Two Cases of Pediatric AQP4-Antibody Positive Neuromyelitis Optica Spectrum Disorder Successfully Treated with Tocilizumab

Abstract

B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.

Pediatric NMOSD: A Review and Position Statement on Approach to Work-Up and Diagnosis

“…Safety concerns described with tocilizumab treatment in adult patients with rheumatoid arthritis include the risk of cardiovascular disease and increase in cholesterol levels ( 101 ). Published experience of tocilizumab use in pediatric patients includes a 14-year-old boy suffering from NMOSD and Sjogren's syndrome and two female adolescents with AQP4 IgG positive NMOSD who relapsed during rituximab treatment ( 38 , 110 ). In all of them, tocilizumab led to clinical stabilization without an increased frequency of infections, or the adverse events observed in adults.…”

Anti-IL-6 Therapies for Neuromyelitis Optica Spectrum Disorders: A Systematic Review of Safety and Efficacy

“…Of the 12 case reports of tocilizumab in NMOSD, 11 are documenting treatment outcomes in AQP4+ patients [ 69 - 77 , 79 , 80 ], and 1 in seronegative patient [ 78 ]. Except for 2 case reports of tocilizumab therapy in pediatric patients [ 73 , 75 ], all other studies document treatment outcomes in adults. The TANGO study is a randomized comparative trial of tocilizumab versus azathioprine in highly active NMOSD, where the primary endpoint is time to first relapse following the study initiation.…”

“…Six studies report a significant improvement in the neurological status during tocilizumab treatment, as measured by the expanded disability status scale (EDSS) [ 69 , 71 , 74 , 83 , 86 , 88 ], two report mild improvement [ 72 , 80 ], in 2 the EDSS remained unchanged [ 81 , 82 ], and in 7 data on EDSS before and after treatment is not available [ 72 , 73 , 75 - 79 ]. Lotan et al .…”

“…No radiological disease activity during tocilizumab treatment, as measured by new or enhancing MRI lesions, is reported in 9 studies [ 69 , 70 , 73 , 76 - 78 , 81 , 82 , 86 , 90 ], while three others report improvement in lesion volume in the brain [ 72 ] and the spinal cord [ 71 , 91 ]. Ringelstein et al .…”

“…Decreased AQP4 Ab titers were found in 6 studies [ 69 , 71 , 74 , 83 , 86 , 88 ], while persistently elevated titers are reported in 2 studies [ 72 , 73 ]. In our study, AQP4 Ab titers during follow up were available for four AQP-4 seropositive patients, of which one patient became seronegative, two patients had lower AQP-4 antibody titers, and one had persistently elevated titers (1:10,000 on cell-based assay) after several years of therapy [ 85 ].…”