Influence of baseline variables on changes in International Prostate Symptom Score after combined therapy with dutasteride plus tamsulosin or either monotherapy in patients with benign prostatic hyperplasia and lower urinary tract symptoms: 4-year results of the CombAT study

Objective To examine, using post hoc analysis, the influence of baseline variables on changes in international prostate symptom score (IPSS), maximum urinary flow rate (Q(max)) and IPSS quality of life (QoL) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with either the -blocker tamsulosin or the dual 5-alpha reductase inhibitor dutasteride, alone or in combination, as part of the 4-year Combination of Avodart and Tamsulosin (CombAT) study. Patients and Methods CombAT was a 4-year, multicentre, randomized, double-blind, parallel-group study in 4844 men 50 years of age with a clinical diagnosis of BPH by medical history and physical examination, an IPSS 12 points, prostate volume (PV) 30mL, total serum PSA level 1.5ng/mL, and Q(max) >5mL/s and 15mL/s with a minimum voided volume 125mL. Eligible subjects were randomized to receive oral daily tamsulosin, 0.4mg; dutasteride, 0.5mg; or a combination of both. Baseline variable subgroups analysed were as follows: PV (30 to <40; 40 to <60; 60 to <80; 80mL), PSA level (1.5 to <2.5; 2.5 to <4; 4ng/mL), age (median: <66, 66 years), IPSS (median: <16, 16; IPSS thresholds, <20, 20), IPSS QoL score (question 8, Q8) (median: <4, 4), Q(max) (median: <10.4, 10.4mL/s), BPH impact index (BII) (median: <5, 5) and body mass index (BMI, median: <26.8, 26.8kg/m(2)). Within each baseline variable subgroup, changes in IPSS, Q(max) and IPSS QoL Q8 from baseline were evaluated using a generalized linear model with effects for baseline IPSS, Q(max) or IPSS QoL Q8 and treatment group at each post-baseline assessment up to and including the month 48 visit using a last observation carried forward approach. The treatment comparisons of combination therapy vs dutasteride and combination therapy vs tamsulosin were performed from the general linear model with statistical significance defined as P 0.01. Results Combination therapy resulted in a significantly greater improvement from baseline IPSS at 48 months vs tamsulosin monotherapy across all baseline subgroups. The benefit of combination therapy over dutasteride was confined to groups with lower baseline PV (<60mL) and PSA (<4ng/mL). In groups with baseline PV 60mL and PSA 4ng/mL, dutasteride and combination therapy show similar improvements in symptoms. Combination therapy resulted in significantly improved Q(max) compared with tamsulosin but not dutasteride monotherapy. Q(max) improvement appeared to increase with PV and PSA level in combination therapy subjects. The proportion of subjects with an IPSS QoL 2 (at least mostly satisfied) at 48 months was significantly higher with combination therapy than with dutasteride for subgroups with PV 40-60mL and PSA level <4ng/mL and than with tamsulosin for all PSA subgroups and PV subgroups 40mL. Conclusions CombAT data support the use of long-term combination therapy with dutasteride and tamsulosin in patients considered at risk for progression of BPH, as determined by high PV (30mL) and high PSA (1.5ng/mL). Combination therapy, dutasteride monotherapy and tamsulosin monotherapy all improved Q(max), but to different extents (combination therapy > dutasteride >> tamsulosin), suggesting that dutasteride contributes most to the Q(max) benefit in combination therapy. Combination therapy provided consistent improvement over tamsulosin in LUTS across all analysed baseline variables at 48 months. Compared with dutasteride, the superiority of combination therapy at 48 months was shown in patients with PV <60mL or PSA <4ng/mL.