Per Martin Kristoffersen1,2, Lars C H Bråten3, Nils Vetti4,5, Lars Grøvle6, Christian Hellum7, Kjersti Storheim3,8, John-Anker Zwart3,9, Jörg Assmus10, Ansgar Espeland4,5. 1. Department of Radiology, Haukeland University Hospital, Jonas Liesvei 65, 5021, Bergen, Norway. per.martin.kristoffersen@helse-bergen.no. 2. Department of Clinical Medicine, University of Bergen, P.O. Box 7804, 5020, Bergen, Norway. per.martin.kristoffersen@helse-bergen.no. 3. Research and Communication Unit for Musculoskeletal Health (FORMI), Oslo University Hospital HF, Ulleval, Bygg 37b, P.O. Box 4956, 0424, Oslo, Nydalen, Norway. 4. Department of Radiology, Haukeland University Hospital, Jonas Liesvei 65, 5021, Bergen, Norway. 5. Department of Clinical Medicine, University of Bergen, P.O. Box 7804, 5020, Bergen, Norway. 6. Department of Rheumatology, Østfold Hospital Trust, P.O. Box 300, 1714, Grålum, Norway. 7. Division of Orthopaedic Surgery, Oslo University Hospital Ulleval, P.O. Box 4950, Nydalen, 0424, Oslo, Norway. 8. Faculty of Health Science, OsloMet - Oslo Metropolitan University, P.O. Box 4, St. Olavs plass, 0130, Oslo, Norway. 9. Faculty of Medicine, University of Oslo, P.O. Box 1072, Blindern, 0316, Oslo, Norway. 10. Competence Centre for Clinical Research, Haukeland University Hospital, Jonas Liesvei 65, 5021, Bergen, Norway.
Abstract
OBJECTIVE: To evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level). METHODS: In a prospective trial (AIM), 180 patients (25-64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0-24 scale) at 1 year. Mean RMDQ score difference between the groups at 1 year defined the treatment effect; 4 RMDQ points defined the minimal clinically important effect. Predefined baseline MRI features of MCs at the index level(s) were investigated as potential effect modifiers. The predefined primary hypothesis was a better effect of amoxicillin when short tau inversion recovery (STIR) shows more MC-related high signal. To evaluate this hypothesis, we pre-constructed a composite variable with three categories (STIR1/2/3). STIR3 implied MC-related STIR signal increases with volume ≥ 25% and height > 50% of vertebral body and maximum intensity increase ≥ 25% and presence on both sides of the disc. As pre-planned, interaction with treatment was analysed using ANCOVA in the per protocol population (n = 155). RESULTS: The STIR3 composite group (n = 41) and STIR signal volume ≥ 25% alone (n = 45) modified the treatment effect of amoxicillin. As hypothesised, STIR3 patients reported the largest effect (- 5.1 RMDQ points; 95% CI - 8.2 to - 1.9; p for interaction = 0.008). CONCLUSIONS: Predefined subgroups with abundant MC-related index-level oedema on STIR modified the effect of amoxicillin. This finding needs replication and further support. KEY POINTS: • In the primary analysis of the AIM trial, the effect of amoxicillin in patients with chronic low back pain and type 1 or 2 MCs did not reach the predefined cut-off for clinical importance. • In the present MRI subgroup analysis of AIM, predefined subgroups with abundant MC-related oedema on STIR reported an effect of amoxicillin. • This finding requires replication and further support.
RCT Entities:
OBJECTIVE: To evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level). METHODS: In a prospective trial (AIM), 180 patients (25-64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0-24 scale) at 1 year. Mean RMDQ score difference between the groups at 1 year defined the treatment effect; 4 RMDQ points defined the minimal clinically important effect. Predefined baseline MRI features of MCs at the index level(s) were investigated as potential effect modifiers. The predefined primary hypothesis was a better effect of amoxicillin when short tau inversion recovery (STIR) shows more MC-related high signal. To evaluate this hypothesis, we pre-constructed a composite variable with three categories (STIR1/2/3). STIR3 implied MC-related STIR signal increases with volume ≥ 25% and height > 50% of vertebral body and maximum intensity increase ≥ 25% and presence on both sides of the disc. As pre-planned, interaction with treatment was analysed using ANCOVA in the per protocol population (n = 155). RESULTS: The STIR3 composite group (n = 41) and STIR signal volume ≥ 25% alone (n = 45) modified the treatment effect of amoxicillin. As hypothesised, STIR3 patients reported the largest effect (- 5.1 RMDQ points; 95% CI - 8.2 to - 1.9; p for interaction = 0.008). CONCLUSIONS: Predefined subgroups with abundant MC-related index-level oedema on STIR modified the effect of amoxicillin. This finding needs replication and further support. KEY POINTS: • In the primary analysis of the AIM trial, the effect of amoxicillin in patients with chronic low back pain and type 1 or 2 MCs did not reach the predefined cut-off for clinical importance. • In the present MRI subgroup analysis of AIM, predefined subgroups with abundant MC-related oedema on STIR reported an effect of amoxicillin. • This finding requires replication and further support.
Entities:
Keywords:
Amoxicillin; Low back pain; Magnetic resonance imaging; Prospective studies; Spine
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