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Objectives To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-PsA (NCT01087788), an ongoing Phase 3 trial in patients with psoriatic arthritis (PsA). Methods Patients were randomised 1:1:1 to placebo, 200 mg CZP every 2 weeks (Q2W) or 400 mg CZP every 4 weeks (Q4W). Patients could have had exposure to one previous tumour necrosis factor (TNF) inhibitor therapy. Primary endpoints were American College of Rheumatology 20% (ACR20) response at week 12 and modified Total Sharp Score change from baseline at week 24. Secondary endpoints included; Psoriatic Arthritis Response Criteria (PsARC) score, Health Assessment Questionnaire Disability Index (HAQ-DI), Psoriasis Area and Severity Index, Leeds Enthesitis Index, Leeds Dactylitis Index, and Modified Nail Psoriasis Severity Index. Results Of 409 patients randomised, 368 completed 24 weeks of treatment. ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo (58.0% and 51.9% vs 24.3% (p<0.001)) at week 12, with improvements observed by week 1. There was a statistically significant improvement in physical function from baseline, measured by HAQ-DI in CZP patients compared with placebo (−0.50 vs −0.19, p<0.001) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo (78.3% and 77.0% vs 33.1% (p<0.001)). Sustained improvements were observed in psoriatic skin involvement, enthesitis, dactylitis and nail disease. Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure. No new safety signals were observed. Conclusions Rapid improvements in the signs and symptoms of PsA, including joints, skin, enthesitis, dactylitis and nail disease were observed across both CZP dosing regimens.

Objectives To report the effect of different imputation methodologies on the assessment of radiographic progression in clinical trials. Methods The 216-week RAPID-psoriatic arthritis (PsA) (NCT01087788) trial of certolizumab pegol (CZP) in patients with active PsA was double-blind and placebo-controlled until week 24. A primary end point was change from baseline in modified Total Sharp Score(s) (mTSS). Prespecified imputation methodology in patients with fewer than two analysable mTSS used minimum observed baseline score for missing baseline values and maximum observed week 24 score for missing week 24 values. Post hoc analyses used alternative methods of imputation in patients with fewer than two analysable mTSS. mTSS non-progressors were defined as patients with ≤0 (predefined) or ≤0.5 (post hoc) change in mTSS from baseline to week 24. Baseline mTSS and C-reactive protein levels as predictors of radiographic progression were investigated. Results 409 patients were randomised. Baseline demographics were similar between groups. Prespecified imputation analysis inappropriately overestimated radiographic progression (least squares mean placebo, 28.9; CZP, 18.3; p≥0.05). Multiple post hoc analyses demonstrated that CZP inhibited radiographic progression compared with placebo, particularly in patients with high baseline mTSS and C-reactive protein levels. mTSS non-progression rate was higher in CZP than placebo groups in all analyses. Conclusions Inappropriate prespecified imputation methodology resulted in an unrealistic assessment of progression in all arms. Methodologies for imputing missing radiographic data can greatly affect assessment and reporting of mTSS progression.

BackgroundPrevious reports of RAPID-PsA (NCT01087788) have demonstrated the efficacy of certolizumab pegol (CZP) in patients (pts) with psoriatic arthritis (PsA) to Week (Wk) 96 of treatment.1ObjectivesHere we report the efficacy of CZP for the treatment of psoriatic skin manifestations in PsA pts over 96 wks, including pts with and without prior anti-TNF exposure and pts with severe skin involvement at baseline (BL).MethodsRAPID-PsA1 was double-blind and placebo-controlled to Wk24, dose-blind to Wk48 and open-label to Wk216. Pts had active PsA, had failed ≥1 DMARD and ≤40% of pts could have received 1 prior anti-TNF. Pts were randomized at BL to either placebo or CZP (200mg Q2W/400mg Q4W, following 400mg loading dose at Wks 0, 2, 4). Primary clinical endpoint was Wk12 ACR20 response.2 Here we present skin data for pts originally randomized to CZP and with BL skin involvement ≥3% body surface area (BSA). Outcomes presented are psoriasis area and severity index (PASI) responses, physician's global assessment of psoriasis (PGA) and dermatology life quality index (DLQI). Data are shown as both