Three months of treatment with amoxicillin did not provide a clinically important benefit in patients with chronic low back pain and Modic changes, a study published in the British Medical Journal (BMJ) has concluded.
The AIM study, a double blind, randomised, placebo controlled, multi-centre trial, was authored by Lars Christian Haugli Bråten (Oslo University Hospital, Oslo, Norway) and colleagues, and sought to assess the efficacy of three months of antibiotic treatment in patients with chronic low back pain, previous disc herniation and vertebral endplate changes.
According to the authors, the pathogenesis of Modic changes is unclear, with one hypothesis that they can be caused by low grade bacterial discitis caused by cutibacterium acnes (C acnes), an aerotolerant, gram-positive anaerobe bacteria, and a common skin commensal.
A systematic review found only one randomised trial assessing the efficacy of antibiotic treatment in patients with low back pain. This trial reported a substantial effect of three months of antibiotic treatment compared with placebo—between group difference of 8.3 points on the Roland-Morris Disability Questionnaire (RMDQ) at one year follow up—in patients with chronic low back pain, prior disc herniation, and type 1 Modic changes. However, Bråten and colleagues note that the trial conclusion has been questioned, based upon almost no improvement in the control group, no evaluation of blinding efficacy, and a high proportion of participants with previous disc surgery, and thus a potential risk of bacterial contamination.
Bråten and the study team aimed to replicate the findings of the previous randomised trial, which evaluated the efficacy and harm of three months of oral treatment with amoxicillin at one-year follow-up in patients with chronic low back pain and type 1 or 2 Modic changes at the level of a previous lumbar disc herniation.
The study team recruited patients from outpatient clinics at six hospitals in Norway from June 2015 to September 2017. Inclusion criteria were age 18–65 years; low back pain for more than six months, with intensity of at least five on a 0–10 numerical rating scale, lumbar disc herniation on magnetic resonance imaging in the preceding two years; and type 1 or type 2 Modic changes. Patients who had surgery for disc herniation in the past year, or antibiotic treatment in the past month, were excluded from the trial.
Patients were randomised at a median of 13 days after inclusion into either three months of oral treatment with amoxicillin 750mg three times daily or placebo (maize starch). Care providers gave each patient a prescription with a computer-generated allocation number to be used at the dedicated hospital pharmacies. All care providers, research staff, statisticians, and patients were unaware of the assignment group during the data collection.
The primary outcome was the score on the validated Norwegian version of the RMDQ at one year follow-up. RMDQ scores range from 0–24. Higher scores indicate more severe pain and disability. Secondary outcomes included pain related disability (Oswestry Disability Index), low back pain intensity (0-10 numerical rating scale), and health related quality of life.
Of the 582 patients assessed for eligibility, 180 underwent randomisation; 118 with type 1 Modic changes and 62 with type 2 Modic changes. Bråten and colleagues found that at one year, the mean RMDQ score had reduced since baseline in both treatment groups (-3.7 points in the amoxicillin group and -2.1 points in the placebo group). The adjusted mean difference in RMDQ score between the amoxicillin group and the placebo group at one year was -1.6 points (95% confidence interval -3.1 to 0, P=0.04), while the adjusted between group difference of the mean RMDQ score was -2.3 (95% confidence interval -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.
Additionally, in the amoxicillin group, 50 patients (56%) had at least one drug related adverse event, compared with 31 patients (34%) in the placebo group. One or more serious adverse events occurred in six patients (7%) in the amoxicillin group and two patients (2%) in the placebo group; none was related to the study drug. In the amoxicillin group, 11 patients (12%) discontinued or paused the study drug because of adverse events compared with two patients (2%) in the placebo group. No deaths occurred during the trial.
Bråten and colleagues concluded that the study was unable to replicate the findings of the previous randomised trial, and did not show any clinically important effect from three months of oral antibiotic treatment in patients with low back pain, Modic changes and a former herniated disc. The findings, they note, do not support the use of antibiotic treatment for chronic low back pain and Modic changes.