Are monoclonals the only panacea for treatment of aquaporin-4 positive NMOSD? Experience from a low-&middle-income (LMIC) region

• Published in: Clinical neurology and neurosurgery Vol. 239; p. 108212
• Main Authors: Dhamija, Kamakshi, Manjappaiah, Mandara Ganganakudige, Kandavel, Thennarasu, Mahadevan, A., Netravathi, M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2024; Elsevier Limited
• Subjects: Annualized relapse rates; Apheresis; Aquaporin 4; Aquaporins; Azathioprine; Cyclophosphamide; Demyelination; Drug dosages; Immunomodulation; Immunosuppressive agents; Methotrexate; MMF; Patients; Rituximab; Steroid hormones; Steroids; Survival analysis; India; ARR; BAFF; DVT; MS; MMF; Rituximab; CNS; IvIg; AQP4+ve; IQR; UTI; NMOSD; N; Aquaporin-4; Annualized relapse rates; Azathioprine; EDSS
• ISSN: 0303-8467; 1872-6968
• DOI: 10.1016/j.clineuro.2024.108212

A plethora of monoclonals have ushered up for NMOSD treatment. However, their limited availability and cost concerns poses a challenge for usage in developing nations. We compared relapse rates and disabilities among aquaporin-4 positive(AQP4+ve) patients on conventional immunosuppressants and rituximab in a tertiary referral center in southern India. This was a chart review of AQP4+ve patients registered under national demyelination registry maintained at institute. AQP4+ve patients were included if they were on azathioprine, MMF, methotrexate for six months; cyclophosphamide for three months and rituximab for one month. 207 records were screened, 154 fulfilled inclusion criteria. Drugs used were azathioprine (70), MMF (34) and rituximab (33). All three drugs were non-inferior to each other in terms of ARR reduction. Median EDSS at last follow-up was significantly lower for azathioprine(2;IQR:0–5) and rituximab(2;IQR:0.5–5) than MMF(3.5;IQR:2–5.6), however azathioprine was associated with highest switch rate(34.3%) and was the only drug which required change because of intolerance. Failure rate was least for rituximab(27.3%).Patients on azathioprine and MMF required higher mean duration of concurrent steroids(7.8±7.7 and 4.56±2.17 months respectively) when compared to rituximab(2.77±1.38) and had more relapses due to steroid withdrawal. Initial treatment with azathioprine, MMF and rituximab is comparable in terms of ARR reduction. Findings suggest that choice may be guided by adverse event profile of drug, rather than efficacy per se. Concurrent treatment duration with steroids should also guide clinical decision. Switch to second immunomodulation in event of initial failure adds to efficacy benefit, irrespective of the drug chosen. •Azathioprine and mycophenolate mofetil fare at par with rituximab in reducing pre-treatment ARR in AQP4+ve NMOSD patients.•Azathioprine was associated with highest switch rate (34.3%), majorly due to intolerance.•Failure rate was least for rituximab (27.3%).•Relapses owing to steroid withdrawal were least with rituximab.