observed and imputed values. Non-responder imputation (NRI) was used for categorical outcomes; last observation carried forward (LOCF) for continuous outcomes. Outcomes are presented for pts with or without prior anti-TNF exposure, or for pts with severe BL skin involvement (BL PASI ≥10).Results409 pts were randomized and 273 received CZP from Wk0. CZP pts with ≥3% skin involvement at BL (166 pts, 60.8%) had a mean of 24.2% BSA affected by psoriasis and a mean PASI of 12.0 at BL. The primary endpoint of RAPID-PsA was met (ACR20[NRI]: 58.0%, 51.9% vs 24.3%; for CZP 200mg Q2W, 400mg Q4W vs placebo) and ACR responses were maintained to Wk96 (ACR20[NRI]: 60.1% at Wk24 and 64.1% at Wk96, combined CZP doses). Improvements in skin outcomes were observed to Wk96 of CZP treatment (Table A), with similar efficacy seen with both dose regimens (PASI90[NRI]: Wk24: 46.7% and 35.5%; Wk96: 48.9% and 38.2%, for 200mg Q2W and 400mg Q4W, respectively). Efficacy was also maintained in pts with severe skin involvement at BL (PASI ≥10) (PASI90[NRI]: Wk24: 59.5% and 47.1%; Wk96: 45.9% and 47.1%, for 200mg Q2W and 400mg Q4W, respectively). In these pts, greater improvements were observed in PASI responses, as well as the patient-reported measure DLQI, when compared to all pts analyzed (Table A). Similar improvements in skin outcomes were observed in patients with and without prior anti-TNF exposure (Table B).ConclusionsImprovements in skin outcomes, observed in PsA patients treated with CZP to Wk24, were maintained to Wk96 of treatment in patients with and without prior anti-TNF exposure. Patients with severe skin involvement at BL showed greater improvements in skin outcomes. Similar efficacy was observed with both CZP dosing regimen.ReferencesMease P. J. Ann Rheum Dis 2014;73(S2):90.Mease P. J. Arthritis Rheum 2013;65(10):S132–133AcknowledgementsThe authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma.Disclosure of InterestM. Khraishi Grant/research support from: Abbott, Amgen and Pfizer, B. Hoepken Employee of: UCB Pharma, O. Davies Shareholder of: UCB Pharma, Employee of: UCB Pharma, T. Arledge Employee of: UCB Pharma, L. Peterson Employee of: UCB Pharma, P. Mease Grant/research support from: (Abbott) AbbVie, Amgen, BiogenIdec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott) AbbVie, Amgen, BiogenIdec, BMS, Celgene, Covagen, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Speakers bureau: (Abbott) AbbVie, Amgen, BiogenIdec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Pfizer, UCB Pharma.

Background RAPID-PsA (NCT01087788) investigates the efficacy and safety of certolizumab pegol (CZP) in psoriatic arthritis (PsA).1 Objectives To analyse radiographic progression in PsA patients (pts) in the RAPID-PsA study using different imputation methods and assess the treatment effect of CZP in pts with and without identified baseline (BL) risk factors for progression. Methods The ongoing 158-week (wk) RAPID-PsA trial recruited pts with active PsA who failed ≥1 DMARD. Pts were randomized 1:1:1 to placebo (PBO), CZP 400mg Q4W or 200mg Q2W following loading dose. Data was evaluated in the Randomized Set. Radiographic progression analyses were assessed at Wk24 using the modified Total Sharp Score (mTSS, primary end point). The pre-specified imputation for change from baseline (CFB) in mTSS for pts with <2 analyzable X-rays used minimum observed BL score (0) and maximum observed Wk24 score (365.5) for missing values. Post-hoc analyses used alternative methods of imputation for pts with <2 analyzable X-rays including no imputation, imputation with the median, or mean CFB mTSS. The same post-hoc imputation approach was used to calculate % non-progressors at Wk24 (mTSS ≤0.5). Inhibition of radiographic progression was also analyzed according to BL mTSS (≤ or > median) and BL CRP levels (≤ or >15mg/L). Results 409pts were randomized. BL demographics were similar between groups. The pre-specified imputation analysis implausibly overestimated radiographic progression in all arms including PBO (Table). Post-hoc conventional analyses showed that CZP inhibited radiographic progression compared to PBO (Table). Pts with mTSS ≤6 (median score) or CRP ≤15mg/L at BL showed little radiographic progression in both the CZP and PBO groups. CZP (combined dose arm) decreased radiographic progression, vs PBO, in pts with BL mTSS >6 (0.08 vs 0.54, p<0.01) or CRP >15mg/L (0.08 vs 0.51, p<0.05). Higher BL mTSS and elevated CRP were also associated with a higher rate