Rituximab More Effective Than Gilenya, Tecfidera, and Comparable to Tysabri, Study Finds

Rituximab is more effective and leads to fewer treatment discontinuations in people with multiple sclerosis (MS) than Gilenya (fingolimod) and Tecfidera (dimethyl fumarate), according to real-world data based on two years of therapy.

Rituximab’s effectiveness appeared to be comparable to that of Tysabri (natalizumab), but with fewer treatment discontinuations.

These findings suggest that rituximab may be a better therapeutic option to suppress disease activity and maintain long-term treatment among these patients.

The study, “Rituximab versus natalizumab, fingolimod, and dimethyl fumarate in multiple sclerosis treatment,” was published in the journal Annals of Clinical and Translational Neurology.

Rituximab is an antibody-based therapy that works by killing B-cells, a type of immune cell that drives inflammation in MS and other conditions. It is marketed as Rituxan (by Biogen) in the U.S and as MabThera (by Roche) in Europe, with other brand names used elsewhere in the world.

While not approved for MS itself, rituximab is used off-label as an MS treatment. Data from MS clinical trials and real-world studies suggest that the therapy safely and effectively lessens lesions and relapse rates in both relapsing-remitting MS (RRMS) patients and those with progressive forms of the disease.

However, few studies have compared the effectiveness of rituximab with that of other highly effective, immunomodulatory MS therapies, such as Novartis’ Gilenya and Biogen’s Tysabri and Tecfidera. Furthermore, most of these studies were conducted in Swedish RRMS patients and involved a limited number of participants, preventing accurate conclusions and their generalization.

So, researchers at the University of Colorado’s Rocky Mountain MS Center compared rituximab’s effectiveness and discontinuation patterns with those of Gilenya, Tysabri, and Tecfidera in more than 1,200 MS patients followed at their center.

The team retrospectively analyzed data from people diagnosed with any type of MS and treated with rituximab (182 patients), Gilenya (271 patients), Tysabri (451 patients), and Tecfidera (342 patients) up to two years or until therapy discontinuation.

After several adjustments, the team was able to create well-balanced patient groups for comparison. Therapy effectiveness was evaluated through a composite measure comprising the occurrence of clinical relapse and the presence of active and/or new brain lesions.

Treatment discontinuation was considered when a patient was no longer on the therapy after two years, or initiated any other MS disease-modifying therapy during that time. The main reason for treatment discontinuation also was assessed.

Results showed that rituximab treatment led to significantly greater effectiveness outcomes and fewer discontinuations by twofold to threefold, compared with Gilenya and Tecfidera.

Gilenya and Tecfidera discontinuations appeared to be driven by the occurrence of adverse events (side effects), mainly gastrointestinal problems, limiting the achievement of long‐term treatment. Few patients on rituximab stopped treatment due to adverse events, with infections (2.7%) being the most common reported.

While the chances of showing disease activity appeared to be comparable between patients treated with rituximab and those with Tysabri, rituximab’s effectiveness was significantly superior when accounting for time to therapeutic effect (data from six months onward).

Nevertheless, the team hypothesized that this difference likely was driven by immune reactions against Tysabri and missed or delayed Tysabri doses — Tysabri is administered monthly, while rituximab is given twice a year — rather than differences in efficacy.

Compared with Tysabri, rituximab was associated with fewer discontinuations when excluding those due to insurance issues. Such issues were identified as the main cause of rituximab discontinuations in these patients because off-label use poses a challenge for coverage in the U.S., researchers noted.

The main driver of Tysabri discontinuations was the presence of the John Cunningham virus. This virus can trigger a rare and often fatal disease called progressive multifocal leukoencephalopathy that sometimes occurs in Tysabri-treated patients due to low immune cell numbers in the brain.

Few patients discontinued Tysabri due to adverse events, with the most common being flushing, rashes, or hot flashes (3.1%).

Notably, similar results were found when analyzing data from RRMS patients only, and the overall findings were generally consistent with those reported in previous studies.

“Results suggest superiority of [rituximab] in reducing disease activity and maintaining long‐term treatment in a real‐world MS cohort,” the researchers wrote, adding that “further long‐term studies are needed to investigate rare serious adverse events and their risk factors for patients treated with these highly effective therapies.”

Of note, three of the six authors of the study have consulted or received funding from Biogen, Novartis, and/or Genentech.