Low doses of rituximab, an anti-inflammatory medication used off-label to treat multiple sclerosis (MS), are safer and as effective as higher doses at reducing the frequency of relapses and the number of MS lesions, a clinical study shows.
The study findings were presented at MSVirtual2020 by Luciana Midaglia, MD, a neurologist from the Multiple Sclerosis Centre of Catalonia (Cemcat), in Spain, in an oral presentation titled “Rituximab treatment for MS: an observational multicentric dose comparison (abstract #PS01.05).” The 8th joint MS meeting was held online Sept. 11-13.
The medication is approved for the treatment of various types of blood cancer and is currently sold under several brand names, including Rituxan (by Biogen) in the U.S. and MabThera (by Roche) in Europe.
Although rituximab is currently not approved for the treatment of MS, it is frequently used as an off-label treatment in these patients.
Despite having a well-established safety and efficacy profile, a dosing regimen for rituximab in MS patients is yet to be established.
Thus, investigators assessed and compared the safety and efficacy of a low- and a high-dose regimen of rituximab in a group of MS patients who were being followed at two Catalan MS centers, one in Barcelona and the other in Girona.
All participants included in the study received at least one cycle of rituximab in one of the two MS centers until March 2020.
Those being treated in Barcelona received the high-dose regimen, which was comprised of three cycles of intravenous (into-the-vein) rituximab at a dose of 2 grams, followed by 1 gram every six months thereafter. Patients treated in Girona received the low-dose regimen, which consisted of at least one cycle with 2 grams of intravenous rituximab, followed by 500 milligrams every six months afterward.
Lab tests were performed on all participants every six months. Brain MRI scans were conducted at the start of the study and every year thereafter. Blood samples collected three months after the rituximab infusions were used to measure the levels of CD19-positive B-cells and immunoglobulins (antibodies), and to assess safety.
The frequency of MS relapses — assessed by the annual relapse rate (ARR) — were evaluated after one and three years of treatment with rituximab. The proportion of patients with active or contrast-enhancing lesions (CELs) and new T2 lesions were evaluated at the same times.
Changes in disability progression also were assessed, at the participants’ last follow-up visit, through the expanded disability status scale (EDSS) score.
The analyses now reported were based on data from 303 MS patients, including 249 who received the high-dose regimen in Barcelona and 54 who received the low-dose regimen in Girona. No major differences in age, sex, or disease duration were found between participants followed at the two centers.
In both centers, the main reason that had led patients to start treatment with rituximab was disease progression coupled with high inflammatory activity — 45.8% in Barcelona and 79.6% in Girona.
Among those receiving the high-dose regimen of rituximab in Barcelona, the ARR dropped by 87.5% in the first year of treatment (from 0.4 to 0.05), and by 88.3% after three years of treatment (from 0.68 to 0.08).
A similar trend was seen in patients receiving the low-dose regimen in Girona, with ARR dropping by 90.3% (from 0.31 to 0.03) in the first year of treatment, and by 100% after three years of treatment (from 0.29 to 0). This last result, however, was not statistically significant because the number of patients analyzed (seven) was low.
The overall proportion of patients whose EDSS scores either remained stable or improved — meaning these individuals had less disability — over the course of the study were similar in both centers. In Barcelona, 82.7% of participants remained stable or had less disability, as did 72.2% of those in Girona.
The same was true when evaluating only those individuals with progressive forms of MS, specifically 79.4% in Barcelona and 71.4% in Girona.
The proportion of patients with CELs among those receiving the high-dose regimen dropped from 32.4% to 2.7% after one year, and to 0% after three years of treatment. Similarly, in those receiving the low-dose regimen, the proportion of affected participants dropped from 42.6% to 8% after one year, and also to 0% after three years.
A reduction in the proportion of new T2 lesions also was observed in individuals treated in both MS centers, after one and three years of treatment with rituximab.
In addition, the investigators observed a significant reduction in the levels of CD19-positive B-cells following the first rituximab infusions, which were maintained over time in patients treated at both centers. A significant reduction in immunoglobulin levels also was seen in participants receiving the high-dose regimen in the Barcelona center.
However, the incidence of infections during the first year of treatment with rituximab was higher among those receiving the high-dose regimen in Barcelona, compared with those given the low-dose regimen in Girona — 7.2% vs. 3.7%. The same was true in the second and third years of treatment (9.7% vs. 0%).
The most frequent types of infections observed in these patients were urinary tract infections, followed by respiratory infections.
“To conclude, low doses of rituximab seem to offer similar effectiveness with better safety profile than higher doses,” Midaglia said.
She also noted that a Phase 3 trial, called RIDOSE-MS (NCT03979456), is currently assessing the safety and efficacy of two dosing regimens of rituximab — 500 mg every six or 12 months — in patients with relapsing-remitting MS. Recruitment is ongoing at several sites in Sweden. More information can be found here.
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