of non-progression in CZP vs PBO groups (95.1 vs 74.1 and 96.2 vs 78.3 for BL mTSS >6 and CRP >15mg/L, respectively). Image/graph Conclusions Pre-specified imputation overestimated radiographic progression in all treatment arms including PBO. Conventional imputation methods showed that CZP inhibited radiographic progression in PsA pts, particularly in pts with identified higher risk of progression. References Mease P. Ann Rheum Dis 2012;71(Suppl3):150 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Employee of: Imaging Rheumatology bv., R. Fleischmann Grant/research support from: Genetech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, AstraZeneca, Janssen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, Novartis, Astellas, AstraZeneca, Janssen, HGS, J. Wollenhaupt Grant/research support from: UCB Pharma, Consultant for: UCB Pharma, A. Deodhar Grant/research support from: UCB Pharma, Abbott, Amgen, Janssen, Novartis, Consultant for: UCB Pharma, Abbott, Speakers bureau: Abbott, Novartis, D. Kielar Shareholder of: UCB Pharma, Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, B. Hoepken Shareholder of: UCB Pharma, Employee of: UCB Pharma, T. Arledge Shareholder of: UCB Pharma, Employee of: UCB Pharma, P. Mease Grant/research support from: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma

Background Certolizumab pegol (CZP), a PEGylated Fc-free anti-TNF, has shown efficacy in reducing signs and symptoms of psoriatic arthritis (PsA) in RAPID-PsA (NCT01087788).1 Objectives To report the efficacy of CZP in PsA patients (pts) with and without prior anti-TNF exposure and to assess the impact of level of baseline skin involvement on PASI response. Methods The ongoing 158-week (wk) Phase 3 RAPID-PsA trial is double-blind and placebo (PBO)-controlled to Wk24.1 Recruited pts had active PsA, had failed ≥1 DMARD and could have experienced secondary failure to 1 prior anti-TNF. Pts were randomized 1:1:1 to PBO every 2 wks (Q2W), or 400mg CZP at Wk0, 2 and 4 (loading dose) followed by either 200mg CZP Q2W or 400mg CZP every 4 wks (Q4W). Clinical primary endpoint was ACR20 at Wk12. ACR20 was also investigated for pts with and without prior anti-TNF exposure. PASI responses were measured in pts with ≥3% body surface area skin involvement at baseline (BL). Post-hoc analyses of PASI response by BL PASI score (BL PASI <10 vs ≥10) were conducted. NRI was used for ACR and PASI responses. Analyses were performed on the Randomized Set (RS). Results 409 pts were randomized. BL demographics were similar between groups. 19.1% and 19.8% of PBO and CZP (combined arms) pts received prior anti-TNF. ACR20 at Wk12 was significantly higher in the CZP 200mg Q2W and CZP 400mg Q4W arms vs PBO (58.0% and 51.9% vs 24.3% [p<0.001 for both]) and was observed as early as Wk1.1 At Wk24, PASI75 response in pts with skin involvement (61.6% of RS) was 62.2% with CZP 200mg Q2W and 60.5% with CZP 400mg Q4W vs 15.1% PBO (p<0.001 for both). PASI75 and PASI90 at Wk12 and 24 was higher in pts with PASI ≥10 at BL vs <10 (Figure). ACR20 at Wk24 was similar between CZP 200mg Q2W and CZP 400mg Q4W arms, and greater vs PBO both in pts with (61.3% and 56.5% vs 11.5%) and without (64.5% and 56.3% vs 26.4%) prior anti-TNF exposure. Adverse events (AEs) occurred in 62% vs 68%, and serious AEs in 7% vs 4%, in CZP (combined arms) vs PBO pts, respectively. Two deaths occurred up to Wk24, one sudden death of unknown cause (CZP 400mg Q4W) and one myocardial infarct (CZP 200mg Q2W). No new safety signals were observed. Image/graph Conclusions Rapid improvements in the signs and symptoms of PsA and skin manifestations of psoriasis were observed across both CZP dosing regimens. Pts with higher BL PASI were more likely to achieve a PASI75 and PASI90 response. Similar ACR response rates with CZP were observed in pts with and without prior anti-TNF exposure. References Mease P. Arthritis Rheum 2012;64(10):1107 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest P. Mease Grant/research support from: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Speakers bureau: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, R. Fleischmann Grant/research support from: Genetech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, Bristol Myers Squibb, Lilly, Sanofi Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, Astra-Zeneca, Jansen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi Aventis, Lexicon, Novartis, Astellas, Astra-Zeneca, Jansen, HGS, J. Wollenhaupt Consultant for: UCB Pharma, A. Deodar Grant/research support from: UCB Pharma, Abbott, Amgen, Janssen, Novartis, Consultant for: UCB Pharma, Abbott, Speakers bureau: Abbott, Novartis, D. Kielar Shareholder of: UCB Pharma, Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, B. Hoepken: None Declared, T. Arledge Shareholder of: UCB Pharma, Employee of: UCB Pharma, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex., Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex., Employee of: Imaging Rheumatology bv

