Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial

Abstract

Importance: Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors and often result in therapy discontinuation. Small studies suggest that acupuncture may decrease aromatase inhibitor-related joint symptoms.

Objective: To determine the effect of acupuncture in reducing aromatase inhibitor-related joint pain.

Design, setting, and patients: Randomized clinical trial conducted at 11 academic centers and clinical sites in the United States from March 2012 to February 2017 (final date of follow-up, September 5, 2017). Eligible patients were postmenopausal women with early-stage breast cancer who were taking an aromatase inhibitor and scored at least 3 on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain).

Interventions: Patients were randomized 2:1:1 to the true acupuncture (n = 110), sham acupuncture (n = 59), or waitlist control (n = 57) group. True acupuncture and sham acupuncture protocols consisted of 12 acupuncture sessions over 6 weeks (2 sessions per week), followed by 1 session per week for 6 weeks. The waitlist control group did not receive any intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52.

Main outcomes and measures: The primary end point was the 6-week BPI-WP score. Mean 6-week BPI-WP scores were compared by study group using linear regression, adjusted for baseline pain and stratification factors (clinically meaningful difference specified as 2 points).

Results: Among 226 randomized patients (mean [SD] age, 60.7 [8.6] years; 88% white; mean [SD] baseline BPI-WP score, 6.6 [1.5]), 206 (91.1%) completed the trial. From baseline to 6 weeks, the mean observed BPI-WP score decreased by 2.05 points (reduced pain) in the true acupuncture group, by 1.07 points in the sham acupuncture group, and by 0.99 points in the waitlist control group. The adjusted difference for true acupuncture vs sham acupuncture was 0.92 points (95% CI, 0.20-1.65; P = .01) and for true acupuncture vs waitlist control was 0.96 points (95% CI, 0.24-1.67; P = .01). Patients in the true acupuncture group experienced more grade 1 bruising compared with patients in the sham acupuncture group (47% vs 25%; P = .01).

Conclusions and relevance: Among postmenopausal women with early-stage breast cancer and aromatase inhibitor-related arthralgias, true acupuncture compared with sham acupuncture or with waitlist control resulted in a statistically significant reduction in joint pain at 6 weeks, although the observed improvement was of uncertain clinical importance.

Trial registration: ClinicalTrials.gov Identifier: NCT01535066.

Figure 1.. Flow of Randomized Patients for the Effect of True Acupuncture vs Sham Acupuncture and True Acupuncture vs Waitlist Control on Joint Pain Using the 6-Week Brief Pain Inventory-Short Form Worst Pain Score

BPI indicates Brief Pain Inventory. ^aData were not collected to report the number of patients screened for eligibility prior to randomization. ^bPatients’ status as major deviations began immediately in the course of follow-up and was applied to both the 6-week and 12-week analyses. ^cOne patient who was not available for 6-week evaluation was evaluated at 12 weeks.

Figure 2.. Linear Mixed-Model Results Through 24 Weeks for Selected Brief Pain Inventory-Short Form End Points

Horizontal bars at baseline indicate the observed baseline means. Vertical bars indicate the interquartile range (IQR) for each study group at each assessment time and are offset by a small margin to show the IQR for each group. Fitted regression lines for each group are also shown, with P values for the effect of intervention on Brief Pain Inventory-Short Form outcomes derived from multivariable linear mixed-model analyses with a random effect for patient, adjusting for continuous time, the baseline score, and indicator variables for study sites, and report values for comparisons between true acupuncture vs sham acupuncture and true acupuncture vs waitlist control for week 6, 12, 16, 20, and 24 assessment times. A, P = .04 (vs sham acupuncture); P<.001 (vs waitlist control). B, P = .18 (vs sham acupuncture); P = .003 (vs waitlist control). C, P = .08 (vs sham acupuncture); P = .003 (vs waitlist control). D, P = .02 (vs sham acupuncture); P<.001 (vs waitlist control).