Beyond NSAIDS : second-line therapeutic agents for chronic recurrent multifocal osteomyelitis


O Leary DM, Mac Dermott EJ, Wilson AG, Killeen OG


National Centre for Paediatric Rheumatology, Our Lady's Children's Hospital School of Medicine, University College Dublin National Children's Research Centre, Dublin


Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease affecting bone. Untreated CRMO can result in complications such as vertebral compression fractures and leg length discrepancy. First line treatment is with non-steroidal anti-inflammatory drugs (NSAIDs) with a reported response rate of 50-80%. Limited data is available on the efficacy of second-line treatments which include methotrexate, bisphosphonates and biologic agents.


To describe the experience of the National Centre for Paediatric Rheumatology (NCPR) treating currently attending CRMO patients with second-line agents.


Retrospective chart review of current patients requiring second-line agents attending the National Centre for Paediatric Rheumatology. Persistent active disease was defined as persistent pain with tenderness/warmth or persistent bone oedema on MRI in at least one lesion site after >4 weeks treatment (CARRA consensus treatment guidelines). Response to treatment was defined as clinical and/or radiological improvement without complete resolution. Remission was defined as normal ESR, absence of clinically active lesions, resolution of marrow oedema on MRI and absence of new lesions on whole-body MRI (modified CARRA criteria for treatment failure).


Clinical charts of 30 patients with CRMO were reviewed. Second-line treatment was required in 60%. The indications for second-line treatment were persistent active disease on NSAIDS or the presence of spinal lesions or cosmetically significant mandibular lesion.
A total of 19 patients received methotrexate, either alone (n=8 )or in combination with a biologic agent (n=11). Three received pamidronate; none achieved remission and all subsequently received methotrexate +/- biologic. Of those who received methotrexate monotherapy, 1 is in remission on treatment, 1 remains in remission off treatment, 6 have responded but not achieved remission.
Of those on biologic combination therapy, 2 patients are in remission, 1 discontinued treatment due to a hypersensitivity reaction. The remaining patients improved but have yet to achieve remission.


Treatment with second-line agents has led to a symptomatic improvement in all patients.
Combination therapy of methotrexate and a biologic agent may be the most favourable option but randomised controlled trials with clearly defined response and remission criteria are required.