Background Certolizumab pegol (CZP) is a PEGylated humanized Fc-free anti-TNF that is clinically effective in rheumatoid arthritis [1]; this is the first report of clinical efficacy and safety of CZP in psoriatic arthritis (PsA). Objectives To assess efficacy and safety of CZP in patients (pts) with active PsA. Methods Pts with active PsA who had failed ≥1 DMARD and could have failed ≤1 anti-TNF were randomised 1:1:1 to placebo (PBO), or 400mg CZP at week (Wk) 0, 2 and 4 (loading dose, LD) followed by either 200mg CZP Q2W or 400mg CZP Q4W. Pts receiving PBO who failed to achieve a ≥10% decrease in TJC and SJC at both Wks14 and 16 were rescued and randomized at Wk16 to receive CZP 200mg Q2W or CZP 400mg Q4W following LD. The clinical primary endpoint was ACR20 response at Wk12. Non-responder imputation (NRI) was used for ACR and PASI75 responses; last observation carried forward (LOCF) for HAQ. Results 409 pts were randomized. Baseline demographics were similar between the 3 groups; 20% of pts had failed an anti-TNF. ACR20 response at Wk12 was significantly higher in both CZP arms vs PBO (Figure); the majority of the overall response rate observed at Wk24 was achieved by Wk12. Response with CZP was rapid, with a greater ACR20 response as early as Wk1 (7.4% for PBO vs 21.0% for CZP 200mg [p=0.001] and vs 23.0% for CZP 400mg [p<0.001]). At Wks12 and 24, both CZP arms showed significantly greater improvements than PBO in ACR50 and 70 (Figure). Greater improvements were also observed for both CZP arms in PASI75 (Figure), as well as in HAQ-DI at Wk 24 (HAQ-DI change from baseline; -0.50 [CZP combined] vs. -0.19 [PBO], p<0.001). Adverse events (AEs) occurred at the rates of 68% vs. 62% and serious AEs at 4% vs. 7% in PBO vs.CZP (combined dose), respectively. Two deaths occurred, one sudden death of unknown cause (CZP 400mg Q4W) and one myocardial infarct (CZP 200mg Q2W). The safety profile was similar to that observed with CZP in RA. Conclusions CZP effectively improved the signs and symptoms of arthritis, physical function and skin manifestations of psoriasis in pts with PsA with a safety profile similar to what has been observed in RA. References Mease PJ. Rheumatology 2011;50(2):261-70 Disclosure of Interest P. Mease Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, R. Fleischmann Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, A. Deodhar Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, J. Wollenhaupt Consultant for: UCB Pharma, Speakers Bureau: UCB Pharma, D. Kielar Shareholder of: UCB Pharma, Employee of: UCB Pharma, F. Woltering Shareholder of: UCB Pharma, Employee of: UCB Pharma, C. Stach Employee of: UCB Pharma, B. Hoepken Employee of: UCB Pharma, T. Arledge Employee of: UCB Pharma, D. van der Heijde Consultant for: UCB Pharma

Background Axial spondyloarthritis (axSpA) includes both ankylosing spondylitis (AS) and axSpA with no definitive sacroiliitis on X-ray (non-radiographic axSpA, nr-axSpA). RAPID-axSpA (NCT01087762) is the first RCT of an anti-TNF to include both populations. Objectives To report the 24-week (wk) efficacy and assess safety of certolizumab pegol (CZP), a PEGylated Fc-free anti-TNF, in axSpA. Methods The ongoing 158-wk RAPID-axSpA trial was double-blind and placebo (PBO)-controlled to Wk24.1 Recruited pts had adult-onset active axSpA according to the ASAS criteria,2 and included AS pts also meeting the modified New York criteria and nr-axSpA pts. Pts were randomized 1:1:1 to PBO every 2 wks (Q2W), or 400mg CZP at Wk0, 2 and 4 (loading dose) followed by either 200mg CZP Q2W or 400mg CZP every 4 wks (Q4W). The primary endpoint was ASAS20 response at Wk12. Secondary endpoints included ASAS40 and ASAS partial remission responses, and change from baseline (BL) in BASDAI, BASFI, and BASMI linear. Other outcomes included ASDAS major improvement and inactive disease response rates. NRI was used for categorical measures; LOCF was used for continuous measures. Outcomes analyzed in the randomized pt