Lower doses of rituximab than commonly administered to patients with neuromyelitis optica spectrum disorder appear to be still effective at lowering relapse rate and reducing disability, an Australian trial has confirmed.
The researchers, led by Brisbane neurologists, said there was a lack of evidence on optimal dosing for rituximab, despite the B-cell suppression therapy being commonly used in the first line for neuromyelitis optica spectrum disorder (NMOSD) – a relapsing autoimmune inflammatory astrocytopathy.
They reviewed the medical records of 37 patients with NMOSD who received rituximab as two 500mg infusions two weeks apart followed by single 500mg doses, which was lower than the most commonly published regimens.
Patients came from two major hospitals and were followed for an average of 4.5 years. Of them, 27 were positive for AQP4 antibodies (96% female, mean age at first rituximab infusion 45) and 10 were negative (60% female, mean age 35).
Findings published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical [link here] showed that the relapse rate in people with NMOSD after treatment with rituximab was significantly lower than the rate before treatment (annualised relapse rates [ARR] post versus pre treatment: 0.136 versus 0.366).
Interestingly, the reduction was significant in participants who were seropositive for AQP4, but not for those who were seronegative, said the researchers, which included Associate Professor Stefan Blum from Princess Alexandra Hospital.
This might be due to the small cohort of seronegative patients and a greater degree of disease heterogeneity in the cohort, the researchers added.
The ARR for the seropositive group was 0.375 and 0.097 pre and post rituximab.
Rituximab was also associated with a significant improvement in disability as measured by Modified Rankin scores, with a median mRS of 2 (IQR: 1–3) prior to rituximab and 1 (IQR: 1–2) at the time of last follow-up for the total cohort.
The researchers said this was “an encouraging finding” in light of the long follow-up durations, where aging and medical comorbidities could begin to impair function.
A favourable safety profile was also identified, with a relatively small proportion of patients developing hypogammaglobulinaemia and a third developing infections during follow-up after receiving rituximab, most of which were mild. Urinary tract infection in the setting of a urinary catheter was particularly common.
“Patients with NMOSD require lifelong preventive treatment given the potential for devastating relapses and as such, an aim of rituximab therapy should be to administer effective doses, but avoid overtreating which may increase adverse effects, including hypogammaglobulinaemia and infections,” the authors said.
“The results of this study suggest that rituximab may be an effective therapy for NMOSD at lower doses than initially reported.”
The researchers said there should be further investigation into the most effective and safe dose of rituximab for treating NMOSD by comparing more dosing regimens. However, they concluded that for the time being effective treatment with a lower dose can enhance safety and reduce side effects, and ultimately improve outcomes for patients with NMOSD.