Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial

Abstract

ObjectiveTo assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes).DesignDouble blind, parallel group, placebo controlled, multicentre trial.SettingHospital outpatient clinics at six hospitals in Norway.Participants180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017.InterventionsPatients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription.Main outcome measuresThe primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4.ResultsIn the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was −1.6 (95% confidence interval −3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was −2.3 (−4.2 to−0.4, P=0.02) for patients with type 1 Modic changes and −0.1 (−2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group.ConclusionsIn this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes.Trial registrationClinicalTrials.gov NCT02323412.

Cost–utility analysis of antibiotic treatment in patients with chronic low back pain and Modic changes: results from a randomised, placebo-controlled trial in Norway (the AIM study)

“…Our results support the main results from the AIM study which detected no clinically important benefit of amoxicillin compared to placebo during 12 months of follow-up. 14 The present cost-utility analysis also extends the findings from the AIM study by demonstrating that the patients in the amoxicillin group used more healthcare than the placebo group. In particular, the use of physiotherapy and manual therapy was substantially higher in the amoxicillin group.…”

“…A placebo controlled randomised trial 10 reported substantial effect of 100 days of high-dosage antibiotic treatment on painrelated disability in patients with chronic LBP and type I Modic changes. The recent AIM replication study 14 from Norway found a small, but not clinically important benefit of amoxicillin vs placebo on pain-related disability for patients with type I or type II Modic changes. In patients with type I Modic changes the benefit was slightly better, but still not clinically important.…”

Short tau inversion recovery MRI of Modic changes: a reliability study

“…Such data were included in articles on spondylarthritis (1)(2)(3)(4)(5), fractures (6), Modic changes (MCs) (7), hemangiomas (8), and pedicle screw loosening (9). However, all but one (6) of these reliability studies had only two observers, most (1,3-5,7-9) had small patient samples (n ¼ [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], only one (8) included measurements (of signal intensities); the spondylarthritis studies were limited to lesion detection (1)(2)(3)(4)(5). Reliability estimates differed widely in these heterogeneous studies where radiologists and non-radiologists interpreted various fat-suppressed 1.5-T or 3-T series.…”

“…The association between MCs and pain is inconsistent (13)(14)(15)(16), but edema type MCs might be symptomatic (17)(18)(19). Mechanical, autoimmune, and infectious explanations for MCs have been proposed (20), and various treatments have been and are being tested (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Reliable evaluation of the STIR findings is required to validate their relevance to symptoms and treatment (35)(36)(37).…”

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)

“…A randomised placebo controlled trial published in 2013 reported that three months of antibiotic treatment offered substantial improvement of symptoms in patients with chronic low back pain and type I Modic changes [4]. The AIM-study (Antibiotics In Modic changes), a reassessment and replication study of the former trial from 2013, did not find any clinically important difference in outcome between the treatment groups at three or 12 months follow-up [5]. There was however a small difference between the groups and an increased variance in outcome measure in the amoxicillin group compared to the placebo group, that may suggest a possible treatment effect in subgroups [6].…”