Background/Purpose: Majeed syndrome is a rare, autosomal recessive disorder that presents with early onset chronic recurrent multifocal osteomyelitis (CRMO) and microcytic congenital dyserythropoietic anaemia caused by a mutation in the LPIN2 gene (OMIM reference #609628). Occasionally, Majeed syndrome is associated with neutrophilic dermatosis. The chronic inflammatory bone disease starting before the age of two has previously been described having a recalcitrant debilitating course resulting in permanent joint contractures and growth disturbances after years of chronic inflammation. Aim: To report the long-term effect of IL-1 inhibition in two patients with Majeed syndrome.

Methods: Whole-body MRIs were performed at presentation, after 3 months and at regular yearly intervals using T1 weighted images and short tau inversion recovery (STIR) images. Patiens: Two brothers with consanguinity of the parents were diagnosed with Majeed syndrome. LPIN2 gene resequencing of both patients revealed a homozygous 2-bp deletion (c.1312_1313delCT) resulting in a premature stop codon (p.Leu438fs-16X). Both patients were refractory to the treatment with corticosteroids and etanercept. Demonstration of the clinical and biochemical efficacy of IL-1 inhibition by anakinra led to the treatment of both children with canakinumab.

Results: Canakinumab 4 mg/kg subcutaneously every 4-5 weeks has now been given for 5 years as monotherapy. During the past years no fever related to the CRMO has been observed. The children have been well without any clinical signs of osteomyelitis, no physical restraints, and no skin changes. The drug has been well tolerated and without any side effects. At no time corticosteroids and NSAIDs have been given after canakinumab was initiated. Repeated whole-body MRIs showed disappearance of osteomyelytic lesions in both patients already after few months. Whole-body MRIs have been performed yearly during the past 5 years showing no signs of relapse in Sib A. Sib B had normal whole-body MRIs during the first 4 years but showed transient, subclinical osteomyelytic lesion at the ossis pubis after 4 years and a subclinical lesion at the right corpus tibiae after 5 years. Growth of height has been normal for both children growing along the 25^th percentile. ESR was still moderately elevated during the first year of treatment but normalized thereafter in both children. However, within the past year the ESR has been variably elevated (from 12 to 29 mm/hr) in Sib B. During the years hemoglobin has been within normal range for both children. Erythroblasts have been slightly elevated in Sib A (0.05-0.12 x 10⁹/L), but not in Sib B (<0.01 x 10⁹/L).

Conclusion: Sustained effect of IL-1 inhibition by canakinumab for the treatment of Majeed syndrome is described. The drug is well tolerated and although costly, the prevention of a debilitating course of this rare, chronic disease seems to be achievable by canakinumab.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/canakinumab-monotherapy-for-the-treatment-of-majeed-syndrome-five-year-experience/