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

Abstract

Objective To 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).

Methods In 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).

Results The 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).

Conclusions Predefined 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.