Golimumab in Children with Chronic Recurrent Multifocal Osteomyelitis: A Case Series and Review of the Literature.

backgroundChronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory bone disease requiring immunosuppressive treatment in half of patients. Monoclonal tumor necrosis factor inhibitors (TNFi) are often used as effective second-line off-label therapies. However, paradoxical psoriasis can occur in a subset of patients exposed to monoclonal TNFi and can prompt conversion to alternate therapy if severe.

objectiveThe aim of this study was to determine the efficacy and safety of golimumab, a fully humanized TNFi, in children with CRMO, including those who develop paradoxical psoriasis after exposure to other monoclonal TNFi.

methodsA retrospective chart review was conducted of patients with CRMO who received golimumab in a single center between 01 June, 2018 and 31 December, 2020. Patients who were diagnosed before 21 years of age and followed up for CRMO at least once after receiving ≥ 3 months of golimumab were included. Extracted data included patient demographics, whole-body MRI lesion counts, clinically relevant data, laboratory results, patient-reported outcomes, and psoriasis burden. Linear mixed models with log-transformed outcomes were used to assess changes in the outcomes over time. The random effect is included in the model to account for the within-subject correlation of repeated measures. p-values and 95% confidence intervals were reported.

resultsEighteen patients were included. Patients were observed for a median of 9.95 months [interquartile range 3.84-15.64]. The median age at the initiation of golimumab was 10.95 years [9.86-13.77] and the median duration of disease between the disease onset and the initiation of golimumab was 2.60 years [1.66-3.62]. Ten patients received golimumab via intravenous route and eight patients received golimumab via subcutaneous route. The median dose was 1.64 mg/kg/month [1.46, 2]. Fourteen patients were previously treated with disease-modifying antirheumatic drugs and 17 with other TNFi. Patients treated with golimumab showed significant improvement in median physician global assessment for CRMO from 2.00 [1.00-3.00] to 0.00 [0.00-0.25] by the fourth visit (p < 0.001), with median erythrocyte sedimentation rate (ESR) decreasing significantly from 12.00 [6.75-23.75] to 5.00 [3.00-10.00] by the fourth visit (p < 0.05). The median number of lesions on MRI decreased significantly from 3.50 [2.00-5.50] to 0.50 [0.00-4.25] lesions per patient (p < 0.01). Nine out of 12 patients who had previous paradoxical psoriasis associated with adalimumab or infliximab had persistent active psoriasis at study baseline. For patients with psoriasis at study baseline, the prevalence of psoriasis had decreased from 100% to approximately 50-57% at the following visits. Of the 18 patients initiated on golimumab in this study, there was only one new case of mild psoriasis in a patient with previously resolved infliximab-associated paradoxical psoriasis. No serious infections or adverse events were noted during the study. Two patients in the study showed clinical improvement with concomitant golimumab and ustekinumab with no reported adverse side effects or increased effects in these patients over a 16-month interval, showing that this combination can be safe and effective for children with CRMO.

conclusionIn our experience, golimumab has been shown to be a safe and effective therapy for CRMO and demonstrated improvement in paradoxical psoriasis in many patients. Longer follow-up periods would be helpful to develop longer term outcomes data for patients with CRMO and overall paradoxical psoriasis risk.