Oedema on STIR modified the effect of amoxicillin as treatment for chronic low back pain with Modic changes\u2014subgroup analysis of a randomized trial

Abstract

ObjectiveTo evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level).MethodsIn a prospective trial (AIM), 180 patients (25–64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0–24 scale) at 1 year. Mean RMDQ score difference between the groups at 1 year defined the treatment effect; 4 RMDQ points defined the minimal clinically important effect. Predefined baseline MRI features of MCs at the index level(s) were investigated as potential effect modifiers. The predefined primary hypothesis was a better effect of amoxicillin when short tau inversion recovery (STIR) shows more MC-related high signal. To evaluate this hypothesis, we pre-constructed a composite variable with three categories (STIR1/2/3). STIR3 implied MC-related STIR signal increases with volume ≥ 25% and height > 50% of vertebral body and maximum intensity increase ≥ 25% and presence on both sides of the disc. As pre-planned, interaction with treatment was analysed using ANCOVA in the per protocol population (n = 155).ResultsThe STIR3 composite group (n = 41) and STIR signal volume ≥ 25% alone (n = 45) modified the treatment effect of amoxicillin. As hypothesised, STIR3 patients reported the largest effect (− 5.1 RMDQ points; 95% CI − 8.2 to − 1.9; p for interaction = 0.008).ConclusionsPredefined subgroups with abundant MC-related index-level oedema on STIR modified the effect of amoxicillin. This finding needs replication and further support.Key Points• In the primary analysis of the AIM trial, the effect of amoxicillin in patients with chronic low back pain and type 1 or 2 MCs did not reach the predefined cut-off for clinical importance.• In the present MRI subgroup analysis of AIM, predefined subgroups with abundant MC-related oedema on STIR reported an effect of amoxicillin.• This finding requires replication and further support.