in randomised controlled clinical trials.