“The sixth in a series of posts to try and help neurologists who treat MS in healthcare environments where they cannot access high-cost innovator DMTs. If you want to know the history of this post please read my post on my visit to South Africa. My position on this has been reinforced by recent trips to South America, Lebanon and India; all regions where personal access to DMTs is largely determined by how wealthy you are. The other five off-label DMTs that I have covered to date are methotrexate, azathioprine, mitoxantrone, cladribine and cyclophosphamide.”
“I wasn’t going to include rituximab in this list as it not off-patent and is a relatively high-cost drug. However, on my visit to India I have found that a cheap biosimilar (Reditux) is available and the rheumatologists, who use this formulation in India to treat rheumatoid arthritis, are apparently impressed with its effectiveness and its ability to deplete peripheral B cells in a similar fashion to the innovator product.”
“I have personally used rituximab in a handful of MSers, who were not eligible for licensed drugs, with impressive results. Please note in the UK it is frowned upon to prescribe off-label products were licensed products exist for a particular indication and it is illegal for the NHS to support widespread off-label prescribing of a particular product when licensed drugs exist for that indication. This has been discussed previously on this blog in relation to the issue concerning the use of Avastin, instead of Lucentis, as a treatment for macular degeneration.”
Castillo-Trivino et al. Rituximab in relapsing and progressive forms of multiple sclerosis: a systematic review. PLoS One. 2013 Jul 2;8(7):e66308. doi: 10.1371/journal.pone.0066308. Print 2013.
BACKGROUND: Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS.
OBJECTIVES: To evaluate the efficacy and safety of rituximab for MS treatment.
DATA COLLECTION: Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies.
MAIN RESULTS: Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events.