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

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

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 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

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

scholarly journals AB1335-HPR HEALTH PROFESSIONALS’ PERSPECTIVE ON THE BENEFITS AND RISKS OF LOW-DOSE GLUCOCORTICOIDS IN RHEUMATOID ARTHRITIS – AN INTERNATIONAL SURVEY OF 444 HEALTH PROFESSIONALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1955.1-1956
Author(s):  
T. Santiago ◽  
M. Voshaar ◽  
M. De Wit ◽  
P. Carvalho ◽  
M. Boers ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Professionals ◽  
Patient Perspective ◽  
Online Survey ◽  
Low Dose ◽  
Low Doses ◽  
Research Support ◽  
Serious Adverse Events ◽  
Patient Organizations

Background:The Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis Study (GLORIA) is an international investigator-initiated pragmatic randomized trial designed to study the effects of low-dose glucocorticoids (GCs) in elderly patients with Rheumatoid Arthritis (RA).The research team is also committed to promote a better understanding of the risks and benefits of these drugs among health professionals and patients. In order to achieve these goals, it is important to assess the current ideas and concerns of patients regarding GCs.Objectives:To evaluate the current patient perspective on the efficacy and risks of GCs in RA patients who are or have been treated with GCs.Methods:Patients with RA completed an online survey (with 5 closed questions regarding efficacy and safety) presented in their native language. RA patients were recruited through a variety of patient organizations representing three continents. Patients were invited to participate through national patient organizations. In the USA, patients were also invited to participate through MediGuard.org. Participants were asked for their level of agreement on a 5-point Likert scale.Results:1344 RA patients with exposure to GCs, from Brazil, USA, UK, Portugal, Netherlands, Germany and 24 other countries** participated: 89% female, mean age (SD) 52 (14) years and mean disease duration 13 (11) years. The majority of participants (84%) had ≥10 years of education. The duration of GCs exposure was 1.6 (4.2) years. The majority of participants had read articles or pamphlets on the benefits or harms of GC therapy.Regarding GCs efficacy (table 1), high levels of endorsement were found: about 2/3 of patients considered that GCs as very useful in their case, more than half considered that GCs were effective even at low doses, and agreed that GC improved RA symptoms within days.Regarding safety (table 1), 1/3 of the participants reported having suffered some form of serious adverse events (AEs) due to GCs, and 9% perceived this as “life-threatening. Adverse events had a serious impact on quality of life, according to about 1/3 of the respondents.Conclusion:Patients with RA exposed to GC report a strong conviction that GCs are very useful and effective for the treatment of their RA, even at low doses. This is accompanied by an important prevalence of serious AEs. Understanding the patient perspective can improve shared decision-making between patient and rheumatologist.Funding statement:This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634886.Disclosure of Interests:Tânia Santiago: None declared, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Maarten de Wit Grant/research support from: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Consultant of: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Speakers bureau: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Pedro Carvalho: None declared, Maarten Boers: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi., José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis

scholarly journals AB0249 SAFETY OF BARICITINIB IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS (RA): THE 2020 INTERIM REPORT FROM ALL-CASE POST MARKETING SURVEILLANCE IN CLINICAL PRACTICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1150.1-1150
Author(s):  
T. Fujii ◽  
T. Atsumi ◽  
N. Okamoto ◽  
N. Takahashi ◽  
N. Tamura ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Aspiration Pneumonia ◽  
Japanese Patients ◽  
Research Support ◽  
Serious Adverse Events ◽  
Chugai Pharmaceutical ◽  
Post Marketing Surveillance ◽  
Otsuka Pharmaceutical ◽  
Post Marketing

