Early pain response to duloxetine predicts better outcomes in patients with chronic low back pain (CLBP), according to a post hoc responder analysis of 4 studies reported in the Journal of Pain Research.1 The study also found that patients with multiple pain sites had an overall better response to duloxetine than patients with isolated CLBP. CLBP is defined as low back pain that lasts >3 months.2
The pooled data was gathered from 4 double-blind randomized placebo-controlled trials of 60 mg duloxetine given daily to adult patients (n=1295; mean age, 55.3; 57.5% women) with CLBP for 12 to 14 weeks. The trials were conducted in the United States (ClinicalTrials.gov identifier: NCT00408876); the United States and Europe (ClinicalTrials.gov identifier: NCT00767806); Europe, Brazil, and Mexico (ClinicalTrials.gov identifier: NCT00424593); and Japan (ClinicalTrials.gov identifier: NCT01855919).
The primary outcome was the number of patients who achieved a ≥30% reduction in the Brief Pain Inventory (BPI) average pain score; the secondary outcome was a ≥50% reduction in BPI average pain score. Patients in the Japanese trial used the Michigan Body Map (MBM) to self-report their painful sites.
The responder variables across the trials included early pain reduction (≥15% pain reduction at week 2), sex, age, baseline BPI average pain score, duration of CLBP, and number of painful body sites. Two of the trials prohibited the use of concomitant pain medicine (eg, NSAIDs, acetaminophen, opioids) other than for rescue purposes.
Of the patients treated with duloxetine, 59.7% achieved a response of ≥30% reduction in BPI score vs 47.8% in the placebo group (P <.001). The secondary response of ≥50% reduction in BPI score was 48.6% in the duloxetine group vs 35.1% in the placebo group (P <.001).
Patients treated with duloxetine who achieved early improvement were more likely to achieve later pain reduction response: ≥30% (relative risk [RR], 2.91; 95% CI, 2.30-3.67) and ≥50% (RR, 3.24; 95% CI, 2.44-4.31). Women were more likely than men to achieve ≥30% pain reduction (RR, 1.14; 95% CI, 1.00-1.30) and ≥50% (RR, 1.17; 95% CI, 0.99-1.38).
Although only 1 trial assessed pain at ≥2 sites, multisite pain vs isolated CLBP was shown to predict response to duloxetine for ≥30% pain reduction (RR, 1.22; 95% CI, 0.95-1.56) and ≥50% pain reduction, (RR, 1.20; 95% CI, 0.88-1.62). Moreover, pain at ≥2 sites also predicted a greater response to duloxetine at the end of 12 to 14 weeks of treatment for both the primary and secondary outcomes (P <.001).
“The presence of multiple painful sites, including the low back, is thought to result from changes in the central nervous system, particularly reduced activity of descending inhibitory pathways, which amplify pain perception,” explain the researchers. “Although limited, our analysis suggests that the number of painful body sites may be a predictor of response to duloxetine. If confirmed in subsequent studies, the [Michigan Body Map] may be useful for predicting the likelihood that individual patients with CLBP will respond to duloxetine.”
Summary and Clinical Applicability
The study demonstrated that patients who experienced pain reduction with 60 mg duloxetine early in their treatment course predicted better overall outcomes. Patients with ≥2 painful sites had a better response to duloxetine than patients with isolated CLBP.
Limitations and Disclosures
Sinichi Konno has received consulting fees and honoraria from Eli Lilly Japan K.K. and Shionogi & Co. Ltd and has received research funding from Shionogi & Co. Ltd. Levent Alev, Hiroyuki Enomoto, Shinji Fujikoshi, Kei Ogawa, and Aki Yoshikawa are employees of Eli Lilly Japan K.K. Mitsuhiro Ishida and Toshinaga Tsuji areemployees and minor stock holders of Shionogi & Co. Ltd. Levent Alev and ShinjiFujikoshi hold shares in Eli Lilly and Company.