Factors associated with preference for sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodiesterase 5 inhibitor therapy: post hoc analysis of data from a multicentre, randomized, open-label, crossover study.

OBJECTIVES: To determine if baseline characteristics, treatment efficacy, psychosocial outcomes or tolerability were associated with patient preference for sildenafil citrate (sildenafil) or tadalafil for treating erectile dysfunction (ED) in men naive to phosphodiesterase 5 inhibitor therapy. PATIENTS AND METHODS: In an open-label, crossover study of sildenafil (25, 50 or 100 mg) and tadalafil (10 or 20 mg), dosed as needed, after a 4-week baseline assessment, 367 men with ED were randomly assigned to sildenafil followed by tadalafil or vice versa (8-week dose optimization and 4-week assessment phase for each treatment period). Patients completing both periods chose which treatment they preferred for an 8-week extension phase. Bivariate logistic regression and stepwise logistic regression were used to determine if any baseline characteristics or post-baseline measurements were associated with the patients' treatment preference. Baseline variables examined were age, race, ED aetiology/duration, body mass index, smoking status, alcohol consumption, vital signs, comorbid medical conditions, and baseline scores for the International Index of Erectile Function (IIEF) domains, Psychological and Interpersonal Relationship Scales (PAIRS) domains, and Sexual Encounter Profile (SEP) diary questions. Post-baseline variables examined were therapy sequence, dosage, and differences in IIEF and PAIRS domains, SEP scores, in number/timing of sexual attempts and in the severity of side-effects (overall patient perception). RESULTS: Of 291 patients completing both treatments and indicating a preference, 85 (29%) preferred sildenafil and 206 (71%) preferred tadalafil. Variables were individually analysed using bivariate analysis; one baseline characteristic (presence/absence of hyperlipidaemia) and 13 post-baseline measurements were significantly associated with the patients' treatment preference. Variables were analysed as a group using stepwise logistic regression; a set of six post-baseline factors was identified as significantly associated with patient preference. Dosage choice, reductions in the PAIRS time concerns domain, IIEF intercourse satisfaction domain improvements, smaller side-effect severity scores, more sexual attempts, and increased SEP4 scores (satisfaction with erection hardness) during the tadalafil or sildenafil treatment periods were all significantly associated with preference for tadalafil or sildenafil. CONCLUSIONS: We identified no baseline characteristics that prospectively distinguish patients who will prefer tadalafil or sildenafil. Patient differences in time concerns, dosage choice, intercourse satisfaction, treatment tolerability, number of sexual attempts and satisfaction with erection hardness were the set of factors most significantly associated with treatment preference, and the preference observed for tadalafil (71%) or sildenafil (29%) might be substantially accounted for by differences in these factors during the tadalafil and sildenafil treatment periods.

Efficacy and safety of tadalafil 5, 10, and 20 mg in Japanese men with erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVES: To investigate the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in Japanese men with erectile dysfunction (ED). METHODS: This multicenter, randomized, double-blind, placebo-controlled, 12-week study enrolled 343 Japanese men with ED. The men were stratified into those with mild, moderate, or severe ED and then randomly assigned 1:1:1:1 to placebo and 5 mg, 10 mg, and 20 mg tadalafil. Co-primary outcomes were the International Index of Erectile Function erectile function domain score, the percentage of "yes" responses to the Sexual Encounter Profile Diary Questions 2 and 3, and tolerability. Secondary outcomes included the International Index of Erectile Function intercourse satisfaction and overall satisfaction domain scores and the percentage of "yes" responses to a global assessment question. RESULTS: The least square mean change from baseline was 7.5, 9.1, and 9.4 for 5, 10, and 20 mg tadalafil versus 2.1 for placebo for the International Index of Erectile Function erectile function domain; 28.5, 36.0, and 36.5 for 5, 10, and 20 mg tadalafil versus 8.6 for placebo for Sexual Encounter Profile question 2; and 34.3, 47.3, and 50.8 for 5, 10, and 20 mg tadalafil versus 12.3 for placebo for Sexual Encounter Profile question 3, respectively (P <0.001 for all doses and all measures). Patients taking tadalafil had significantly greater changes from baseline for the intercourse satisfaction and overall satisfaction domains compared with patients taking placebo (P <0.001). Also, 76.5%, 81.4%, and 83.7% of patients taking 5, 10, and 20 mg tadalafil, respectively, reported improved erections (global assessment question) versus 31.4% of patients taking placebo (P <0.001). Most (98%) treatment-emergent adverse events were mild or moderate in severity. One patient (tadalafil 5 mg) discontinued because of an adverse event (ureteral calculus). Of the 343 patients, 302 (88%) completed the study. No deaths were reported. CONCLUSIONS: All doses of tadalafil studied were efficacious and well tolerated in Japanese men with ED.

Cardiovascular safety update of Tadalafil: retrospective analysis of data from placebo-controlled and open-label clinical trials of Tadalafil with as needed, three times-per-week or once-a-day dosing.

Because most men with erectile dysfunction have underlying vascular disease, it is important to update the cardiovascular safety profile of medications used in the treatment of erectile dysfunction. This retrospective analysis evaluated serious cardiovascular treatment-emergent adverse events (CVTEAEs) reported in 36 clinical trials of tadalafil, a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction. A serious CVTEAE was defined as myocardial infarction, cardiovascular death, or cerebrovascular death. In the 36 trials, 12,487 men (mean age 55 years) with erectile dysfunction received tadalafil, with 5,771 patient-years (PYs) of exposure, and 2,047 men (mean age 56 years) received placebo, with 460 PYs of exposure. Tadalafil 2 to 50 mg was taken as needed, 3 times/week, or once a day. Co-morbidities at baseline included hypertension (31%), diabetes (21%), hyperlipidemia (17%), and coronary artery disease (5%). Across all trials, the incidence rate of serious CVTEAEs was 0.40/100 PYs in tadalafil-treated patients and 0.43/100 PYs in placebo-treated patients. In patients taking tadalafil as needed, 3 times/week, or once a day, the incidence rates of serious CVTEAEs ranged from 0.17 to 0.54/100 PYs across placebo-controlled and open-label trials. In conclusion, the incidence rates of serious CVTEAEs were comparable among men with erectile dysfunction taking tadalafil as needed, 3 times/week, or once a day, and these rates were also comparable with those in placebo-treated patients. In this clinical trial population of men with erectile dysfunction, tadalafil was not associated with an increased risk for serious cardiovascular adverse events.

Cellular immune response in HIV-infected patients with histoplasmosis.

The relationship of immunity to Histoplasma capsulatum and CD4 count in HIV-1-infected patients is unknown. Samples of blood from people with HIV infection and from HIV-negative volunteers were assessed for immune responsiveness to the histoplasmin antigen using proliferation and interferon-gamma production as indicators of immunity. Results of histoplasmin skin tests, lymphoproliferative responses (LPR), and interferon-gamma production were positive in 9 of 20 (45%) HIV-negative controls, and in vitro measurements agreed highly with skin test reactivity. Among HIV-1-infected patients with recent histoplasmosis, skin test results were positive in none, LPR results were positive in 14%, and interferon-gamma production in 18%. Among HIV-1-infected patients with CD4 counts between 200 and 500 cells/mm(3), LPR was positive in 8% and interferon-gamma production in 33%, and among those with CD4 counts >500 cells/mm(3), LPR was positive in 31% and interferon-gamma production in 46%. In conclusion, immune responsiveness to H. capsulatum was depressed in HIV-1-infected persons with CD4 counts between 200 and 500 cells/mm(3), but approached normal in those with CD4 counts >500 cells/mm(3).