Background:An all-case post marketing surveillance (PMS) of baricitinib (Bari), that started in Sep 2017, collects safety and effectiveness for the first 24 wks of treatment and continues to collect serious adverse events (SAEs) for 3 yrs.Objectives:To evaluate Bari safety in RA patients (pt) in clinical practice.Methods:We report pt baseline demographics and adverse events (AEs) up to 24 wks for pts whose case report files for 24-wk data were completed as of Jun 2020.Results:Data from 3445 pts were analyzed (females=80%, mean age=64yr, mean RA duration 12yr). Bari dose regimen was as follows: 4mg, 60%, 2mg, 27%, 4mg→2mg, 5%, 2mg→4mg, 5%, and others, 2%. Concomitant use of MTX and glucocorticoid was 65% and 48%, respectively. 74% continued treatment for 24 wks. AE and SAE were recognized in 887 (26%) and 122 pts (4%), respectively. 6 pts died of pneumonia, aspiration pneumonia, bacterial pneumonia, cerebral infarction/ILD/aspiration pneumonia, adenocarcinoma, and colorectal cancer. Major AEs were as follows: herpes zoster=3%, liver dysfunction=3%, serious infection=1%, anemia=1%, hyperlipidemia=1%, malignancy=0.3%, interstitial pneumonia=0.2%, MACE=0.1%, and VTE=0.1%.Conclusion:Data do not show new safety concerns and encourage guideline-compliant use of Bari.Disclosure of Interests:Takao Fujii Speakers bureau: Chugai Pharmaceutical Co. Ltd.; Eisai Co. Ltd; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; Ono Pharmaceutical Co. Ltd., Consultant of: Asahikasei Pharma Corp, Grant/research support from: Asahikasei Pharma Corp; AbbVie Japan GK; Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Ono Pharmaceutical Co., Ltd., Tatsuya Atsumi Speakers bureau: AbbVie Japan GK; Astellas Pharma Inc.; Bristol-Myers Squibb Co. Ltd; Chugai Pharmaceutical Co. Ltd.; Daiichi Sankyo Co. Ltd.; Eisai Co. Ltd.; Eli Lilly Japan K.K.; Mitsubishi Tanabe Pharma Co.; Pfizer Japan Inc.; Takeda Pharmaceutical Co. Ltd., UCB Japan Co. Ltd., Consultant of: AbbVie Japan GK; AstraZeneca plc.; Boehringer Ingelheim Co. Ltd.; Medical & Biological Laboratories Co. Ltd.; Novartis Pharma K.K.; Ono Pharmaceutical Co. Ltd.; Pfizer Japan Inc., Grant/research support from: Astellas Pharma Inc., Alexion Inc.; Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co., Ltd.Pfizer Japan Inc.; Takeda Pharmaceutical Co. Ltd., Nami Okamoto Speakers bureau: AbbVie Japan GK; Asahikasei Pharma Co.; AYUMI Pharmaceutical Co.Eisai Co. Ltd; Bristol-Myers Squibb Co. Ltd.; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Pfizer Japan Inc.Sanofi K.K.; Chugai Pharmaceutical Co. Ltd.; Novartis Pharma Co.; Teijin Pharma Ltd.; Torii Pharmaceutical Co., Ltd., Nobunori Takahashi Speakers bureau: AbbVie Japan GK; Eisai Co. Ltd.; Mitsubishi Tanabe Pharma Co.; Pfizer Japan Inc.; Chugai Pharmaceutical Co., Ltd.; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; UCB Japan Co. Ltd.; Astellas Pharma Inc.; Bristol Myers Squibb Co. Ltd., Grant/research support from: Bristol Myers Squibb Co. Ltd., Naoto Tamura Speakers bureau: AbbVie Japan GK; Bristol Myers Squibb Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; Eisai Co. Ltd.; Eli Lilly Japan K.K.; Glaxo Smith Kline K.K.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co., Atsuo Nakajima: None declared, Ayako Nakajima Speakers bureau: AbbVie Japan GK; Actelion Pharmaceuticals Japan Ltd., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd.,Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Glaxo Smith Kline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Teijin Pharma Ltd., Grant/research support from: Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Hiroaki Matsuno Speakers bureau: Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Consultant of: Mochida Pharmaceutical Co., Ltd., Grant/research support from: Astellas Pharma Inc., Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K, Naoto Tsujimoto Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Atsushi Nishikawa Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Taeko Ishii Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Masataka Kuwana Speakers bureau: AbbVie Japan GK, Astellas Pharma Inc., Asahi Kasei Pharma Co., Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Medical &Biological Laboratories Co., Ltd.; Mitsubishi Tanabe Pharma Co.; Mochida Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Pfizer Japan Inc., Consultant of: Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Corbus Pharmaceuticals Holdings, Inc.; Medical &Biological Laboratories Co., Ltd.; Mochida Pharmaceutical Co., Ltd., Grant/research support from: Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Medical &Biological Laboratories Co., Ltd; Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., Ltd., Michiaki Takagi Speakers bureau: Yes, but sponsored lectures without COI in the academic meetings, only.

