Perineuromal Botulinum Toxin Injection for War-Related Postamputation Pain: A Pragmatic, Multicenter, Comparative Effectiveness Study

Objectives: To determine the comparative effectiveness of botulinum toxin (BT) injections versus comprehensive medical and surgical treatment (CMST) for war-related postamputation pain. Design: A prospective, comparative-effectiveness study evaluating outcomes in patients treated with BT or CMST at 2 Ukrainian hospitals. Setting: Two Ukrainian hospitals treating war-related injuries. Participants: Patients with at least 2 out of 10 residual limb pain (RLP) or phantom limb pain (PLP) were included. Interventions: In the BT group (N=39), patients received BT injections around neuromas in the residual limb (perineuromal), subcutaneously over sensitized tissue, and/or as trigger point injections, plus physical and pharmacotherapy as indicated. The CMST group (N=127) received injections, surgical therapies, physical and pharmacotherapies, and integrative treatments. Main Outcome Measures: The primary outcome measures were mean reduction in RLP and PLP at 3-month follow-up. Secondary outcome measures were RLP and PLP, and success was defined as ≥30% decrease in postamputation pain. Results: At 3 months, the reduction in PLP scores was greater in the CMST than the BT group (2.0±2.0 vs 3.5±3.5, P=.002). For RLP, the reduction did not differ significantly between groups (BT 2.0±2.5 vs CMST 3.0±2.8, P=.50). Conversely, the reduction in PLP at 1 month favored BT (4.0±3.5 vs 1.0±2.5, P>.001), with no significant difference in RLP reduction. Responder rates favored BT for PLP at 1 month (68.6% vs 43.1%, P=.01), and CMST for RLP (97.1% vs 63.2%, P<.001) but not PLP at 3 months. Conclusions: On some measures, BT outperforms or is noninferior to CMST at 1 month but not 3 months, suggesting that multimodal treatment is superior in the long term.