Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in [ME/CFS], 2024, Rekeland, Fluge, Mella et al.

Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Ingrid G. Rekeland; Kari Sørland; Lisbeth Lykke Neteland; Alexander Fosså; Kine Alme; Kristin Risa; Olav Dahl; Karl J. Tronstad; Olav Mella; Øystein Fluge

OBJECTIVES
In this six-year follow-up study, we used patient-reported outcome measures (PROMs) to compare values at baseline, at 18 months, and at six-year follow up from the CycloME and the RituxME trials.

METHODS
Based on the hypothesis that ME/CFS in a subgroup of patients is a variant of an autoimmune disease, we performed two clinical trials between 2014 and 2017. The RituxME trial was a randomized, double-blind and placebo-controlled phase III trial of 151 patients, assessing the B-cell depleting antibody rituximab. The CycloME trial was an open-label phase II trial of 40 patients using intravenous cyclophosphamide. Here we report six-year follow-up from both trials, using the Short Form 36 Physical Function (SF-36 PF) and DePaul short form (DSQ-SF) questionnaires.

RESULTS
Of the patients available after six years, 75.7% of RituxME and 94.4% of CycloME patients participated. In the RituxME rituximab group, the mean SF-36 PF scores were 32.9 at baseline, 42.4 at 18 months and 45.5 at six years. In the placebo group, the mean SF-36 PF scores were 32.3 at baseline, 45.5 at 18 months and 43.1 at six years. In the CycloME trial, mean SF-36 PF increased from 35.4 at baseline to 54.4 at 18 months, and 56.7 at six years. At six-year follow-up, 44.1% of cyclophosphamide-, 27.6% of rituximab- and 20.4% of placebo-treated patients had an SF-36 PF ≥ 70, and further, 17.6%, 8.6% and 7.4% of the corresponding patient groups had an SF-36 PF ≥ 90, which is within normal range. In terms of worsening at six years, 5.9% of cyclophosphamide-treated, 10.3% of rituximab-, and 14.8% of placebo-treated patients had a drop in SF-36 PF of 20 points or more from baseline. There were no serious unexpected adverse reactions.

CONCLUSIONS
After six years, 44.1% of the cyclophosphamide group scored an SF-36 PF of at least 70, and 17.6% of at least 90, suggesting that cyclophosphamide in a subgroup may modulate the disease course in a beneficial way. However, cyclophosphamide carries toxicity concerns and should not be used for ME/CFS patients outside clinical trials. Rather, these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.

Link | PDF (PLOS ONE) [Open Access]

 

The baseline IGG data by responder data for cyclophosphamide which was included in the Rekeland dissertation was not included here. Also the HLA risk alleles data are not discussed at all here.

 

Just some speculation: It makes sense to publish this broader look at the cohorts first. Publishing data with strong emphasis on responders first would risk creating too much hype for a very potent/harmful drug. Shouldn’t be this way - data is is data, but with the politisation of the field neutrality becomes much more of an exercise in communication. If they save more details on responders for a second paper , I think it would be the best way to preserve credibility across the board.

 

Any idea what they might be referring to here? Like do they have drugs in mind or is it just, this seems to help so lets see how its helping and and maybe that will point us to better drugs.

And if cyclo is beneficial for a subset of us, surely there is a point of severity where the toxicity is a risk worth taking? Like very severe? Or maybe even severe like myself. Obviously for someone mild maybe it's better to wait for better drugs. Like obviously it should be studied more beforehand to identify who will respond but still.

 

Possibly/probably Daratumumab.

https://en.wikipedia.org/wiki/Daratumumab

But I agree with you that it is much more helpful to specifically call out specific treatments by name, even if there is some speculation involved.