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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).

ABSTRACT: BACKGROUND:Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation. METHODS:We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n?=?118) or type II (n?=?62) were randomised to 3-months oral treatment with 750?mg amoxicillin (n?=?89) or placebo (n?=?91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0-24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms. RESULTS:None of the four primary potential effect modifiers had strong evidence of modifying the treatment effect. In patients younger than 40?years the difference in mean RMDQ score between the treatment groups was -?4.0 (95%CI, -?6.9 to -?1.2), compared to -?0.5 (95%CI, -?2.3 to 1.3) in patients 40?years or older, both in favour of amoxicillin treatment (exploratory analysis). CONCLUSIONS:We did not find evidence for convincing clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes. Our results for younger age in these explorative analyses should not affect clinical treatment decisions without confirmation in future studies. TRIAL REGISTRATION:ClinicalTrials.gov NCT02323412 , First registered 23 December 2014.

SUBMITTER: Braten LCH

PROVIDER: S-EPMC7359501 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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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).

Bråten Lars Christian Haugli LCH Grøvle Lars L Espeland Ansgar A Pripp Are Hugo AH Grotle Margreth M Helllum Christian C Haugen Anne Julsrud AJ Froholdt Anne A Rolfsen Mads Peder MP Nygaard Øystein Petter ØP Lutro Olav O Kristoffersen Per Martin PM Anke Audny A Schistad Elina Iordanova EI Skouen Jan Sture JS Brox Jens Ivar JI Zwart John-Anker JA Storheim Kjersti K

BMC musculoskeletal disorders 20200713 1

<h4>Background</h4>Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previ ...[more]

PMID: 32660517

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Project description:OBJECTIVE:To 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). DESIGN:Double blind, parallel group, placebo controlled, multicentre trial. SETTING:Hospital outpatient clinics at six hospitals in Norway. PARTICIPANTS:180 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. INTERVENTIONS:Patients 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 MEASURES:The 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. RESULTS:In 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. CONCLUSIONS:In 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 REGISTRATION:ClinicalTrials.gov NCT02323412.

Project description:ObjectiveTo evaluate the cost-utility of 100 days of antibiotics in patients with chronic low back pain (LBP) and type I or II Modic changes included in the Antibiotic treatment In patients with chronic low back pain and Modic changes (AIM) study.DesignA cost-utility analysis from a societal and healthcare perspective alongside a double-blinded, parallel group, placebo, multicentre trial.SettingHospital outpatient clinics at six hospitals in Norway. The main results from the AIM study showed a small effect in back-related disability in favour of the antibiotics group, and slightly larger in those with type I Modic changes, but this effect was below the pre-defined threshold for clinically relevant effect.Participants180 patients with chronic LBP, previous disc herniation and Modic changes type I (n=118) or type II (n=62) were randomised to antibiotic treatment (n=89) or placebo-control (n=91).InterventionsOral treatment with either 750 mg amoxicillin or placebo three times daily for 100 days.Main outcome measuresQuality-adjusted life years (QALYs) by EuroQoL-5D over 12 months and costs for healthcare and productivity loss measured in Euro (€1=NOK 10), in the intention-to-treat population. Cost-utility was expressed in incremental cost-effectiveness ratio (ICER).ResultsMean (SD) total cost was €21 046 (20 105) in the amoxicillin group and €19 076 (19 356) in the placebo group, mean difference €1970 (95% CI; -3835 to 7774). Cost per QALY gained was €24 625. In those with type I Modic changes, the amoxicillin group had higher healthcare consumption than the placebo group, resulting in €39 425 per QALY gained. Given these ICERs and a willingness-to-pay threshold of €27 500 (NOK 275 000), the probability of amoxicillin being cost-effective was 51%. Even when the willingness-to-pay threshold increased to €55 000, the probability of amoxicillin being cost-effective was never higher than 53%.ConclusionsAmoxicillin treatment showed no evidence of being cost-effective for people with chronic LBP and Modic changes during 1-year follow-up.Trial registration numberClinicalTrials.gov NCT02323412.

Project description:A previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months' follow-up. The present study examines the effects of antibiotic treatment in chronic LBP patients with MCs at the level of a lumbar disc herniation, similar to the previous study. It also aims to assess the cost-effectiveness of the treatment, refine the MRI assessment of MCs, and further evaluate the impact of the treatment and the pathogenesis of MCs by studying genetic variability and the gene and protein expression of inflammatory biomarkers.A double-blinded RCT is conducted at six hospitals in Norway, comparing orally administered amoxicillin 750 mg, or placebo three times a day, over a period of 100 days in patients with chronic LBP and type I or II MCs at the level of a MRI-confirmed lumbar disc herniation within the preceding 2 years. The inclusion will be stopped when at least 80 patients are included in each of the two MC type groups. In each MC type group, the study is designed to detect (??=?0.1, ??=?0.05) a mean difference of 4 (standard deviation 5) in the Roland Morris Disability Questionnaire score between the two treatment groups (amoxicillin or placebo) at 1-year follow-up. The study includes cost-effectiveness measures. Blood samples are assessed for security measures and for possible inflammatory mediators and biomarkers at different time points. MCs are evaluated on MRI at baseline and after 12 months. A blinded intention-to-treat analysis of treatment effects will be performed in the total sample and in each MC type group.To ensure the appropriate use of antibiotic treatment, its effect in chronic LBP patients with MCs should be re-assessed. This study will investigate the effects and cost-effectiveness of amoxicillin in patients with chronic LBP and MCs at the level of a disc herniation. The study may also help to refine imaging and characterise the biomarkers of MCs.ClinicalTrials.gov, ID: NCT02323412 . Registered on 21 November 2014.

