#ECTRIMS2021 — Rituximab as First RRMS Therapy Outperforms Others

Editor’s note: The Multiple Sclerosis News Today team is providing in-depth coverage of the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Oct. 13–15. Go here to see the latest stories from the conference.

People with relapsing-remitting multiple sclerosis (RRMS) who are first treated with rituximab are less likely to have disease relapses and brain lesions as compared with patients on other therapies, according to new data from the COMBAT-MS clinical trial.

“Direct comparisons across multiple disease-modifying therapies (DMTs) for [RRMS] are valuable in clinical decision making. … In treatment-naïve patients, [rituximab] was associated with the lowest risk of relapses and MRI lesions, and by far the lowest probability of switching to a second therapy,” researchers wrote in a poster on the trial, presented at the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“These findings underscore the importance of tracking long-term outcomes from first DMT start,” the researchers wrote.

The trial results were discussed at ECTRIMS 2021, in a presentation titled “Effectiveness of initial MS treatments in the COMBAT-MS trial: injectables, dimethyl fumarate, natalizumab and rituximab.”

ECTRIMS is being held online Oct. 13-15.

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COMBAT-MS (NCT03193866) is an observational study comparing the efficacy of different therapies for MS among people with RRMS starting treatment for the first time — patients called treatment-naïve. In the presentation, Peter Alping, a PhD student at the Karolinska Institutet in Sweden, shared data on patients who started therapy between 2011 and 2020.

“Our objective was to compare the effectiveness of the most common initial MS therapies in Sweden,” Alping said.

Among the nearly 2,000 patients in COMBAT-MS, 858 were treated with injectables — a class of MS therapy that includes interferon products as well as glatiramer acetate — while 339 were treated with Tecfidera (dimethyl fumarate), and 269 with Tysabri (natalizumab).

The remaining 472 patients were treated with rituximab, an anti-CD20 therapy that works by killing immune cells called B-cells. Unlike the other therapies in the trial, rituximab is not widely approved to treat MS, though it is commonly used off-label.

Notably, rituximab works very similarly to other anti-CD20 therapies, including the approved MS treatments Ocrevus (ocrelizumab) and Kesimpta (ofatumumab), which were not included in COMBAT-MS.

There were some noted demographic differences among the treatment groups: at the start of therapy, patients on Tysabri tended to be younger, with a shorter disease duration, but more prior relapses, compared with those on other medications.

Statistical analyses showed that rituximab was associated with the lowest risk of first relapse among all the medicines evaluated in COMBAT-MS.

“The injectables had the highest probability of having a first relapse, followed by [Tecfidera and Tysabri] clustered close together, and rituximab had the lowest probability of a first relapse,” Alping said.

Specifically, patients on injectables were nearly six times more likely to have a first relapse than those on rituximab. Patients on Tecfidera were nearly three times more likely to have a relapse, while those on Tysabri were nearly twice as likely to have a first relapse.

The risk of developing new brain lesions over the first three years also was lowest with rituximab — by more than fourfold compared with injectables or Tecfidera, and by nearly twofold compared with Tysabri.

Compared with patients on rituximab, those on injectables had significantly greater disability progression after three years — though these differences were marginal, with only 0.24 greater scores in their Expanded Disability Status Scale (EDSS) assessments. There were no statistically significant differences in disability progression between Tecfidera, Tysabri, and rituximab.

Given the dramatic differences in relapse risk, Alping said that the lack of difference in disability progression was “somewhat surprising.” It may be that three years was too short a time to measure disability progression, or it could be that relapses and disability “explain different parts of the MS disease,” Alping said.

The results also showed that patients on rituximab were least likely to discontinue treatment: the individuals given Tysabri were more than 16 times as likely to stop treatment, while those on Tecfidera were over 20 times as likely to stop. Meanwhile, patients who started on injectables were more than 32 times as likely to stop treatment.

“Injectables had the highest probability of stopping therapy, followed by [Tecfidera and Tysabri] close together, while rituximab has by far the lowest probability of therapy discontinuation,” Alping said.

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At another presentation at ECTRIMS, researchers will share data from COMBAT-MS to assess the relationship between rituximab treatment and the risk posed by COVID-19. The presentation, “No association between rituximab infusion timing nor cumulative dose and hospitalization for COVID-19: evidence from the nationwide COMBAT-MS Cohort,” will be shared later this week.

Of the 326 MS patients enrolled in COMBAT-MS who developed COVID-19 between March 2021 and April 2021, 172 (52.8%) were treated with rituximab prior to contracting COVID-19. Among them, 26 (15.1%) had disease that was so severe they required hospitalization, although none of them died.

Researchers conducted a battery of statistical tests to look for associations between treatment-associated factors — for example, the timing between the most recent infusion of rituximab, or the lifetime dosage of the medication — and the risk of hospitalization from COVID-19. None of the analyses identified statistically significant associations.

“Among COMBAT-MS participants who contracted COVID-19, there was no significant association between timing of RTX [rituximab] infusion nor cumulative lifetime RTX dose and the odds of hospitalization for COVID-19,” the team concluded in the abstract.