Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Patients with fibromyalgia (FM) who received up to 3.25 years of milnacipran (MLN) in a flexible-dose (≤200 mg/d) open-label (OL) study were eligible to continue into this randomized, double-blind (DB), placebo (PBO)-controlled discontinuation study, which demonstrated loss of therapeutic effect after withdrawal of long-term MLN treatment in patients who had achieved ≥50% pain improvement. The present analysis was conducted to determine whether patients from this study who met lower thresholds of pain improvement also experienced loss of therapeutic effect after discontinuing long-term MLN treatment.
Methods: After 4 weeks (OL) of continuing MLN treatment at the dose received in the prior long-term study, patients were evaluated for pain response and randomized (2:1) to continue MLN or discontinue treatment (ie, switch to PBO) for the 12-week DB withdrawal period. In patients who had received MLN ≥100 mg/d, 3 subgroups were identified based on percent of pain reduction from pre-MLN exposure: 1) ≥50%, n=150; 2) 30 to <50%, n=61; and 3) <30%, n=110. Efficacy assessments included visual analog scale pain (VAS, 0-100 mm), SF-36 Physical Component Summary (SF-36 PCS), Fibromyalgia Impact Questionnaire Revised (FIQR), and Beck Depression Inventory (BDI).
Results: In both subgroups of patients with clinically meaningful pain relief (≥50% and 30 to <50% subgroups), mean worsening of VAS pain scores from randomization to end of the DB withdrawal period was significantly greater (P<.05) in patients switched to PBO (≥50%, +17.7 mm; 30% to <50%, +8.5 mm) than in patients continuing MLN (≥50%, +8.3 mm; 30% to <50%, -0.5 mm). The absolute difference between treatment arms was similar in both subgroups (≥50%, -9.4 mm; 30 to <50%, -9.0 mm), as was the percentage of lost treatment effect after withdrawal (≥50%, 37.7%; 30 to <50%, 31.2%). Patients with ≥50% pain response also experienced notable worsening in SF-36 PCS and FIQR total scores after treatment withdrawal (P<.01, MLN vs PBO; both measures). In the subgroup with <30% pain improvement, no worsening in pain was observed in either treatment arm at endpoint (PBO, -1.1 mm; MLN, -5.3 mm; P=.14). However, patients in this subgroup experienced significant worsening in FIQR scores after withdrawal from MLN relative to those who continued treatment (P<.001). Additionally, patients in this subgroup who were withdrawn from MLN had worsened SF-36 PCS and BDI scores while patients continuing MLN experienced no worsening in these domains.
Conclusion: Significant worsening in pain after drug withdrawal was found in both subgroups of FM patients that had shown clinically meaningful responses to long-term MLN therapy (≥50%, 30 to <50% pain improvement), suggesting that the traditional ≥30% pain responder cutoff may be adequate to demonstrate efficacy in randomized withdrawal studies. Patients with <30% pain response did not experience worsening in pain following withdrawal, but did experience worsening in other symptoms, suggesting that these patients may have received long-term benefit from milnacipran treatment for some FM symptom domains despite only modest improvements in pain.
Disclosure:
D. J. Clauw,
Forest Laboratories,
5,
Forest Laboratories,
2;
P. J. Mease,
Forest Laboratories,
2,
Forest Laboratories,
5,
Forest Laboratories,
8;
R. H. Palmer,
Forest Laboratories,
3;
J. M. Trugman,
Forest Laboratories,
3;
Y. Ma,
Forest Laboratories,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-long-term-milnacipran-treatment-in-patients-meeting-different-thresholds-of-clinically-relevant-pain-relief-subgroup-analysis-of-a-double-blind-placebo-controlled-discontinuation-study/