Study design: Combined prospective randomized controlled trial and observational cohort study of degenerative spondylolisthesis (DS) with an as-treated analysis.
Objective: To determine modifiers of the treatment effect (TE) of surgery (the difference between surgical and nonoperative outcomes) for DS using subgroup analysis.
Summary of background data: Spine Patient Outcomes Research Trial demonstrated a positive surgical TE for DS at the group level. However, individual characteristics may affect TE.
Methods: Patients with DS were treated with either surgery (n = 395) or nonoperative care (n = 210) and were analyzed according to treatment received. Fifty-five baseline variables were used to define subgroups for calculating the time-weighted average TE for the Oswestry Disability Index during 4 years (TE = [INCREMENT] Oswestry Disability Index(surgery)- [INCREMENT] Oswestry Disability Index(nonoperative)). Variables with significant subgroup-by-treatment interactions (P< 0.05) were simultaneously entered into a multivariate model to select independent TE predictors.
Results: All analyzed subgroups that included at least 50 patients improved significantly more with surgery than with nonoperative treatment (P< 0.05). Multivariate analyses demonstrated that age 67 years or less (TE -15.7 vs.-11.8 for age >67, P= 0.014); female sex (TE -15.6 vs.-11.2 for males, P= 0.01); the absence of stomach problems (TE -15.2 vs.-11.3 for those with stomach problems, P= 0.035); neurogenic claudication (TE -15.3 vs.-9.0 for those without claudication, P= 0.004); reflex asymmetry (TE -17.3 vs.-13.0 for those without asymmetry, P= 0.016); opioid use (TE -18.4 vs.-11.7 for those not using opioids, P< 0.001); not taking antidepressants (TE -14.5 vs.-5.4 for those on antidepressants, P= 0.014); dissatisfaction with symptoms (TE -14.5 vs.-8.3 for those satisfied or neutral, P= 0.039); and anticipating a high likelihood of improvement with surgery (TE -14.8 vs.-5.1 for anticipating a low likelihood of improvement with surgery, P= 0.019) were independently associated with greater TE.
Conclusion: Patients who met strict inclusion criteria improved more with surgery than with nonoperative treatment, regardless of other specific characteristics. However, TE varied significantly across certain subgroups.
Level of evidence: 3.