Modic Change Edema in Chronic Low Back Pain Treated with Infliximab or Placebo: The BackToBasic Trial

Magnhild Hammersland Dagestad; Nils Vetti; Lars Christian Haugli Bråten; Elisabeth Gjefsen; Lars Grøvle; Kristina Gervin; Anne Julsrud Haugen; Gunnstein Bakland; Gunn Hege Marchand; Thomas Kadar; Kjersti Storheim; John-Anker Zwart; Jörg Assmus; Ansgar Espeland

doi:10.1097/BRS.0000000000005391

Modic Change Edema in Chronic Low Back Pain Treated with Infliximab or Placebo: The BackToBasic Trial

Spine (Phila Pa 1976). 2025 May 13. doi: 10.1097/BRS.0000000000005391. Online ahead of print.

Authors

Magnhild Hammersland Dagestad^{1

2}, Nils Vetti^{1

2}, Lars Christian Haugli Bråten^{3

4}, Elisabeth Gjefsen^{3

4}, Lars Grøvle⁵, Kristina Gervin³, Anne Julsrud Haugen⁵, Gunnstein Bakland^{6

7}, Gunn Hege Marchand⁸, Thomas Kadar⁹, Kjersti Storheim^{3

10}, John-Anker Zwart^{3

4}, Jörg Assmus¹¹, Ansgar Espeland^{1

2}

Affiliations

¹ Department of Radiology, Haukeland University Hospital, P.O. Box 1400, 5021 Bergen, Norway.
² Department of Clinical Medicine, University of Bergen, P.O. Box 7804, 5020 Bergen, Norway.
³ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital HF, Ulleval, Bygg 37b, P.O. Box 4956, Nydalen, 0424 Oslo, Norway.
⁴ Faculty of Medicine, University of Oslo, P.O. Box 1072 Blindern, 0316 Oslo, Norway.
⁵ Department of Rheumatology, Østfold Hospital Trust, P.O. Box 300, 1714 Grålum, Moss, Norway.
⁶ Department of Rheumatology, University Hospital of North Norway, P.O. Box 100, 9038 Tromsø, Norway.
⁷ Institute of Clinical Medicine, UiT The Arctic University, P.O. Box 6050 Stakkevollan, 9037 Tromsø, Norway.
⁸ Departement of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, P.O. Box 3250 Torgarden, 7006 Trondheim, Norway.
⁹ Department of Physical Medicine and Rehabilitation, Haukeland University Hospital, P.O. Box 1400, 5021 Bergen, Norway.
¹⁰ Faculty of Health Science, OsloMet - Oslo Metropolitan University, P.O. Box 4, St. Olavs plass, 0130 Oslo, Norway.
¹¹ Centre for Clinical Research, Haukeland University Hospital, P.O. Box 1400, 5021 Bergen, Norway.

PMID: 40358067
DOI: 10.1097/BRS.0000000000005391

Abstract

Study design: Randomized trial.

Objective: To assess whether infliximab is superior to placebo in reducing Modic change (MC) edema, and whether MC edema or apparent diffusion coefficient (ADC) values of MCs modify the effect of infliximab on disability or low back pain (LBP).

Summary of background data: In the present BackToBasic trial, infliximab did not reduce disability or LBP at 5-months follow-up in patients with chronic LBP and MC type 1. The effect on MC edema and in edema-defined subgroups is unknown.

Methods: Patients with chronic LBP and type 1 MCs were randomized to receive four infliximab infusions or placebo over 98 days. MC edema was assessed using short tau inversion recovery imaging. Primary edema variables were maximum baseline edema volume (Volmax) ≥25% of vertebral body marrow (yes/no) and reduced edema at 6 months (yes/no). Maximum MC-related ADC value (0-100%) was measured at baseline. Outcomes at 5 months were the Oswestry Disability Index (ODI, 0-100, primary outcome) and LBP intensity (0-10). The analyses included logistic regression and linear mixed-effects models.

Results: 128 patients (mean age 43 years, 84 women) were included, of which78 were treated per protocol (PP). The odds ratio for reduced MC edema at 6 months in the infliximab vs placebo group was 2.2 (95% confidence interval [CI] 0.8, 5.8; P=0.12) in the primary PP analysis and 2.1 (95% CI 1.02, 4.5; P=0.04) in the total sample. Neither MC edema nor ADC values modified the effect of infliximab on ODI or LBP intensity. At 5 months, the effect in the Volmax ≥25% group was -4.2 ODI points (95% CI -11.4, 3.1; primary PP analysis).

Conclusion: Infliximab had no clinically relevant edema reducing effect. MC edema did not modify the effect of infliximab on disability or LBP, nor did the MC-related ADC value.

Level of evidence: Level 2.

Keywords: Modic changes; STIR; edema; infliximab; low back pain; lumbar spine; magnetic resonance imaging; prospective studies; randomized controlled trial; treatment.