Project description:BackgroundModic Changes (MCs, magnetic resonance imaging (MRI) signal changes in the vertebral bone marrow extending from the vertebral endplate) may represent a subgroup of nonspecific chronic low back pain that could benefit from a specific management. The primary aim was to compare clinical characteristics between patients with type 1 versus type 2 MCs. The secondary aim was to explore associations between clinical characteristics and MC related short tau inversion recovery (STIR) signals.MethodsThis cross-sectional study used baseline data prospectively collected between 2015 and 2017 on the 180 patients included in the AIM-study (Antibiotics In Modic changes), a randomized controlled trial in a Norwegian hospital out-patient setting of patients with chronic low back pain, a lumbar disc herniation within the last 2 years, low back pain intensity score ≥ 5 (on a 0-10 scale) and current type 1 or type 2 MCs at the previously herniated lumbar disc level. We used prespecified clinical characteristics including self-report measures, physiologic measures and functional measures from clinical history and examination. The diagnostic accuracy of various clinical characteristics to discriminate between patients with type 1 MCs (with or without additional type 2 MCs) and patents with type 2 MCs only (not type 1) were assessed by calculating the area under the receiver-operating curve. We assessed the correlations of clinical characteristics with details of MC related STIR signal increase.ResultsNo clinical characteristic differed between patients with type 1 (n = 118) versus type 2 (but not type 1) (n = 62) MCs. The clinical characteristics showed no/minor differences or no/weak correlations with MC related STIR signal increase. Patients with a positive Springing test (at any lumbar level) had slightly less volume of STIR signal increase than those with a negative test (mean difference 1.3 on a 0-48 scale, 95% CI 0.3 to 2.3).ConclusionClinical characteristics were similar for patients with type 1 MCs and patients with type 2 MCs, and showed no clinically relevant correlations with MC related STIR signal increase.Trial registrationClinicalTrials.gov NCT02323412, First registered 23 December 2014.

Project description:PurposeModic type 1 changes/bone edema in the vertebrae are present in 6 % of the general population and 35-40 % of the low back pain population. It is strongly associated with low back pain. The aim was to test the efficacy of antibiotic treatment in patients with chronic low back pain (>6 months) and Modic type 1 changes (bone edema).MethodsThe study was a double-blind RCT with 162 patients whose only known illness was chronic LBP of greater than 6 months duration occurring after a previous disc herniation and who also had bone edema demonstrated as Modic type 1 changes in the vertebrae adjacent to the previous herniation. Patients were randomized to either 100 days of antibiotic treatment (Bioclavid) or placebo and were blindly evaluated at baseline, end of treatment and at 1-year follow-up.Outcome measuresPrimary outcome, disease-specific disability, lumbar pain. Secondary outcome leg pain, number of hours with pain last 4 weeks, global perceived health, EQ-5D thermometer, days with sick leave, bothersomeness, constant pain, magnetic resonance image (MRI).Results144 of the 162 original patients were evaluated at 1-year follow-up. The two groups were similar at baseline. The antibiotic group improved highly statistically significantly on all outcome measures and improvement continued from 100 days follow-up until 1-year follow-up. At baseline, 100 days follow-up, 1-year follow-up the disease-specific disability-RMDQ changed: antibiotic 15, 11, 5.7; placebo 15, 14, 14. Leg pain: antibiotics 5.3, 3.0, 1.4; placebo 4.0, 4.3, 4.3. Lumbar pain: antibiotics 6.7, 5.0, 3.7; placebo 6.3, 6.3, 6.3. For the outcome measures, where a clinically important effect size was defined, improvements exceeded the thresholds, and a trend towards a dose-response relationship with double dose antibiotics being more efficacious.ConclusionsThe antibiotic protocol in this study was significantly more effective for this group of patients (CLBP associated with Modic I) than placebo in all the primary and secondary outcomes.

Project description:BackgroundPrevious systematic reviews have reported positive associations between Modic changes (MCs) and low back pain (LBP), but due to their narrow scope and new primary studies, there is a need for a comprehensive systematic review. Our objectives were to investigate if MCs are associated with non-specific LBP and/or activity limitation and if such associations are modified by other factors.MethodsA protocol for this review was registered at PROSPERO prior to commencing the work (PROSPERO record: CRD42015017350). The MEDLINE, CINAHL and EMBASE databases were searched for relevant studies from first record to June 15th 2016. Prospective or retrospective cross-sectional cohort studies and case-control studies including people of all ages from general, working and clinical study populations were eligible for inclusion. Risk of bias assessment and data extraction for associations and potential modifiers were completed independently by pairs of reviewers. Meta-analysis was performed for homogeneous studies and presented as odds ratios (OR) with 95% CI.ResultsIn all, 5210 citations were identified and 31 studies were included. One study had low risk of bias. Fifteen studies (48%) reported statistically significant positive associations between MCs and LBP and one study found a statistically significant negative association. Meta-analysis performed for studies using concordant pain with provocative discography as the clinical outcome resulted in an OR of 4.01 (1.52-10.61). One of seven studies reported a statistically significant positive association between MCs and activity limitation. Lumbar disc level and disc degeneration were found to modify the association between MCs and LBP.ConclusionsThe results from this comprehensive systematic review indicate that the associations between MCs and LBP-related outcomes are inconsistent. The high risk of bias and the heterogeneity in terms of study samples, clinical outcomes and prevalence estimates of MCs and LBP may explain these findings. It is likely that new studies with low risk of bias will affect the direction and strength of these associations.

Dataset Information

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).

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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).

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