Cytokine Patterns as Predictors of Antibiotic Treatment Effect in Chronic Low Back Pain with Modic Changes: Subgroup Analyses of a Randomized Trial (AIM Study)

Lars Christian Haugli Bråten; Elisabeth Gjefsen; Kristina Gervin; Are Hugo Pripp; Jan Sture Skouen; Elina Schistad; Linda Margareth Pedersen; Monica Wigemyr; Kaja Kristine Selmer; Hans Christian Dalsbotten Aass; Guro Goll; Jens Ivar Brox; Ansgar Espeland; Lars Grøvle; John-Anker Zwart; Kjersti Storheim; AIM-study group

doi:10.2147/JPR.S406079

Cytokine Patterns as Predictors of Antibiotic Treatment Effect in Chronic Low Back Pain with Modic Changes: Subgroup Analyses of a Randomized Trial (AIM Study)

J Pain Res. 2023 May 23:16:1713-1724. doi: 10.2147/JPR.S406079. eCollection 2023.

Authors

Lars Christian Haugli Bråten¹, Elisabeth Gjefsen^{1

2}, Kristina Gervin¹, Are Hugo Pripp³, Jan Sture Skouen⁴, Elina Schistad⁵, Linda Margareth Pedersen¹, Monica Wigemyr¹, Kaja Kristine Selmer¹, Hans Christian Dalsbotten Aass⁶, Guro Goll⁷, Jens Ivar Brox⁵, Ansgar Espeland^{8

9}, Lars Grøvle¹⁰, John-Anker Zwart^{1

2}, Kjersti Storheim^{1

11}; AIM-study group

Affiliations

¹ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital HF, Oslo, Norway.
² Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Oslo Centre of Biostatistics and Epidemiology Research Support Services, Oslo University Hospital Ulleval, Oslo, Norway.
⁴ Department of Physical Medicine and Rehabilitation, Haukeland University Hospital, Bergen, Norway.
⁵ Department of Physical Medicine and Rehabilitation, Oslo University Hospital HF, Oslo, Norway.
⁶ Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
⁷ Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway.
⁸ Department of Radiology, Haukeland University Hospital, Bergen, Norway.
⁹ Department of Clinical Medicine, University of Bergen, Bergen, Norway.
¹⁰ Department of Rheumatology, Østfold Hospital Trust, Grålum, Norway.
¹¹ Oslo Metropolitan University, Department of Physiotherapy, Oslo, Norway.

Abstract

Objective: Randomized trials testing the effect of antibiotics for chronic low back pain (LBP) with vertebral bone marrow changes on MRI (Modic changes) report inconsistent results. A proposed explanation is subgroups with low grade discitis where antibiotics are effective, but there is currently no method to identify such subgroups. The objective of the present study was to evaluate whether distinct patterns of serum cytokine levels predict any treatment effect of oral amoxicillin at one-year follow-up in patients with chronic low back pain and Modic changes at the level of a previous lumbar disc herniation.

Design: We used data from an overpowered, randomized, placebo-controlled trial (the AIM study) that tested 100 days of oral 750 mg amoxicillin vs placebo three times daily in hospital outpatients with chronic (>6 months) LBP with pain intensity ≥5 on a 0-10 numerical rating scale and Modic changes type 1 (oedema type) or 2 (fatty type). We measured serum levels of 40 inflammatory cytokines at baseline and analysed six predefined potential predictors of treatment effect based on cytokine patterns in 78 randomized patients; three analyses with recursive partitioning, one based on cluster analysis and two based on principal component analyses. The primary outcome was the Roland-Morris Disability Questionnaire score at one-year follow-up in the intention to treat population. The methodology and overall results of the AIM study were published previously.

Results: The 78 patients were 25-62 years old and 47 (60%) were women. None of the three recursive partitioning analyses resulted in any suggested subgroups. Of all main analyses, the largest effect estimate (mean difference between antibiotic and placebo groups) was seen in a subgroup not predefined as of main interest (Cluster category 3+4; -2.0, 95% CI: -5.2-1.3, RMDQ points; p-value for interaction 0.54).

Conclusion: Patterns of inflammatory serum cytokine levels did not predict treatment effect of amoxicillin in patients with chronic LBP and Modic changes.

Clinical trial registration number: ClinicalTrials.gov (identifier: NCT02323412).

Keywords: Modic changes; cytokines; infection; inflammation; low back pain.

Publication types

Case Reports
Clinical Trial

Associated data

ClinicalTrials.gov/NCT02323412

Grants and funding

Funding was granted by governmental organisations Helse Sør-Øst (grant No 2015090), Helse Vest (grant No 911938 and 911891) and KLINBEFORSK (grant no: 2017201), which had no part in the planning, performing, or reporting of the trial.