set. Results 325 pts were randomized. BL characteristics were similar between treatment groups. Disease activity was similar between AS and nr-axSpA pts. The primary endpoint, ASAS20 at Wk12, was achieved with clinically and statistically significant improvements in CZP 200mg Q2W and CZP 400mg Q4W arms vs PBO (57.7 and 63.6 vs 38.3, p≤0.004). Significant improvements in ASAS20 were observed as early as Wk1 (40.5 and 34.6 vs 14.0, p<0.001) and maintained at Wk24. Other response rates were also higher in the CZP arms vs PBO at Wk24 (Figure). At Wk24, combined CZP arms showed statistically significant (p<0.001) differences in change from BL vs PBO in BASDAI (-3.1 vs -1.1), BASFI (-2.3 vs -0.4), and BASMI (-0.5 vs -0.1). Similar improvements were reported with CZP vs PBO in both AS and nr-axSpA pts.1 Adverse events (AEs) occurred in 70.4% vs 62.6%, serious AEs in 4.7% vs 4.7%, and serious infections in 1.1% vs 0% of CZP (combined dose) pts vs PBO pts. No deaths or malignancies were reported. Image/graph Conclusions CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed. Similar improvements were observed across CZP dosing regimens, and in both AS and nr-axSpA pts. References Landewé R. Arthritis Rheum 2012;64(10):336-337, Rudwaleit M. Ann Rheum Dis 2009;68(6):770-776 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, Consultant for: Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, Speakers bureau: Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, M. Rudwaleit Consultant for: Abbott, BMS, MSD, Pfizer, Roche, UCB Pharma, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Employee of: Imaging Rheumatology bv, M. Dougados Grant/research support from: UCB Pharma, Consultant for: UCB Pharma, W. Maksymowych Grant/research support from: Abbott, Amgen, BMS, Eli Lilly, Janssen, Merck, Pfizer, Synarc, UCB Pharma, Consultant for: Abbott, Amgen, BMS, Eli Lilly, Janssen, Merck, Pfizer, Synarc, UCB Pharma, Speakers bureau: Abbott, Amgen, BMS, Eli Lilly, Janssen, Merck, Pfizer, Synarc, UCB Pharma, J. Braun Grant/research support from: Abbott, BMS, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma, Consultant for: Abbott, BMS, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma, A. Deodhar Grant/research support from: UCB Pharma, Abbott, Amgen, Janssen, Novartis, Consultant for: UCB Pharma, Abbott, Speakers bureau: Abbott, Novartis, C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, B. Hoepken Shareholder of: UCB Pharma, Employee of: UCB Pharma, G. Coteur: None Declared, D. Kielar Shareholder of: UCB Pharma, Employee of: UCB Pharma, A. Fichtner Employee of: UCB Pharma, T. Arledge Shareholder of: UCB Pharma, Employee of: UCB Pharma, J. Sieper Consultant for: Abbott, Merck, Pfizer, UCB Pharma, Novartis, Lilly, Janssen, Speakers bureau: Abbott, Merck, Pfizer, UCB Pharma, Novartis, Lilly, Janssen

This study investigates the long-term cardiovascular safety of salmeterol powder vs placebo in adolescent and adult patients with mild persistent asthma. Multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Eighteen US clinical centers. Three hundred fifty-two patients (> or = 12 years) with mild persistent asthma (duration > or = 6 months) requiring pharmacotherapy; with FEV1 of 70 to 90% of predicted and without abnormal ECG/continuous ambulatory ECG (Holter). Randomized to twice-daily salmeterol powder (50 microg) or placebo via breath-actuated device for 52 weeks. Backup albuterol was available to control asthma symptoms. Cardiovascular safety was regularly assessed by 12-lead ECG with a 15-s lead II rhythm strip, 24-h continuous ambulatory ECG (Holter) monitoring, serial vital sign measurements, and review of adverse cardiovascular events. No deaths occurred during the study. No clinically significant between-group differences were observed in pulse rate, ECG QTc interval, median number of ventricular or supraventricular ectopic events, incidence of ventricular ectopic couplets and runs, or incidence of > 100 ventricular or supraventricular ectopic events in 24 h. No clinically significant between-group differences were observed in arterial BP or incidence of adverse cardiovascular events. Salmeterol was well tolerated throughout the 52-week study period, with a cardiovascular safety profile similar to that of placebo. Long-term, twice-daily pharmacotherapy with salmeterol powder is safe and is not associated with unfavorable clinically significant changes in cardiac function or increases in cardiovascular adverse effects.