Rituximab is a monoclonal antibody currently being investigated as a potential therapy for multiple sclerosis.

Rituximab is an approved treatment for various types of blood cancer, and is marketed under the name Rituxan (in the U.S.) and MabThera (in Europe).

How rituximab works

Rituximab is a monoclonal antibody (a protein designed to target and attach to a specific protein) that interferes with the growth and spread of leukemia and lymphoma cancer cells. It works by targeting thee CD20 antigen, a substance found on the surface of certain immune cells called B-cells. Rituximab binds to the antigen on the cell surface which activates B-cell death. Because B-cells contribute to myelin damage in multiple sclerosis, rituximab may be helpful for treating the disease.

Studies involving rituximab for RRMS

Early studies of rituximab in people with neuromyelitis optica (NCT00501748) tested the drug’s safety. Although preliminary results from a group of eight people with neuromyelitis optica showed that B-cell depletion may enhance neurological recovery from attacks, there is still no published data from this study.

Rituximab has undergone other clinical studies in patients with different types of MS.

A Phase 2 study (NCT00097188) evaluated the safety and effectiveness of rituximab in adults with remitting-relapsing multiple sclerosis  (RRMS). Participants showed reduced numbers of new brain lesions and a 50% reduction in relapses.

A Phase 2/3 study (NCT00087529) evaluated the safety and effectiveness of rituximab in adults with primary progressive multiple sclerosis (PPMS). This trial compared rituximab to a placebo. Though rituximab did not prove effective, it was safe for people with PPMS.

A study (NCT01212094) involving people with secondary progressive multiple sclerosis (SPMS) was terminated because cerebrospinal fluid biomarkers failed to reach the criteria for continuation. This trial included 27 people with SPMS who received rituximab injections intrathecally (into the spine).

There are no Phase 3 trials currently planned for rituximab in MS, though the drug is licensed for other diseases and is currently used off-label for MS. Off-label use of rituximab for MS has received positive response — the observed annualized relapse rate and MRI disease activity were low during rituximab treatment, providing evidence that it is a safe and effective treatment for MS for up to 2 years. The compiled data for the outcome of off-label rituximab use in MS patients has been analysed and published in the scientific journal, Neurology.

Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

 

Rituximab Linked to Greater Risk of Infections in MS Patients in Real-world Swedish Study

Newer disease-modifying treatments for multiple sclerosis (MS) are effective but also known to carry a greater risk of infections in a patient group already more likely to be troubled by infections — and this higher risk is particularly evident in treatment with rituximab, a DMT often used off-label in Sweden, a nationwide study into its […]

#ECTRIMS2019 – Ofatumumab Part of ‘Magnificent Success Story’ for MS, ASCLEPIOS Trial Investigator Says

Ofatumumab, an investigational B-cell therapy being developed by Novartis, demonstrated encouraging results in lowering relapse rates and active brain lesions in people with relapsing multiple sclerosis (MS) enrolled in the ASCLEPIOS trials. For Stephen L. Hauser, MD, an investigator in the ASCLEPIOS trials, these results represent a decades-long journey to better understand MS and what he […]

MS News that Caught My Eye Last Week: Rituximab vs. Ocrevus

In this week’s column, I’ve changed the format a little to focus on one subject: rituximab. This is an approved cancer medication that some U.S. neurologists use as an off-label treatment for multiple sclerosis (MS). Rituximab is similar to Ocrevus (ocrelizumab). When the latter disease-modifying therapy (DMT) became available in the U.S., some people with […]

#ECTRIMS2019 – Is Rituximab a Reasonable Option for MS Patients? No, Researcher Says

Editor’s note: This is the third story in a three-part report examining the question, “Is rituximab a reasonable alternative treatment for MS?”, which was a topic discussed at this year’s Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Here, we take an in-depth look at the arguments presented against rituximab […]

#ECTRIMS2019 – Is Rituximab a Reasonable Option for MS Patients?

Editor’s note: This is the first story in a three-part report examining the question, “Is rituximab a reasonable alternative treatment for MS?”, which was a topic discussed at this year’s Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Here, we provide a synopsis of the argument. *** More than two […]

MS News that Caught My Eye Last Week: Rituximab Helps Reverse Boy’s MS, Top Secondary DMTs in Europe, Tricking Remyelination, Early MS Treatment Strategies

Rituximab Leads to ‘Dramatic’ Recovery in Boy with Aggressive RRMS, Case Study Reports I dislike using adjectives such as “dramatic” when describing treatment results. I think they frequently blow things out of proportion. However, after reading about how this young boy in Greece responded to Rituximab as a “rescue therapy” I think that “dramatic” may […]

Rituximab Leads to ‘Dramatic’ Recovery in Boy with Aggressive RRMS, Case Study Reports

Treatment with rituximab — sold as Rituxan in the U.S. by Roche and Biogen, and as MabThera by Roche in Europe — reversed disease course in a “dramatic fashion,” leading to complete remission in a 12-year-old boy with aggressive relapse-remitting multiple sclerosis (RRMS), a case report states.

