Cost-Effectiveness of Monotherapy versus Polypharmacy in Cervicobrachial Symptoms: A Nationwide Multicenter Analysis.

INTRODUCTION

Cervicobrachial symptoms are common causes of disability worldwide, yet the cost-effectiveness of combination therapy versus monotherapy remains unclear. In this nationwide multicenter study, we aimed to compare the economic value of multiple-drug therapy with that of monotherapy for cervicobrachial symptoms.

METHODS

This prospective observational study, conducted through the Japanese Society for Spine Surgery and Related Research, included 261 adults with cervicobrachial symptoms across 28 institutions (July 2020 to July 2022). Patients received monotherapy (n=112) or multiple-drug therapy (n=149) using five pre-specified agents: loxoprofen, celecoxib, acetaminophen, tramadol-acetaminophen, and pregabalin. The primary outcome was quality-adjusted life years (QALYs), calculated from monthly EuroQol 5-Dimension 5-Level assessments over six months. The secondary outcomes were drug costs and incremental cost-effectiveness ratios (ICERs), evaluated against Japan's reference threshold of 5,000,000 JPY per QALY.

RESULTS

Mean QALY gains were similar between the monotherapy (0.00267±0.00544) and multiple-drug therapy (0.00284±0.00774) groups, with no statistically significant difference (p>0.05). However, total drug costs were substantially higher with multiple-drug therapy (19,243 JPY vs. 8,275 JPY). ICERs were more favorable for monotherapy (3,093,957 JPY/QALY) than for multiple-drug therapy (6,781,101 JPY/QALY). Among agents used as monotherapy, loxoprofen (744,409 JPY/QALY) and acetaminophen (781,293 JPY/QALY) showed the most favorable cost-effectiveness profiles, whereas tramadol-acetaminophen (6,370,451 JPY/QALY) and pregabalin (10,995,651 JPY/QALY) had the least favorable cost-effectiveness. Most QALY gains occurred during the first three months in both groups.

CONCLUSIONS

Multiple-drug therapy approximately doubled pharmaceutical costs without providing additional QALY gains over six months. Monotherapy, particularly with non-steroidal anti-inflammatory drugs or acetaminophen, offers superior cost-effectiveness and should be prioritized as first-line treatment. These findings underscore the need for restraint in polypharmacy and provide real-world evidence to guide clinical decision-making and national healthcare policy.