Chronic Back Pain – facilitated by Dr James Dickinson

The two journal articles discussed were:

  1. Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy                     Reference: Hanne B. Albert; Joan S. Sorensen; Berit S. Christensen; Claus Manniche. Eur Spine J (2013) 22:697-707
  2. Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae? Reference: Hanne B. Albert; Peter Lambert; Jess Rollason; Joan S. Sorensen; Tony Worthington; Mogens B. Pedersen; Hanne S. Norgaard; Ann Vernallis; Federik Busch; Claus Manniche; Tom Elliot. Eur Spine J (2013) 22:690-696

The Journal club reviewed the trial, which has excited controversy because it was heralded in the press with stories of being a ground-breaking new cure for back pain, and that the author should be in the running for a Nobel Prize. Others, not surprisingly were skeptical (McCartney BMJ blog.)

The components of the trial were:

P    Chronic back pain 6 months duration, after previous disc herniation, with adjacent bone edema, (Mobic type 2)

I     Antibiotic amoxicillin/clavulanate three times daily for 10 weeks. (main analysis, but groups were divided to high and low dose: half received Amoxycillin 500/Clavulanate125, while half received double that dose.

C     placebo, in identical capsules, same dose.

O     Disease -specific disability and lumbar pain.

The inclusion criteria were strict. There was consecutive enrolment of eligible patients.

Modic changes: high reliability.

Randomisation was performed by a central lab, and was blinded to the clinicians and patients. We observed that the numbers in the randomisation were uneven: 90 active and 72 placebo with no explanation, but the two subgroups for high and low dose were exactly even. WE wondered whether the uneven rate was due to some design feature, to the dose response component of the study.

We noted that the dose response component was added late in the design, at the request of the Danish research council, then was not analysed for. We found it disturbing that the Research Council should ask for such a change, especially if it interfered with the power of the study. However, we thought that the researchers should have performed the full analysis, which would not be much more effort, nor take more space than what they did.

The allocation to groups was balanced, except that the active group had slightly worse disease as measure by a lower proportion with only type 1 changes, and “non-significant” differences for other measures.

Assessment of patient was by self-report questionnaires. These were obtained at the clinic visits and patients were not allowed to leave until they were complete, giving a 100% completion rate for the baseline visit, 91% at the 100 days, and 90% at the end of one year. Xray and MRI changes were noted, but the main outcome was the improvement in patient-important pain outcomes, including days away from work. These included the Roland Morris Disease-specific Questionnaire and the Lumbar Pain Rating Scale. To our group they seemed appropriate.

Outcomes: High completion rate: 90% It was odd that 2 were dropped out because they were >65 yrs. Patients reported gradual improvement: over 6-8 weeks, then further improvement in the period after the drugs had ceased, which is biologically plausible.

There were more GI side effects in antibiotic group: as expected.

There was a trend towards greater effect for double dose antibiotics.

The conclusions are appropriately cautious: they do not encourage widespread use, only among those who fit the criteria.

While the results of the trial are impressive, there was some concern about the biological mechanism and plausibility of the approach. The second paper, describing the bacteriological research behind the theory does have convincing evidence that bacteria do inhabit the discs.

Overall we decided that the trial is convincing. We would like to be sure about what happened in the randomisation: JD was deputed to write to the author.

PG felt that the result needs replication, and will write to the UK ???? to suggest this is an important topic for contracted research.

Background theory:

Various studies show that disc material is infected with propionobacterium acnes.

Uncontrolled study showed improvement with amoxicillin.

Therefore trial.

Bacteria in discs: 50%