FP.03 The spine fracture burden in boys with DMD treated with the novel dissociative steroid vamorolone versus deflazacort and prednisone

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Vertebral fractures (VF) cause excess morbidity in glucocorticoid (GC)-treated DMD. Vamorolone (VAM/VBP15) is a dissociative steroid that retains anti-inflammatory properties with reduced positive transcriptional activity, leading to fewer side effects in pre-clinical studies compared with classic GC. We determined VF burden in VAM-treated boys vs. boys treated with daily deflazacort (DEFLAZ_DAILY), daily prednisolone (PRED_DAILY), and intermittent prednisolone (PRED_INT). 39 boys from VBP15-LTE study were compared to 68 boys from FOR-DMD (all ambulatory, steroid-naïve). In VBP15-LTE, boys 4 to <7 years-old initiated VAM 0.25, 0.75, 2.0, or 6.0 mg/kg/d for 6 months, followed by permitted dose escalations/de-escalations for 2 years. In FOR-DMD, boys 4 to <8 years-old were randomized to DEFLAZ_DAILY (0.9mg/kg/d), PRED_DAILY (0.75mg/kg/d) or PRED_INT (0.75mg/kg/d 10 days on/off). VF were read centrally on x-rays (Genant method, T4 to L4) after 30 (VAM) or 36 (classic GC) months. In the VAM group, VF parameters were adjusted (adj) for shorter duration by a factor of 1.2 (36/30 months), as appropriate. Mean age of boys on classic GC was 8.8±1.1 and on VAM 8.0±1.0 years. VF burdens: 1. VF prevalence: PRED_DAILY 7/24 boys (29.2%), DEFLAZ_DAILY 4/21 (19.0%), VAM 4/39 (10.3%; 12.3% adj), PRED_INT 0/23; 2. Highest fracture severity: DEFLAZ_DAILY moderate (n=1, 9.5%), PRED_DAILY mild (N=7, 100%), VAM mild (n=4; 100%), and PRED_INT N/A; 3. Average number of VF/child with VF: PRED_DAILY 1.3, DEFLAZ_DAILY 1.3, VAM 1.0; 1.2 adj and PRED_INT 0; 4. Maximum Spine Deformity Index (SDI, sum of VF Grades): DEFLAZ_DAILY 6, PRED_DAILY 4, VAM 1; PRED_INT 0; and 5. Average SDI/child with VF: DEFLAZ_DAILY 3.0, PRED_DAILY 2.7, VAM 1.0; 1.2 adj, and PRED_INT 0. VF burden was higher on PRED_DAILY and DEFLAZ_DAILY than VAM but lowest on PRED_INT. VAM may be a bone-sparing strategy to improve muscle strength. Longer-term follow-up is needed to assess comparative effects on VF burden relative to muscle strength.