Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Milnacipran 100 Mg/Day for the Management of Fibromyalgia: Results From a 2-Week Discontinuation Phase
Saxe1, Philippe A., Arnold2, Lesley M., Gendreau3, R. Michael, Spera4, Allan, Gendreau3, Judy, Wang4, Yong
A randomized controlled trial in fibromyalgia (FM) patients demonstrated significant improvements with milnacipran (MLN) 100 mg/d vs placebo (PBO) in measures of pain, global status, and physical function. Patients completing 12 weeks of stable-dose treatment were rerandomized to a 2-week, double-blind, placebo-controlled discontinuation phase to assess durability of efficacy and possible withdrawal effects of MLN 100 mg/d.
Patients completing the stable-dose phase were assigned to a discontinuation phase where patients initially assigned to PBO remained on PBO (n=359) and patients treated with MLN 100 mg/d were rerandomized and switched to PBO (n=178) or maintained on MLN 100 mg/d (n=178). Efficacy assessments included changes during the discontinuation phase in 24-h recall pain (e-diary), Patient Global Impression of Change (PGIC), SF-36 Physical Component Summary (PCS), Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), Multidimensional Fatigue Inventory (MFI), and Multiple Ability Self-Report Questionnaire (MASQ).
715 patients entered the discontinuation phase; 5 patients discontinued before the final study visit (2 PBO; 2 MLN rerandomized to PBO; 1 continuing on MLN). Two weeks after removal of active drug, the proportion of 3-measure composite responders ('30% improvement in 24-h recall pain; PGIC <=2; and >=6-point improvement in SF-36 PCS) was significantly reduced in patients rerandomized from MLN to PBO compared with patients maintained on MLN (P<.05). Patients rerandomized from MLN to PBO had an 11.4% increase in 24-h recall pain scores during the discontinuation phase compared with 5.2% and 3.2% increases for patients remaining on MLN or PBO, respectively. Patients rerandomized to PBO also had at least a 2-fold worse change in BPI average pain, PGIC, FIQ, SF-36 PCS, MFI, and MASQ scores than patients remaining on PBO or MLN. In patients discontinuing MLN and rerandomized to PBO, supine systolic blood pressure returned to prestudy baseline values, diastolic blood pressure returned to within 1 mm Hg, and pulse returned to within 4 bpm; values for patients continuing with MLN treatment remained unchanged. Incidences of newly-emergent adverse events (NEAE) were lower in patients discontinuing MLN (16.3%) than in patients remaining on MLN (18.0%) or PBO (19.2%). On abrupt discontinuation of MLN, no NEAE occurred in >=2% of patients.
Patients discontinuing milnacipran experienced a loss of therapeutic effect in multiple efficacy parameters, including the proportion of 3-measure composite responders compared with patients maintained on milnacipran. Abrupt withdrawal of milnacipran did not appear to result in new safety concerns in this study.
To cite this abstract, please use the following information:
Saxe, Philippe A., Arnold, Lesley M., Gendreau, R. Michael, Spera, Allan, Gendreau, Judy, Wang, Yong; A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Milnacipran 100 Mg/Day for the Management of Fibromyalgia: Results From a 2-Week Discontinuation Phase [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1421