Nebulized formoterol provides added benefits to tiotropium treatment in chronic obstructive pulmonary disease.
BACKGROUND
The use of one or more long-acting bronchodilators is key in the maintenance therapy of chronic obstructive pulmonary disease (COPD). This analysis pooled the results of two double-blind studies evaluating the efficacy and safety of adding nebulized formoterol fumarate inhalation solution (FFIS) to maintenance tiotropium (TIO) treatment.


METHODS
Following a run-in period of 7-14 days with once-daily TIO 18 microg, COPD subjects (> or =25% to <65% predicted forced expiratory volume in 1 second [FEV(1)]) were randomized to twice-daily FFIS 20 microg (n=145) or nebulized placebo (PLA, n=140) while continuing on maintenance TIO for 6 weeks. Efficacy was measured using serial spirometry, transition dyspnea index (TDI), rescue albuterol use, and St. George's Respiratory Questionnaire (SGRQ).


RESULTS
The mean standardized area under the curve for FEV(1) over 3 hours (FEV(1)AUC(0-3)), the primary efficacy variable, was significantly higher in the FFIS/TIO group than the PLA/TIO group on day 1 (140 mL difference, P<0.0001) and week 6 (192 mL difference, P<0.0001). Mean TDI scores in the FFIS/TIO and PLA/TIO groups were 1.97 and 0.67, respectively (P=0.0001). Mean albuterol use declined in the FFIS/TIO group from 2.6 to 1.5 puffs/day compared with little change in the PLA/TIO group (P<0.0001). SGRQ scores were similar between treatment groups with the exception of the symptoms score, which improved in the FFIS/TIO group (-5.8) compared with PLA/TIO (-1.0), and more FFIS/TIO-treated subjects experienced a clinically significant improvement in total SGRQ score. More PLA/TIO-treated subjects than FFIS/TIO-treated subjects experienced adverse events (AEs) (45.7% vs. 31.0%) and COPD exacerbations (7.9% vs. 3.4%).


CONCLUSIONS
The addition of FFIS to maintenance TIO treatment for moderate to severe COPD results in significantly improved FEV(1) and dyspnea, decreased rescue medication use, and a lower incidence of AEs and COPD exacerbations. The addition of FFIS to TIO yields clinically and statistically significant benefits for COPD patients and might be of long-term benefit.
Tashkin
Donald P
DP
David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. dtashkin@mednet.ucla.edu
Hanania
Nicola A
NA
McGinty
Joe
J
Denis-Mize
Kimberly
K
Chaudry
Imtiaz
I
D000368:Aged; D000420:Albuterol / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000188:drug therapy; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012129:Respiratory Function Tests; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000627:therapeutic use*; D000069447:Tiotropium Bromide
D001993:Bronchodilator Agents; D004983:Ethanolamines; D012602:Scopolamine Derivatives; D000420:Albuterol; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide