scholarly journals SAT0329 IS THE RATE OF LUNG FUNCTION DECLINE THE SAME IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED ILD (SSC-ILD) WHO EXPERIENCE WEIGHT LOSS? DATA FROM THE SENSCIS TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1110.2-1110
Author(s):  
A. Lescoat ◽  
S. Jouneau ◽  
B. Crestani ◽  
G. Riemekasten ◽  
Y. Kondoh ◽  
...  
Keyword(s):  
Weight Loss ◽  
Placebo Group ◽  
Study Drug ◽  
Annual Rate ◽  
Group Differences ◽  
Lung Function Decline ◽  
Research Support ◽  
Weight Loss Data ◽  
Rate Of Decline ◽  
A Site

Background:In the SENSCIS trial, nintedanib reduced the progression of SSc-ILD vs placebo, as shown by a lower rate of decline in forced vital capacity (FVC). The adverse event (AE) profile of nintedanib was characterised mainly by gastrointestinal (GI) events, including weight loss.Objectives:Assess FVC decline and AEs in subgroups by weight loss ≤5% vs >5% over 52 weeks in the SENSCIS trial.Methods:Patients with SSc-ILD with first non-Raynaud symptom <7 years before screening and ≥10% fibrosis of the lungs on an HRCT scan were randomised to nintedanib or placebo. In a non-randomised comparison, we analysed the rate of decline in FVC (mL/year) and AEs over 52 weeks in subgroups by weight loss (≤5% vs >5%) over 52 weeks.Results:In the nintedanib (n=288) and placebo (n=288) groups, respectively, 112 (38.9%) and 43 (14.9%) patients had weight loss >5% over 52 weeks. At baseline, patients with weight loss >5% over 52 weeks had a higher mean age (57.0 vs 52.9 years), greater proportion of females (81.3% vs 72.9%), and similar mean BMI (26.5 vs 25.7 kg/m2, respectively) and FVC % predicted (71.0% vs 73.1%, respectively) vs patients with weight loss ≤5%. In the placebo group, the mean (SE) annual rate of decline in FVC was similar between patients who had weight loss ≤5% and >5% over 52 weeks (-92.7 [14.7] mL/year and -96.4 [34.9] mL/year, respectively). The estimated annual rate of decline in FVC was lower in patients treated with nintedanib than placebo, with between-group differences in patients who had weight loss ≤5% and >5% of 49.9 mL/year [95% CI 4.2, 95.6]) and 30.2 mL/year [95% CI -50.5, 110.9]), respectively, with no evidence of heterogeneity between subgroups by weight loss (p=0.68 for interaction). Standardised differences in baseline values of potential confounders were <0.2 (indicating negligible differences). The most frequent AEs in patients treated with nintedanib were diarrhoea (74.4% and 77.7% of patients with weight loss ≤5% and >5%, respectively), nausea (30.1% and 33.9%, respectively) and vomiting (19.3% and 33.3%, respectively). In the nintedanib and placebo groups, respectively, AEs leading to discontinuation of study drug occurred in 17.0% and 8.6% of patients with weight loss ≤5%, and 14.3% and 9.3% of patients with weight loss >5% over 52 weeks.Conclusion:In the SENSCIS trial in patients with SSc-ILD, a greater proportion of patients treated with nintedanib than placebo had weight loss >5% over 52 weeks. The rate of decline in FVC was numerically lower in the nintedanib group than in the placebo group both in patients with weight loss ≤5% and >5% over 52 weeks. AEs leading to discontinuation of nintedanib were not more frequent in patients with weight loss >5% vs ≤5%.References:Disclosure of Interests: :Alain LESCOAT: None declared, Stéphane Jouneau Grant/research support from: AIRB, Boehringer Ingelheim, LVL Medical, Novartis, Roche, Bellorophon Therapeutics, Biogen, Fibrogen, Galecto Biotech, Gilead Sciences, Pharm-Olam, Pliant Therapeutics, Savara Pharmaceuticals/Serendex Pharmaceuticals, Consultant of: Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GlazoSmithKline, LVL Medical, Mundipharma, Novartis, Pfizer, Roche, Sanofi, Bruno Crestani Grant/research support from: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Novartis, Roche, Sanofi, Consultant of: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Sanofi, Speakers bureau: AstraZeneca, Boehringer Ingelheim, Roche, Sanofi, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Yasuhiro Kondoh Consultant of: Boehringer Ingelheim, Asahi Kasei Pharma, Janssen, Shionogi, Speakers bureau: Boehringer Ingelheim, Asahi Kasei Pharma, Janssen, Eisai, KYORIN, Mitsubishi Tanabe Pharma, Novartis, Shionogi, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Nina Patel Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Speakers bureau: Genentech, John Huggins Consultant of: I was a site PI for the SENSCIS trial for Boehringer Ingelheim, Christian Stock Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer

THU0330 EFFECTS OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED ILD (SSC-ILD) AND DIFFERING EXTENTS OF SKIN FIBROSIS: FURTHER ANALYSES OF THE SENSCIS TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 395-396
Author(s):  
Y. Allanore ◽  
V. Steen ◽  
M. Kuwana ◽  
C. Denton ◽  
M. Matucci-Cerinic ◽  
...  
Keyword(s):  
Placebo Group ◽  
Systemic Sclerosis ◽  
Topoisomerase I ◽  
Statistical Testing ◽  
Skin Fibrosis ◽  
Annual Rate ◽  
Research Support ◽  
High Resolution Computed Tomography ◽  
Significant Difference ◽  
Rate Of Decline

Background:In the SENSCIS trial, nintedanib reduced the progression of SSc-ILD compared with placebo, as shown by a significantly lower rate of decline in forced vital capacity (FVC) over 52 weeks. There was no significant difference between treatment groups in change in modified Rodnan skin score (mRSS) at week 52. An mRSS of 18–25 has been proposed as an upper cut-off to enrich a cohort for skin-progressive patients. Progression of skin fibrosis has been associated with later progression of ILD.Objectives:To assess the effects of nintedanib on the rate of FVC decline and change in mRSS in the SENSCIS trial in subgroups by mRSS <18 and ≥18 at baseline.Methods:Patients with SSc-ILD with onset of first non-Raynaud symptom <7 years before screening and ≥10% fibrosis of the lungs on a high-resolution computed tomography scan were randomised to receive nintedanib or placebo. We analysed the rate of decline in FVC (ml/year) over 52 weeks and the change from baseline in mRSS at week 52 in subgroups by mRSS (<18; ≥18) at baseline.Results:In the nintedanib and placebo groups, respectively, 219/288 (76.0%) and 226/288 (78.5%) patients had mRSS <18 at baseline. Compared with those with mRSS <18, patients with mRSS ≥18 had a lower mean FVC % predicted (68.3% vs 73.7%) and greater proportions were taking mycophenolate at baseline (58.1% vs 45.6%), were anti-topoisomerase I antibody positive (67.4% vs 58.7%) and had diffuse cutaneous SSc (100% vs 37.8%). The mean (SE) annual rate of decline in FVC in the placebo group was numerically greater in patients who had mRSS ≥18 than mRSS <18 at baseline (-131.7 [29.2] mL/year vs -81.4 [15.4] mL/year). The effect of nintedanib vs placebo on reducing the annual rate of decline in FVC was numerically more pronounced in patients with mRSS ≥18 (difference: 88.7 mL/year [95% CI 7.7, 169.8]) than mRSS <18 (difference: 26.4 mL/year (95% CI -16.8, 69.6) at baseline, but statistical testing did not indicate heterogeneity in the treatment effect of nintedanib between subgroups (p=0.18 for treatment-by-time-by-subgroup interaction) (Figure). In the nintedanib and placebo groups, respectively, changes in mRSS at week 52 were -2.2 (0.3) and -2.1 (0.3) (difference -0.1 [95% CI -1.0, 0.7]) in patients with mRSS <18 at baseline and -2.1 (0.7) and -1.6 (0.7) (difference -0.6 [95% CI -2.1, 1.0]) in patients with mRSS ≥18 at baseline (p=0.62 for treatment-by-visit-by-subgroup interaction).Conclusion:In the placebo group of the SENSCIS trial, the rate of decline in FVC over 52 weeks was numerically greater in patients with mRSS ≥18 than <18 at baseline, while reductions in mRSS were similar. A lower rate of FVC decline was observed in patients treated with nintedanib than placebo both in patients with mRSS ≥18 and <18 at baseline.Acknowledgments:The SENSCIS trial was funded by Boehringer IngelheimDisclosure of Interests:Yannick Allanore Grant/research support from: Yannick Allanore has received grants from Inventiva, Roche and Sanofi, Consultant of: Yannick Allanore has received fees from Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Curzion, Inventiva, Roche, Sanofi, Viginia Steen Grant/research support from: The associated affiliation has received grants/research from Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, Eicos, Galapagos, Immune Tolerance Network, Reata, Consultant of: Virginia Steen has acted as a consultant for Boehringer Ingelheim, Corbus, CSL Behring, Eicos, Forbius, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Elizabeth Volkmann Grant/research support from: Forbius, Corbus Pharmaceuticals, Consultant of: Boehringer Ingelheim, Forbius, Speakers bureau: Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB, Daniel Wachtlin Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Manuel Quaresma Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

SAT0345 IS THERE A DIFFERENCE BETWEEN THE SEXES IN THE RATE OF PROGRESSION OF SYSTEMIC SCLEROSIS-ASSOCIATED ILD (SSC-ILD)? DATA FROM THE SENSCIS TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1118-1119
Author(s):  
E. Volkmann ◽  
S. Vettori ◽  
J. Varga ◽  
A. Herrick ◽  
M. Cutolo ◽  
...  
Keyword(s):  
Placebo Group ◽  
Adverse Events ◽  
Trial Steering Committee ◽  
Annual Rate ◽  
P Value ◽  
Research Support ◽  
Serious Adverse Events ◽  
Female Patients ◽  
Males And Females ◽  
Rate Of Decline

Background:Previous studies suggested that male sex may be associated with a greater rate of decline in FVC in patients with SSc-ILD. In the SENSCIS trial, nintedanib reduced the rate of FVC decline over 52 weeks vs placebo.Objectives:Analyse the rate of decline in FVC and the efficacy and safety of nintedanib in the SENSCIS trial in subgroups by sex.Methods:Patients with SSc-ILD with first non-Raynaud symptom <7 years before screening and ≥10% fibrosis of the lungs on HRCT were randomised to nintedanib or placebo. We analysed the rate of decline in FVC (mL/year) and adverse events over 52 weeks in male and female patients.Results:Of 576 patients, 433 (75.2%) were female. Compared with males, the female subgroup included a smaller proportion of White patients (64.7% vs 74.8%), a smaller proportion on mycophenolate at baseline (46.9% vs 53.1%), a greater proportion of ATA positive patients (63.3% vs 53.1%), and had a lower mean weight at baseline (66.6 vs 79.1 kg). FVC % predicted (72.8% vs 71.7%) and mRSS (11.2 vs 10.8) were similar in females and males. The adjusted annual rate of decline in FVC in the placebo group was numerically greater in male than female patients (-126.8 [SE 29.0] vs -82.0 [16.2] mL/year). The estimated effect of nintedanib vs placebo on reducing the rate of decline in FVC was numerically more pronounced in males than females (difference: 58.6 [95% CI -18.0, 135.1] vs 34.6 [-9.3, 78.4] mL/year), but the interaction p-value did not indicate heterogeneity in the treatment effect between subgroups (p=0.59). Among nintedanib-treated patients, diarrhoea was reported in similar proportions of females and males (74.7% vs 79.1%); nausea, vomiting and liver test abnormalities were reported in greater proportions of females vs males (35.3% vs 19.4%, 28.1% vs 13.4%, and 15.4% vs 9.0%), while serious adverse events were more frequent in males (32.8% vs 21.3%). In the nintedanib and placebo groups, respectively, adverse events leading to treatment discontinuation were reported in 16.7% and 8.5% of females and 13.4% and 9.2% of males.Conclusion:In the SENSCIS trial in patients with SSc-ILD, the annual rate of decline in FVC in the placebo group was numerically greater in male than female patients. The rate of FVC decline was lower with nintedanib than placebo both in males and females. The safety profile of nintedanib was similar between males and females.Disclosure of Interests:Elizabeth Volkmann Grant/research support from: Forbius, Corbus Pharmaceuticals, Consultant of: Boehringer Ingelheim, Forbius, Speakers bureau: Boehringer Ingelheim, Serena Vettori Consultant of: Boehringer Ingelheim, John Varga Grant/research support from: John Varga is awaiting grants from Boehringer Ingelheim and has received grants from Bristol-Myers Squibb, Pfizer, Takeda, and TeneoBio, Consultant of: John Varga has acted as a consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Emerald Health, and TeneoBio, Ariane Herrick: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Ana Cordeiro Consultant of: Ana Cordeiro has acted as a consultant for Roche, Speakers bureau: Ana Cordeiro has received speaker fees from Boehringer Ingelheim, Lilly, and Vitoria, Valderilio F Azevedo Grant/research support from: Abbvie, Janssen, Bristol-Myers Squibb, Boehringer-Ingelheim, Lilly and Novartis, Consultant of: Lilly, Novartis, Janssen, Boehringer-Ingelheim, Amgen, Pfizer and Abbvie, Speakers bureau: Sandoz, Celltrion, Lilly, Novartis, Janssen, Boehringer-Ingelheim, Amgen, Pfizer and Abbvie, Sindhu Johnson Grant/research support from: Boehringer Ingelheim, Corbus Pharmaceuticals, GlaxoSmithKline, Roche, Merck, Bayer, Consultant of: Boehringer Ingelheim, Ikaria, Christian Stock Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Lizette Moros Employee of: Lizette Moros is an employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Maureen Mayes Grant/research support from: Maureen Mayes has received grants from Boehringer Ingelheim, Corbus, CSL Behring, Eicos, and Galapagos, Consultant of: Maureen Mayes has acted as a consultant for Boehringer Ingelheim, Eicos, and Galapagos. She was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim)

scholarly journals OP0170 DECLINE IN FORCED VITAL CAPACITY (FVC) IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSC-ILD) WITH AND WITHOUT DYSPNOEA: DATA FROM THE SENSCIS TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 101.2-102
Author(s):  
E. Volkmann ◽  
M. Kreuter ◽  
A. M. Hoffmann-Vold ◽  
M. Wijsenbeek ◽  
V. Smith ◽  
...  
Keyword(s):  
Placebo Group ◽  
Lung Disease ◽  
Treatment Effect ◽  
Medical Officer ◽  
International Committee ◽  
Response To Therapy ◽  
P Value ◽  
Research Support ◽  
Patient Reported ◽  
Rate Of Decline

Background:Some patients with SSc-ILD develop dyspnoea secondary to parenchymal lung disease, while others do not report dyspnoea even when their lung function is impaired. It is unclear whether the presence of dyspnoea is associated with a worse course of SSc-ILD or with response to therapy.Objectives:To investigate the rate of decline in FVC in patients with SSc-ILD in the SENSCIS trial in subgroups by patient-reported dyspnoea at baseline.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom within ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in patients with and without dyspnoea at baseline based on the question about dyspnoea in the St. George’s Respiratory Questionnaire (SGRQ). Patients who reported having shortness of breath “most days a week”, “several days a week” or “a few days a month” (rather than “only with chest infection” or “not at all”) over the last month were considered to have dyspnoea at baseline. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test was applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.Results:Of 576 patients, 69.8% had dyspnoea at baseline. At baseline, in patients with and without dyspnoea, respectively, mean (SD) extent of fibrotic ILD on HRCT was 37.7 (21.7)% and 31.6 (19.4)%; mean (SD) FVC was 71.0 (16.3) and 76.5 (16.8) % predicted; 50.7% and 44.8% were taking mycophenolate; 53.5% and 41.9% were taking corticosteroids. In the placebo group, the rate of decline in FVC (mL/year) was similar in patients with and without dyspnoea at baseline (Figure). The effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) was numerically more pronounced in patients without dyspnoea (difference: 79.8 [95% CI: 9.8, 149.7]) than with dyspnoea (difference: 25.7 [-19.9, 71.3]), but the exploratory interaction p-value did not indicate heterogeneity in the treatment effect between subgroups (p=0.20).Conclusion:In the SENSCIS trial, patients with SSc-ILD who had dyspnoea at baseline had a numerically greater extent of fibrotic ILD on HRCT and numerically lower FVC % predicted at baseline. The rate of decline in FVC in the placebo group was similar in patients with and without dyspnoea. Nintedanib had a numerically greater treatment effect in patients without dyspnoea. These data suggest that the presence of dyspnoea should not be used as a criterion for starting nintedanib in patients with SSc-ILD.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by Fleishman Hillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Michael Kreuter Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim and Roche, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme and Roche, Consultant of: Actelion, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Marlies Wijsenbeek Speakers bureau: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Consultant of: Boehringer Ingelheim (fees paid to institution), Bristol-Myers Squibb (fees paid to institution), Galapagos NV (fees paid to institution), Hoffmann-La Roche (fees paid to institution), NeRRe Therapeutics (fees paid to institution), OncoArendi Therapeutics (fees paid to institution), Respivant Sciences (fees paid to institution) and Savara (fees paid to institution), Grant/research support from: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen-Cilag NV, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Janssen-Cilag NV and Research Foundation - Flanders (FWO), Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc., Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Wim Wuyts: None declared, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Steven Sambevski Employee of: Currently an employee of Boehringer Ingelheim, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals

THU0363 EFFECTS OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED ILD (SSC-ILD) AND NORMAL VERSUS ELEVATED C-REACTIVE PROTEIN (CRP) AT BASELINE: ANALYSES FROM THE SENSCIS TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 413-414
Author(s):  
G. Riemekasten ◽  
P. Carreira ◽  
L. A. Saketkoo ◽  
M. Aringer ◽  
L. Chung ◽  
...  
Keyword(s):  
Placebo Group ◽  
High Sensitivity ◽  
Similar Proportion ◽  
P Value ◽  
Research Support ◽  
Absolute Increase ◽  
Reactive Protein ◽  
Inflammatory Phenotype ◽  
Rate Of Decline ◽  
To Receive

Background:In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks. Elevated CRP is a marker of an inflammatory phenotype and has been associated with a greater rate of decline in FVC and higher mortality in patients with SSc.Objectives:To assess the effects of nintedanib in subgroups by CRP at baseline in the SENSCIS trial.Methods:Patients with SSc-ILD with onset of first non-Raynaud symptom <7 years and ≥10% fibrosis of the lungs on HRCT were randomised to receive nintedanib or placebo. We analysed the rate of decline in FVC (mL/year) over 52 weeks, the proportion of patients with an absolute increase in FVC ≥3% predicted (proposed as the minimal clinically important difference for improvement in FVC in patients with SSc-ILD), and absolute change from baseline in mRSS at week 52 in subgroups with normal vs elevated high-sensitivity CRP (≤4.99 vs >4.99 mg/L) at baseline.Results:Of patients with available data, 78/270 (28.9%) and 74/261 (28.4%) in the nintedanib and placebo groups, respectively, had CRP >4.99 mg/L at baseline. Compared with patients with lower CRP, those with CRP >4.99 mg/L included a similar proportion of patients who were ATA-positive (61.8% vs 60.2%, respectively), a greater proportion with diffuse cutaneous SSc (63.2% vs 49.3%) and had a higher mean mRSS (13.7 vs 10.2) and lower mean FVC % predicted (68.6% vs 73.9%). The adjusted annual rate of decline in FVC in the placebo group was numerically greater in patients with CRP >4.99 than ≤4.99 mg/L at baseline (-106.6 [SE 27.6] vs -83.0 [17.1] mL/year). The effect of nintedanib vs placebo on reducing the rate of decline in FVC was numerically more pronounced in patients with CRP >4.99 than ≤4.99 mg/L at baseline but the treatment-by-time-by-subgroup interaction p-value did not indicate heterogeneity in the effect of nintedanib between subgroups (p=0.70) (Figure). In the nintedanib and placebo groups, respectively, the proportions of patients with an absolute increase in FVC ≥3% predicted at week 52 were 20.4% and 15.0% in those with CRP ≤4.99 mg/L and 24.4% and 14.9% in those with CRP >4.99 mg/L at baseline (treatment-by-subgroup interaction p=0.59); adjusted mean changes in mRSS at week 52 were -2.2 (SE 0.3) and -2.1 (0.3) in those with CRP ≤4.99 mg/L (difference -0.1 [95% CI -1.0, 0.8]) and -2.3 (0.5) and -1.0 (0.5) in those with CRP >4.99 mg/L at baseline (difference -1.2 [-2.7, 0.2]; treatment-by-visit-by-subgroup interaction p=0.20).Conclusion:In the SENSCIS trial, the rate of decline in FVC over 52 weeks in the placebo group was numerically greater in patients with elevated CRP at baseline. Nintedanib reduced the rate of decline in FVC both in patients with normal and elevated CRP at baseline, with a numerically greater effect in patients with elevated CRP.Disclosure of Interests:Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Lesley Ann Saketkoo Grant/research support from: Corbus Pharmaceuticals, United Therapeutics, Consultant of: Boehringer Ingelheim, Eicos Sciences, Speakers bureau: Boehringer Ingelheim, Martin Aringer Consultant of: Boehringer Ingelheim, Roche, Speakers bureau: Boehringer Ingelheim, Roche, Lorinda Chung Grant/research support from: United Therapeutics, Boehringer Ingelheim, Consultant of: Bristol-Myers Squibb, Boehringer Ingelheim, Mitsubishi Tanabe, Eicos Sciences, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Corinna Miede Employee of: Employee of Boehringer Ingelheim, Susanne Stowasser Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB

scholarly journals OP0124 EFFECTS OF NINTEDANIB IN PATIENTS WITH PROGRESSIVE FIBROSING INTERSTITIAL LUNG DISEASE ASSOCIATED WITH RHEUMATOID ARTHRITIS (RA-ILD) IN THE INBUILD TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 69.2-69
Author(s):  
C. Kelly ◽  
E. Matteson ◽  
M. Aringer ◽  
G. R. Burmester ◽  
H. Mueller ◽  
...  
Keyword(s):  
Placebo Group ◽  
Adverse Events ◽  
Usual Interstitial Pneumonia ◽  
Group Versus ◽  
International Committee ◽  
Common Adverse Event ◽  
Research Support ◽  
High Resolution Computed Tomography ◽  
Biologic Dmards ◽  
Rate Of Decline

Background:In the INBUILD trial in subjects with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF), nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks by 57% compared with placebo.Objectives:To assess the rate of decline in FVC in subjects with RA-ILD in the INBUILD trial.Methods:Subjects in the INBUILD trial had a chronic fibrosing ILD other than IPF, reticular abnormality with traction bronchiectasis (with or without honeycombing) of >10% extent on high-resolution computed tomography (HRCT), forced vital capacity (FVC) ≥45% predicted, diffusing capacity of the lungs for carbon monoxide ≥30%–<80% predicted, and met criteria for progression of ILD within the 24 months before screening, despite management deemed appropriate in clinical practice. Patients taking stable doses of approved medications to treat RA or connective tissue disease could participate, except that the protocol excluded those taking azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, rituximab, cyclophosphamide, or oral glucocorticoids >20 mg/day. We analysed the rate of decline in FVC (mL/year) over 52 weeks and adverse events in subjects with RA-ILD.Results:Of 663 subjects who received trial medication, 89 had RA-ILD (42 nintedanib, 47 placebo), of whom 60.7% were male, 64.0% were current or former smokers, 86.5% had a usual interstitial pneumonia (UIP)-like pattern on HRCT; 93.3% had received confirmation of their RA diagnosis from a rheumatologist. At baseline, 21.3% of subjects were taking biologic disease-modifying anti-rheumatic drugs (DMARDs), 53.9% were taking non-biologic DMARDs and 73.0% were taking glucocorticoids (≤20 mg/day prednisone or equivalent). At baseline, mean (SD) age was 66.9 (9.6) years, time since RA diagnosis was 9.9 (9.4) years, time since ILD diagnosis was 3.6 (3.2) years, FVC was 71.5 (16.2) % predicted and C-reactive protein was 13.7 (22.5) mg/L. The adjusted mean (SE) rate of decline in FVC over 52 weeks was -82.6 (41.3) mL/year in the nintedanib group versus -199.3 (36.2) mL/year in the placebo group (difference 116.7 mL/year [95% CI 7.4, 226.1]; nominal p=0.037), consistent with findings in the overall trial population (Figure). As in the overall trial population, the most common adverse event in subjects with RA-ILD was diarrhoea (reported in 54.8% of the nintedanib group and 25.5% of the placebo group). Adverse events led to permanent discontinuation of trial drug in 19.0% of subjects in the nintedanib group and 12.8% of subjects in the placebo group.Conclusion:In the INBUILD trial, nintedanib slowed the rate of decline in FVC in patients with progressive fibrosing RA-ILD, with adverse events that were manageable for most patients. The efficacy and safety of nintedanib in subjects with RA-ILD were consistent with those observed in the overall trial population.Acknowledgements:The INBUILD trial was funded by Boehringer Ingelheim. Medical writing support was provided by Fleishman Hillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Clive Kelly Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Eric Matteson Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim and Gilead Sciences, Grant/research support from: Sun Pharmaceuticals and Pfizer, Martin Aringer Speakers bureau: AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Gilead, GlaxoSmithKline, HEXAL, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and UCB, Consultant of: AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi and UCB, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Lilly, Merck Sharp & Dohme, Pfizer, Roche and Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Lilly, Merck Sharp & Dohme, Pfizer, Roche and Sanofi, Heiko Mueller Employee of: Currently an employee of Boehringer Ingelheim, Lizette Moros Employee of: Currently an employee of Boehringer Ingelheim, Klaus Rohr Employee of: Currently an employee of Boehringer Ingelheim, Martin Kolb Consultant of: Algernon, Boehringer Ingelheim, Pieris Pharmaceuticals and Roche, Grant/research support from: Boehringer Ingelheim, Pieris Pharmaceuticals and Prometic

Exploration-Stage Implementation Variation

2014 ◽  
Vol 222 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Stephanie Romney ◽  
Nathaniel Israel ◽  
Danijela Zlatevski
Keyword(s):  
Parent Training ◽  
Average Cost ◽  
Cost Savings ◽  
Training Group ◽  
Group Differences ◽  
Triple P ◽  
Community Based ◽  
Parent Training Program ◽  
A Site ◽  
The Cost

The present study examines the effect of agency-level implementation variation on the cost-effectiveness of an evidence-based parent training program (Positive Parenting Program: “Triple P”). Staff from six community-based agencies participated in a five-day training to prepare them to deliver a 12-week Triple P parent training group to caregivers. Prior to the training, administrators and staff from four of the agencies completed a site readiness process intended to prepare them for the implementation demands of successfully delivering the group, while the other two agencies did not complete the process. Following the delivery of each agency’s first Triple P group, the graduation rate and average cost per class graduate were calculated. The average cost-per-graduate was over seven times higher for the two agencies that had not completed the readiness process than for the four completing agencies ($7,811 vs. $1,052). The contrast in costs was due to high participant attrition in the Triple P groups delivered by the two agencies that did not complete the readiness process. The odds of Triple P participants graduating were 12.2 times greater for those in groups run by sites that had completed the readiness process. This differential attrition was not accounted for by between-group differences in participant characteristics at pretest. While the natural design of this study limits the ability to empirically test all alternative explanations, these findings indicate a striking cost savings for sites completing the readiness process and support the thoughtful application of readiness procedures in the early stages of an implementation initiative.

scholarly journals AB1059 A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ANAKINRA IN PATIENTS WITH STILL´S DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1819.2-1820
Author(s):  
L. Schanberg ◽  
P. Nigrovic ◽  
A. Cooper ◽  
W. Chatham ◽  
S. Akoghlanian ◽  
...  
Keyword(s):  
Early Onset ◽  
Disease Onset ◽  
Study Drug ◽  
Placebo Patient ◽  
Controlled Study ◽  
Symptom Duration ◽  
Newly Diagnosed ◽  
Still’S Disease ◽  
Research Support ◽  
Still's Disease

Background:Adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) are rare autoinflammatory disorders associated with an activated IL-1 pathway, characterized by spiking fever, rash, arthritis, lymphadenopathy, hepatosplenomegaly and serositis. There is a growing understanding that SJIA and AOSD are one disease with different ages of onset, i.e. Still’s disease. The anaSTILLs study (anakinra inStill´sdisease) was designed to further evaluate efficacy and safety of anakinra in patients with Still´s disease across all age groups.Objectives:The primary objective was to demonstrate efficacy of anakinra versus placebo as assessed by ACR30 response with absence of fever at Week 2. Secondary objectives included: early onset of efficacy, sustained efficacy, time to study drug discontinuation, safety, pharmacokinetics, clinical signs and biomarkers.Methods:‘anaSTILLs’ was a randomized, double-blind, placebo-controlled, 12-week study including patients with active and newly diagnosed (6 months) Still´s disease according to adapted ILAR criteria if <16, or Yamaguchi criteria, if ≥16 years of age at disease onset. Patients were randomized to anakinra 2 mg/kg (max 100 mg/day), 4 mg/kg (max 200 mg/day) or placebo.Results:12 patients were randomized and received study drug: 6 anakinra (2 mg/kg n=2, 4 mg/kg n=4) and 6 placebo, the study was terminated early due to slow recruitment. 1 patient on placebo had lymphoma, not Still’s disease, and was excluded; thus in total 11 patients were analyzed for efficacy, 8 were children [median (range) age=4.0 (1-11) years] and 3 were adults [median (range) age=32.0 (25-51) years]. 55% were male and the mean symptom duration was 74.2 days. All patients on anakinra but none on placebo achieved ACR30 response with absence of fever at Week 2 (p-value=0.0022). The efficacy of anakinra was further demonstrated by superiority to placebo in ACR50/70/90 responses with absence of fever at Week 2. All placebo patients discontinued the study within 6 weeks, 2 due to progressive disease, 2 due to lack of efficacy and 1 due to withdrawal by patient. There was a numerically higher proportion with early onset of efficacy (Week 1) in the anakinra group compared to placebo. The ACR30/50/70/90 responses in the anakinra group were sustained throughout the study period. Patients in the anakinra group had a prompt and persistent decrease in CRP and ferritin levels at Week 1, which was not observed in the placebo group. There were no unexpected safety findings. All anakinra patients developed anti-drug antibodies (ADAs) at some timepoint during the study. ADAs were persistent throughout the treatment period, except in one patient. Titers were low to moderate. One placebo patient had low ADA titers at one occasion. No neutralizing antibodies were observed and the ADAs did not appear to impact clinical efficacy or safety.Conclusion:Anakinra is superior to placebo in the treatment of Still’s disease. ADAs occur frequently but do not appear to adversely impact efficacy or safety. These results confirm the benefits of anakinra treatment in patients with active, newly diagnosed Still´s disease across ages.Disclosure of Interests:Laura Schanberg Grant/research support from: Sobi, BMS, Consultant of: Aurinia, UCB, Sanofi, Peter Nigrovic Grant/research support from: Novartis, BMS, Pfizer, Consultant of: Novartis, BMS, Pfizer, Sobi, Miach Orthopedics, Simcere, XBiotech, Quench Bio, Ashley Cooper: None declared, Winn Chatham Grant/research support from: Sobi, Consultant of: Sobi, Shoghik Akoghlanian: None declared, Namrata Singh: None declared, Egla Rabinovich Grant/research support from: AbbVie, UCB Pharma, Janssen Research & Development, Akaluck Thatayatikom: None declared, Alysha Taxter: None declared, Jonathan Hausmann Consultant of: Novartis, Milan Zdravkovic Shareholder of: Sobi, Employee of: Sobi, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Henrik Andersson Employee of: Sobi, Susanna Cederholm Shareholder of: Sobi, Employee of: Sobi, Margareta Wikén Shareholder of: Sobi, Employee of: Former employee of Sobi, Rayfel Schneider Grant/research support from: Roche, Novartis, Sobi, Pfizer, Consultant of: Sobi, Novartis, Novimmune, Fabrizio De Benedetti Grant/research support from: AbbVie, Pfizer, Novartis, Novimmune, Sobi, Sanofi, Roche, Speakers bureau: AbbVie, Novartis, Roche, Sobi

scholarly journals The Effect of Protein Supplementation versus Carbohydrate Supplementation on Muscle Damage Markers and Soreness Following a 15-km Road Race: A Double-Blind Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 858
Author(s):  
Dominique S. M. ten Haaf ◽  
Martin A. Flipsen ◽  
Astrid M. H. Horstman ◽  
Hans Timmerman ◽  
Monique A. H. Steegers ◽  
...  
Keyword(s):  
Placebo Group ◽  
Protein Intake ◽  
Muscle Soreness ◽  
Controlled Trial ◽  
Protein Supplementation ◽  
Group Differences ◽  
Double Blind ◽  
Carbohydrate Supplementation ◽  
Protein Group ◽  
Road Race

We assessed whether a protein supplementation protocol could attenuate running-induced muscle soreness and other muscle damage markers compared to iso-caloric placebo supplementation. A double-blind randomized controlled trial was performed among 323 recreational runners (age 44 ± 11 years, 56% men) participating in a 15-km road race. Participants received milk protein or carbohydrate supplementation, for three consecutive days post-race. Habitual protein intake was assessed using 24 h recalls. Race characteristics were determined and muscle soreness was assessed with the Brief Pain Inventory at baseline and 1–3 days post-race. In a subgroup (n = 149) muscle soreness was measured with a strain gauge algometer and creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations were measured. At baseline, no group-differences were observed for habitual protein intake (protein group: 79.9 ± 26.5 g/d versus placebo group: 82.0 ± 26.8 g/d, p = 0.49) and muscle soreness (protein: 0.45 ± 1.08 versus placebo: 0.44 ± 1.14, p = 0.96). Subjects completed the race with a running speed of 12 ± 2 km/h. With the Intention-to-Treat analysis no between-group differences were observed in reported muscle soreness. With the per-protocol analysis, however, the protein group reported higher muscle soreness 24 h post-race compared to the placebo group (2.96 ± 2.27 versus 2.46 ± 2.38, p = 0.039) and a lower pressure muscle pain threshold in the protein group compared to the placebo group (71.8 ± 30.0 N versus 83.9 ± 27.9 N, p = 0.019). No differences were found in concentrations of CK and LDH post-race between groups. Post-exercise protein supplementation is not more preferable than carbohydrate supplementation to reduce muscle soreness or other damage markers in recreational athletes with mostly a sufficient baseline protein intake running a 15-km road race.

scholarly journals OP0172 EFFECT OF WEIGHT LOSS AND LIRAGLUTIDE ON SERUM URATE LEVELS AMONG OBESE KNEE OSTEOARTHRITIS PATIENTS: SECONDARY ANALYSIS OF A RANDOMISED CONTROLLED TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 107.1-108
Author(s):  
K. Zobbe ◽  
S. M. Nielsen ◽  
R. Christensen ◽  
A. Overgaard ◽  
H. Gudbergsen ◽  
...  
Keyword(s):  
Weight Loss ◽  
Knee Osteoarthritis ◽  
Secondary Analysis ◽  
Serum Urate ◽  
Advisory Board ◽  
Research Support ◽  
Blood Samples ◽  
Diet Intervention ◽  
Lowering Drug ◽  
The Impact

Background:There is a strong association between gout and obesity. Lowering urate is the cornerstone of gout management [1] and urate levels correlate strongly with central obesity. Previous studies suggest that weight loss has a positive effect on serum urate, however, the studies are sparse and small [2].Objectives:To assess the impact of an initial low-calorie diet-induced weight loss and subsequent randomisation to the body weight-lowering drug liraglutide (a glucagon-like peptide 1 receptor agonist) or placebo on serum urate levels.Methods:In the LOSE-IT trial (NCT02905864), a randomised, double-blinded, placebo-controlled, parallel group, single-centre trial [3], 156 obese individuals with knee osteoarthritis, but without gout, were offered an initial 8-week intensive diet intervention (week -8 to 0) on Cambridge Weight Plan (800-1000 kcal/day) followed by a weight loss maintenance period in which participants were randomised to either liraglutide 3 mg/day or placebo for 52 weeks. We conducted a secondary analysis of blood samples collected at week -8, 0 and 52. The primary outcome measure was change in serum urate. We used paired t-test for the change from week -8 to 0, and for change from week 0 to 52 we used an ANCOVA model adjusted for stratification factors (sex, age category and obesity class), and the level of the outcome at baseline. Data were analysed as observed (i.e. no imputation of missing data).Results:156 individuals were randomised and 155 had blood samples taken at baseline. In the initial intensive diet intervention period (week -8 to 0) they lost a mean of 12.5 kg (95% CI -13.1 to -11.9, n 156). In the following 52 weeks, the liraglutide group lost an additional 4.1 kg (SE 1.2, n 71) whereas the control group was almost unchanged with a weight loss of 0.2 kg (SE 1.2, n 66). Looking at the main outcome of serum urate levels change, the initial intensive diet resulted in a mean decrease of 0.21 mg/dL (95% CI 0.35 to 0.07, n 155) for the entire cohort. In the following year (week 0 to 52) the liraglutide group exhibited a further mean decrease in serum urate of 0.48 mg/dL (SE 0.11, n 69), whereas the placebo group exhibited a slight decrease in mean serum urate of 0.07 mg/dL (SE 0.12, n 65) resulting in a significant between-group difference of -0.40 mg/dL (95% CI -0.69 to -0.12, n 134) – see Figure 1. Four participants in each group experienced serious adverse events; no deaths were observed.Conclusion:This secondary analysis of the LOSE-IT trial suggests that liraglutide provides a potential novel serum urate lowering drug mechanism in obese patient populations, with potential implication for gout treatment.References:[1]Richette P et al. 2016.Ann Rheum Dis2017;76:29–42.[2]Nielsen SM et al.Ann Rheum Dis2017 76(11):1870-1882.[3]Gudbergsen H et al.BMJ2019. 71–2.Disclosure of Interests:Kristian Zobbe: None declared, Sabrina Mai Nielsen: None declared, Robin Christensen: None declared, Anders Overgaard: None declared, henrik gudbergsen Speakers bureau: Pfizer 2016, Marius Henriksen: None declared, Henning Bliddal Grant/research support from: received research grant fra NOVO Nordic, Consultant of: consultant fee fra NOVO Nordic, Lene Dreyer: None declared, Lisa Stamp: None declared, Filip Krag Knop Shareholder of: Minority shareholder in Antag Therapeutics Aps, Grant/research support from: AstraZeneca, Gubra, Novo Nordisk, Sanofi and Zealand Pharma, Consultant of: Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, MSD/Merck, Mundipharma, Novo Nordisk, Sanofi and Zealand Pharma., Speakers bureau: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi and Zealand Pharma., Lars Erik Kristensen Consultant of: UCB Pharma (Advisory Board), Sannofi (Advisory Board), Abbvie (Advisory Board), Biogen (Advisory Board), Speakers bureau: AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Forward Pharma, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, and UCB Pharma

Meta-analysis of the age-associated decline in maximal aerobic capacity in men: relation to training status

2000 ◽  
Vol 278 (3) ◽  
pp. H829-H834 ◽  
Author(s):  
Teresa M. Wilson ◽  
Hirofumi Tanaka
Keyword(s):  
Meta Analysis ◽  
Maximal Oxygen Consumption ◽  
Group Differences ◽  
Maximal Heart Rate ◽  
Maximal Aerobic Capacity ◽  
Cross Sectional ◽  
Physically Active ◽  
Age Related ◽  
Rate Of Decline ◽  
Exercise Status

Based on cross-sectional data, we recently reported that, in contrast to the prevailing view, the rate of decline in maximal oxygen consumption (V˙o 2 max) with age is greater in physically active compared with sedentary healthy women. We tested this hypothesis in men using a meta-analytic study ofV˙o 2 max values in the published literature. A total of 242 studies (538 subject groups and 13,828 subjects) met the inclusion criteria and were arbitrarily separated into sedentary (214 groups, 6,231 subjects), active (159 groups, 5,621 subjects), and endurance-trained (165 groups, 1,976 subjects) populations. Body fat percent increased with age in sedentary and active men ( P < 0.001), whereas no change was observed in endurance-trained men.V˙o 2 max was inversely and strongly related to age within each population ( r = −0.80 to −0.88, all P < 0.001) and was highest in endurance-trained and lowest in sedentary populations at any age. Absolute rates of decline inV˙o 2 max with age were not different ( P > 0.05) in sedentary (−4.0 ml ⋅ kg−1 ⋅ min−1 ⋅ decade−1), active (−4.0), and endurance-trained (−4.6) populations. Similarly, there were no group differences ( P > 0.05) in the relative (%) rates of decline inV˙o 2 max with advancing age (−8.7, −7.3, and −6.8%/decade, respectively). Maximal heart rate was inversely related to age within each population ( r = −0.88 to −0.93, all P < 0.001), but the rate of age-related reduction was not different among the populations. There was a significant decline in running mileage and speed with advancing age in the endurance-trained men. The present cross-sectional meta-analytic findings do not support the hypothesis that the rate of decline inV˙o 2 max with age is related to habitual aerobic exercise status in men.

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