Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study)
Authors: Bråten Lars Christian Haugli , Grøvle Lars , Espeland Ansgar , Pripp Are Hugo , Grotle Margreth , Helllum Christian , Haugen Anne Julsrud , Froholdt Anne , Rolfsen Mads Peder , Nygaard Øystein Petter , Lutro Olav , Kristoffersen Per Martin , Anke Audny , Schistad Elina Iordanova , Skouen Jan Sture , Brox Jens Ivar , Zwart John-Anker , Storheim Kjersti ,   The AIM-study group, Wilhelmsen Maja , Fors Terese , Kjos Guro , Østhus Ida Beate , Marchand Gunn Hege , Lurud Britt Elin , Granvigen Fredrik , Andersen Hege , Rao Vidar , Kadar Thomas Istvan , Claussen Siv Krüger , Andersen Erling , Vetti Nils , Aßmus Jörg , Randen Sigrun , Presberg Hilde , Wigemyr Monica , Pedersen Linda Margareth , Winsvold Bendik Slagsvold , Gammelsrud Karianne Wiger , Vigeland Maria Dehli , Lie Benedicte Alexandra , Flåm Siri Tennebø , Vigeland Magnus Dehli , Thorsø Marianne , Huneide Knut Morten , Sørensen Veronica , Holmgard Thor Einar 
Published: July 2020

Abstract
Background
Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation.

Methods
We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n = 118) or type II (n = 62) were randomised to 3-months oral treatment with 750 mg amoxicillin (n = 89) or placebo (n = 91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0–24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms.

Results
None of the four primary potential effect modifiers had strong evidence of modifying the treatment effect. In patients younger than 40 years the difference in mean RMDQ score between the treatment groups was − 4.0 (95%CI, − 6.9 to − 1.2), compared to − 0.5 (95%CI, − 2.3 to 1.3) in patients 40 years or older, both in favour of amoxicillin treatment (exploratory analysis).

Conclusions
We did not find evidence for convincing clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes. Our results for younger age in these explorative analyses should not affect clinical treatment decisions without confirmation in future studies.

Trial registration
ClinicalTrials.gov NCT02323412, First registered 23 December 2014.