Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden - Outlier or predecessor?

Berntsson, Shala Ghaderi; Kristoffersson, Anders; Boström, Inger; Feresiadou, Amalia; Burman, Joachim; Landtblom, Anne‐Marie

doi:10.1111/ane.12963

Cited by 52 publications

(50 citation statements)

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“…Second line treatments include fingolimod and natalizumab 60 . In addition to the recommended first line treatments, Rituximab is often prescribed off label, meaning there is limited information on the long term safety and efficacy of this treatment for MS patients 61 . When and how to make the transition from first line to second line treatment can be difficult, with no internationally recognised guidelines on when the decision should be taken and how it should be implemented 62 .…”

Section: Treatment Of Msmentioning

confidence: 99%

The association between multiple sclerosis and pain medications

Burkill

Montgomery

Kockum

et al. 2018

Pain

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Section: Treatment Of Msmentioning

confidence: 99%

The association between multiple sclerosis and pain medications

Burkill

Montgomery

Kockum

et al. 2018

Pain

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“… 1 Rituximab (RTX), a first-generation anti-CD20 mAb, has also been adopted as an off-label treatment in MS, 2 , 3 and it is currently used as standard of care therapy in some European countries. 4 The standard treatment regimen of anti-CD20 mAbs usually consists of an “induction” phase, followed by regular fixed maintenance reinfusions (usually every 6 months). However, despite being a more practical approach in the daily practice, the fixed doses regimen could represent an overtreatment because B cells could be still depleted before each subsequent retreatment dose, as B cell immune reconstitution after B cell depletion ranges from 27 to 125 weeks with a median of 72 weeks.…”

mentioning

confidence: 99%

Tailoring B cell depletion therapy in MS according to memory B cell monitoring

Novi

Bovis

Fabbri

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveWe wanted to evaluate efficacy on inflammatory parameters of rituximab (RTX)-personalized reinfusion scheme using a memory B cell–based treatment regimen.MethodsThis is a prospective, uncontrolled, open-label study including patients with MS treated with RTX in 2 Italian MS units. All patients were treated with RTX induction, followed by maintenance infusion at the dosage of 375 mg/m2, according to memory B cell repopulation (0.05% of peripheral-blood mononuclear cells [PBMCs] for the first 2 years, 0.1% of PBMC for the third year). MS activity was assessed as clinical or MRI activity.ResultsOne hundred two patients were included in the analysis. Mean follow-up was 2.40 years (range 0.57–7.15 years). The annualized relapse rate (ARR) was 0.67 in the year before RTX start and decreased to 0.01 in the 3 years after RTX initiation (global ARR). The proportion of patient with MS activity (i.e., relapse or MRI activity) was 63.16% in the year before RTX start and decreased to 8.7% (0–6 months), 1.3% (6–12 months), 0% (12–24 months), and 0% (24–36 months). Annualized RTX infusion rates were 1.67 (95% confidence interval [CI]: 1.43–1.94), 0.76 (95% CI: 0.58–0.98), and 0.78 (95% CI: 0.52–1.12) for the first 3 years after RTX initiation, respectively. Patients were reinfused with a mean infusion interval of 367 days (range 181–839 days).ConclusionThe results of this study show that the memory B cell–based RTX reinfusion protocol is able to reduce the mean number of RTX reinfusions with persistent reduction of disease activity.Classification of evidenceThis study provides Class IV evidence that for patients with MS, a memory B cell–based RTX reinfusion protocol can reduce the mean number of RTX reinfusions with persistent reduction of disease activity.

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“…As pointed out in our introduction, there is a rapid increase in the use of RTX for MS in Sweden, not only as an alternative when previous DMT was ineffective, but also as a first‐line therapy. By June 2017, over 50% of all treatment naïve subjects with MS in Sweden received RTX as their first DMT . This growth has recently resulted in the Swedish Ministry of Health and Social Affairs planning a risk‐benefit analysis of off‐label RTX use, underlining the importance of our study.…”

Section: Discussionmentioning

confidence: 99%

“…Sweden stands out with its high use of off‐label rituximab (RTX), representing approximately 40% of all ongoing DMTs in MS care . Furthermore, a Swedish study that included subjects with MS from three tertiary academic hospitals showed that as many as 53.3% of all subjects were given RTX as the primary DMT for MS . The published data extracted from the Swedish MS registry show increased off‐label use of RTX for both relapsing‐remitting MS (RRMS) and progressive disease (PMS).…”

Section: Introductionmentioning

confidence: 99%

Rituximab in multiple sclerosis at general hospital level

2020

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| 491 wileyonlinelibrary.com/journal/ane | INTRODUC TI ONSeveral new disease-modifying therapies (DMTs) have emerged during the last decades for people with multiple sclerosis (MS), which brings both opportunities and challenges to daily praxis. There are multiple issues other than drug efficacy that must be addressed before deciding on treatment modality. Besides disease-related inflammatory aggressiveness and subjects' susceptibility to drug-specific adverse events, subjects' preferences, and cost-benefit aspects also have to be taken into consideration. As a consequence, a gap is developing between the national guidelines authorized by the Swedish Medical Products Agency 1 and real-life treatment selection.Sweden stands out with its high use of off-label rituximab (RTX), representing approximately 40% of all ongoing DMTs in MS care. 2 Furthermore, a Swedish study that included subjects with MS from three tertiary academic hospitals showed that as many as 53.3% of all subjects were given RTX as the primary DMT for MS. 3 The published data extracted from the Swedish MS registry show increased Objectives: The use of rituximab (RTX) in multiple sclerosis (MS) is a rapidly increasing choice of disease-modifying therapy. Efficacy outside specialized university hospital-based care is not yet systematically investigated. Our aim was to evaluate off-label RTX treatment for MS at a general hospital in Sweden. Materials and Methods: Subjects with definite MS with at least one rituximab infusion were eligible for inclusion in this retrospective, observational study. Effect was evaluated by monitoring clinical disability, annual relapse rate, new lesions on MRI, and safety by the incidence and severity of adverse events. Results: Among the 83 included subjects, 15 had clinical worsening of disease during the median 23.5 (1-76) months of follow-up after RTX initiation: 7/66 with relapsing-remitting multiple sclerosis (RRMS) and 8/17 with progressive subtypes (PMS).Cumulative survival without worsening was 86% in RRMS and 30% in PMS. The annual relapse rate before RTX vs follow-up dropped from 0.38 to 0.05 (P < .00001).Subjects with new enhancing lesions on MRI during the first year before RTX initiation vs the year after dropped from 0.94 to 0.024 (P < .00001) and was only seen in RRMS (1.05-0.31, P = .00003). Adverse events were mainly mild. Thirty-six out of 53 non-infusion-related adverse events were infections, of which four were serious, including a case of pneumonia with concomitant late-onset neutropenia. Conclusions:Rituximab was as effective and safe when given at a general hospital outpatient clinic compared with results from previous university hospital-based studies. Vigilance is required concerning severe adverse events. K E Y W O R D Smultiple sclerosis, rituximab, safety management

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Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden - Outlier or predecessor?

Abstract: The share of MS patients in Sweden who are treated with rituximab is very high, and also rapidly increasing. Taken into account the off-label use, cases with adverse medical conditions that could possibly be related to rituximab use should be reported thoroughly.

Cited by 52 publications

References 21 publications

The association between multiple sclerosis and pain medications

The association between multiple sclerosis and pain medications

Tailoring B cell depletion therapy in MS according to memory B cell monitoring

Rituximab in multiple sclerosis at general hospital level

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