The report, “Rituximab as Rescue Therapy for Aggressive Pediatric Multiple Sclerosis,” was published in the journal Case Reports in Pediatrics.

Almost 1 in 10 MS patients has a history of disease onset as a child. But while numerous therapy options exist for adults with MS, treatments available to children are limited.

One emerging potential therapy is rituximab, approved to treat various types of blood cancer and used off-label in some people with MS. It is a monoclonal antibody that targets CD20, a protein found on immune B-cells, triggering their death. Because B-cells can contribute to inflammation and myelin damage in MS, rituximab may be helpful in treating the disease.

A number of studies examining rituximab’s use in adults with RRMS have reported promising results.

Researchers in Greece described the case of a 12-year-old boy with particularly aggressive RRMS, who was unable to attain remission before being treated with rituximab.

The child, previously healthy, was admitted to P & A Kyriakous Children’s Hospital in Athens with complaints of headache, ataxia (lack of voluntary movement coordination), and paresthesias (burning or prickling sensations).

Magnetic resonance imaging (MRI) scans depicted numerous active lesions in the brain and one in the spinal cord. Based on these finding, a provisory diagnosis of clinically isolated syndrome (CIS) — a first MS manifestation — was made. He was prescribed gamma globulin and pulses of corticosteroids, which were subsequently tapered.

Although his condition quickly improved and MRI lesions partially resolved, the boy relapsed two months later and symptoms returned. Scans showed a worsening in brain damage and new lesions.

Treatment with corticosteroids and cyclophosphamide were of little help, and he kept having relapses (every four to six weeks) with evidence of clinical and radiological deterioration.

“On every occasion, his condition would partially improve after corticosteroid pulse therapy, only for a following relapse to occur while tapering the oral steroids,” the scientists reported.

Eight months after the start of therapy, his condition had declined significantly. He was unable to walk alone for more than 50 meters (about 164 feet), and had vision problems (double vision and repetitive, uncontrolled eye movements), slurred speech, and difficulties with movement affecting his left side.

His disability degree, as measured by an EDSS score, was 6.5 — more than midway along this scale. Numerous old and new lesions across the brain and cervical spinal cord were evident.

Doctors were particularly concerned with a lesion in the brainstem (the posterior part of the brain that connects it with the spinal cord) that was pressing against the pyramidal tracts. These are bunches of nerve fibers responsible for transmitting information from the cerebral cortex to the spinal cord and brainstem, and are fundamental to controlling movement.

As the boy’s life was at risk, doctors decided on a “rescue therapy” with rituximab, given as weekly infusions into the vein for one month. Soon after the second infusion, the boy’s symptoms started improving. By the end of the treatment (a total of four doses) “his condition had improved dramatically,” the researchers wrote; he was “troubled only by a mild tremor and nystagmus [repetitive eye movement.”

No new lesions were found on MRI scans, and the existing ones were either fewer in number or significantly smaller. None of the evident lesions had MRI contrast enhancement, indicating repair of the myelin coating around nerve fibers.

Given the lack of published information about rituximab’s use in children with MS, treatment continued with conventional immunomodulating agents, with a cyclophosphamide course followed by mycophenolate mofetil (sold as CellCept by Genentech).

Three years after his diagnosis and two years after being treated with rituximab, the teenager remains free of symptoms, with an EDSS score of zero. “He did not experience any further relapses, and subsequent brain and spine MRIs showed further improvement,” the team reported.

Researchers believe that B-cell-related inflammation, which was uncontrolled in this child since disease onset, “is probably the reason why rituximab had such an impressive effect in our patient’s condition,” they wrote.

B-cell-depleting therapies like rituximab or Ocrevus (ocrelizumab; by Genentech), for this reason, could be “a promising therapeutic approach for pediatric MS, especially at the early stages of the disease, when B-cell-related phenomena are pronounced,” they concluded, and warrant clinical trials to further examine their effectiveness in young patients.

“Newer anti-CD20 [B-cell] monoclonal antibodies, such as ocrelizumab, feature an enhanced antibody-dependent cellular toxicity when compared to rituximab, with a proven efficacy in adult MS patients,” the researchers added.

Autoimmune Complications Associated with Lemtrada Solved Using Anti-CD20 Therapies, Case Studies Suggest

Relapsing-remitting multiple sclerosis (RRMS) patients treated with Lemtrada (alemtuzumab) may develop additional (secondary) autoimmune reactions. Anti-CD20 therapies, including rituximab or Ocrevus (ocrelizumab), are a potential treatment for Lemtrada-associated autoimmune complications in patients who fail to respond to other conventional immunotherapies, according to a case report about two women in Australia. The study, “B cell depletion therapy resulting in […]

#AANAM — Use of Highly Effective Treatments for RRMS Increasing but Still Limited, Study Says

Although the use of highly effective disease-modifying treatments (HETs) in patients with relapsing-remitting multiple sclerosis (RRMS) has increased, they still represent a minority among the treatment strategies used, according to a study. The study, “Trends in the use of Highly Effective Disease Modifying Treatments in Multiple Sclerosis over 12 years across 10 Sites,” was presented […]