Off-label rituximab tops other disease-modifying therapies for multiple sclerosis
The off-label use of rituximab in the treatment of multiple sclerosis (MS) confers better outcomes than other disease-modifying therapies (DMTs), according to a Swedish observational study. [JAMA Neurol 2018, doi: 10.1001/jamaneurol.2017.4011]
The analysis included 494 patients with relapsing-remitting MS (RRMS) identified from two Swedish patient databases. These patients received first-line treatment with either rituximab (n=120), injectable DMTs (ie, interferon beta or glatiramer acetate) (n=215), dimethyl fumarate (n=86), fingolimod (n=17), or natalizumab (n=50).
Treatment discontinuation rate, the primary endpoint of the study, was significantly lower in patients receiving rituximab vs injectable DMTs, dimethyl fumarate, fingolimod and natalizumab (5.8 percent vs 80.5, 37.2, 47.1 and 48.0 percent, respectively). The differences remained significant after adjusting for covariates and propensity scores.
The main causes of treatment discontinuation differed between the groups. “The most common cause of treatment discontinuation among patients receiving rituximab was pregnancy [3.3 percent]. One patient discontinued due to disease breakthrough,” the authors wrote. “Among patients treated with injectable DMTs, dimethyl fumarate and fingolimod, disease breakthrough and adverse events were the most common causes of discontinuation [injectable DMTs, 38.1 percent and 27.9 percent, respectively; dimethyl fumarate, 16.3 percent and 14.0 percent, respectively; fingolimod, 23.5 percent and 17.6 percent, respectively]. The main reasons for treatment discontinuation in patients receiving natalizumab were positive John Cunningham virus serology [32 percent], followed by disease breakthrough, adverse events and pregnancy [4 percent each].”
Relapse rates were also lower in patients treated with rituximab vs injectable DMTs and natalizumab, but the difference became statistically insignificant after adjusting for propensity scores. Meanwhile, relapse rates were comparable between rituximab, dimethyl fumarate and fingolimod recipients.
Compared with rituximab, the risk of gadolinium-enhancing lesions was higher with injectable DMTs and dimethyl fumarate, and similar with fingolimod and natalizumab.
Overall, adverse event rates did not differ significantly between the rituximab, fingolimod and natalizumab groups. Mild adverse events were more frequent with injectable DMTs and dimethyl fumarate compared with rituximab.
“Data from real-world populations indicate poor drug survival with traditional first-line options for treatment of RRMS, such as interferon beta and glatiramer acetate, with less than half of patients remaining on therapy after 2 years,” the authors wrote. “Real-world studies on newer treatments are still lacking.”
“In our present study, patients receiving rituximab were older and had a longer delay between diagnosis and start of therapy than those receiving natalizumab. However, after correcting for baseline differences, rituximab still displayed more favourable drug survival rates compared with natalizumab,” they noted.
“The main argument for starting with less effective DMTs concerns safety and price,” the authors pointed out. “Although there is extensive experience with long-term use of rituximab in patients with rheumatoid arthritis, which demonstrated a good tolerability profile, extrapolation to MS should be done with caution owing to the differences in patient populations and prescriptions.”
“The cost of rituximab, prescribed at a single dose of 500 mg or 1,000 mg twice yearly, can be lower than that of even the injectable DMTs,” they added. “However, off-label use of rituximab, which is subject to variable insurance regulations in countries other than Sweden, remains a barrier for its uptake in MS.”