Data supporting the off-label use of rituximab in adolescents with pediatric-onset multiple sclerosis (POMS) was presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019.
The session, titled “No Evidence of Disease Activity in the Majority of Pediatric-Onset Multiple Sclerosis Patients Receiving Rituximab,” was presented by Nikita Shukla, MD, from the Texas Children’s Hospital/Baylor College of Medicine, on Feb. 28, as part of ACTRIMS’ Poster Session 1.
According to Shukla, “pediatric MS is so unique” given that patients are at a stage where their brains are still developing.
Regulatory bodies in many countries have approved several treatments for adults with MS. However, there is only a limited approval of therapies to treat adolescents and children with POMS.
In the U.S., no medication had been approved by the Food and Drug Administration (FDA) to treat patients with POMS until May 2018, when the agency approved the use of Gilenya (fingolimod, marketed by Novartis) in children 10 years or older. Also, some disease-modifying treatments (DMTs) prescribed for adults with MS are also prescribed for POMS.
A potential POMS treatment is rituximab, but it is not approved for use in MS by the FDA or the European Medicines Agency (EMA). This therapeutic agent has been studied in small trials of pediatric patients with neuroimmunological diseases, where it was shown to be safe and effective. Rituximab has been used by POMS patients, but there is limited data about clinical outcomes.
Thus, researchers from Texas Children’s Hospital/Baylor College of Medicine investigated the effectiveness of rituximab in POMS patients. The goal was to determine to what degree POMS adolescents taking rituximab could achieve no evidence of disease activity (NEDA-3) — a status defined by no brain lesions on MRI (magnetic resonance imaging) scans, no increase in post-treatment disability, and absence of relapses.
The team retrospectively analyzed medical charts and clinical imaging data from 17 POMS participants (mean age of 18 years, ranging from 13 to 22 years), before and after being treated with rituximab for at least six months.
Researchers looked at how rituximab affected the annualized relapse rate, presence of new brain lesions on MRI at least six months after beginning treatment, and disability severity as measured by the Expanded Disability Status Scale (EDSS).
Four of the 17 POMS patients received rituximab as their first DMT; nine had used other DMTs but experienced disease progression; and the remaining four patients had side effects from using other DMTs.
On average, participants were on rituximab for 21 months. They received two doses of 1,000 mg, separated by 14 days, followed by regular booster doses of 750 mg or 1,000 mg.
Results showed that, after treatment, 16 out of the 17 POMS patients did not have a clinical relapse while on rituximab except for one patient who developed optic neuritis (inflammation of the optic nerve).
On their follow-up MRIs, 14 patients showed no new brain lesions. One patient had one new brain lesion at the six-month follow-up, but after another six months of treatment (12-month follow-up), the patient had no new brain lesions. The POMS patient with optic neuritis showed evidence of inflammation in the affected optic nerve, but did not have brain lesions.
All the patients’ EDSS scores remained stable while on rituximab treatment.
Overall, 82% (14 out of 17 patients) receiving rituximab fulfilled the criteria for NEDA-3, the team noted.
Although the study analyzed a small cohort, and was performed on existing data sets, the researchers believe that the “data supports the use of rituximab in POMS, and suggests high rates of NEDA in this population,” they wrote.
According to the team, future longitudinal studies — examining people in real time and over a period of time — with larger cohorts are needed to better understand the effectiveness of rituximab in treating POMS adolescents and children.