scholarly journals The Clinical Effect of Oral Vitamin D2 Supplementation on Psoriasis: A Double-Blind, Randomized, Placebo-Controlled Study

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Wareeporn Disphanurat ◽  
Wongsiya Viarasilpa ◽  
Panlop Chakkavittumrong ◽  
Padcha Pongcharoen
Keyword(s):  
Vitamin D ◽  
Placebo Group ◽  
Adverse Events ◽  
Clinical Effect ◽  
Vitamin D Supplementation ◽  
P Value ◽  
Vitamin D2 ◽  
Oral Vitamin ◽  
Pasi Score ◽  
The Mean

Background. There are limited randomized controlled trials of oral vitamin D supplementation in psoriasis, especially in Asia, and the results are inconclusive. Objective. To investigate the clinical effect of oral vitamin D supplementation on psoriasis. Methods. Patients with psoriasis were randomized to receive vitamin D2 60,000 IU or similar-looking placebo pills once every 2 weeks for 6 months. The primary outcome was improvement of the Psoriasis Area and Severity Index (PASI) score at 3 and 6 months after treatment. Serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone, and C-reactive protein and adverse events were monitored. The chi-square test, Fisher’s exact test, Student’s t-test, and Spearman’s correlation analysis were used in statistical analysis. Results. Of 50 subjects screened, 45 were eligible and randomized to the oral vitamin D2 group (n=23) or placebo group (n=22). At enrollment, the mean PASI score was 4.45, and 26.7% of patients had vitamin D deficiency. At 3 months, the oral vitamin D2 group had significantly higher PASI improvement than the placebo group (mean PASI improvement: 1.43 versus [vs.] -0.33, p-value=0.034; mean %PASI improvement: 34.21% vs. -1.85%, p-value=0.039). The mean serum 25(OH)D level was significantly higher in the oral vitamin D group than in the placebo group (27.4 vs. 22.4 ng/mL, p-value=0.029). Serum 25(OH)D concentrations were significantly inversely correlated with PASI scores at the 6-month follow-up. No major adverse event was observed overall. Conclusion. Oral vitamin D2 supplementation in patients with psoriasis increased the serum vitamin D level and significantly improved the treatment outcome without increasing adverse events. Trial Registration. This trial is registered with Thai Clinical Trials Registry TCTR20180613001.

A Controlled Trial of Extended-Release Guanfacine and Psychostimulants on Executive Function and ADHD

2018 ◽  
Vol 24 (2) ◽  
pp. 318-325 ◽  
Author(s):  
Judy P. M. van Stralen
Keyword(s):  
Executive Function ◽  
Adverse Events ◽  
Extended Release ◽  
Rating Scale ◽  
Controlled Trial ◽  
Severity Of Illness ◽  
P Value ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Stimulant Therapy

Objective: To evaluate the effectiveness of guanfacine extended-release (GXR) versus placebo as adjunct therapy to usual care stimulant therapy in improving executive function in children aged 6 to 12 years diagnosed with ADHD. Method: In this single center, double-blind placebo-controlled crossover trial, subjects continued to take their psychostimulant and were randomly assigned at baseline to receive active treatment or placebo first. Efficacy measures included Behavioural Rating Inventory of Executive Function (BRIEF-P), ADHD Rating Scale IV (ADHD-RS IV), and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events and vital signs. Results: Significant benefits of GXR plus psychostimulant were observed on BRIEF-P ( p value = .0392), ADHD-RS-IV ( p < .0001), CGI-S ( p = .0007), and CGI-I ( p = .003). There were no serious adverse events and no new safety signals. Conclusion: Use of GXR as adjunctive therapy to stimulant therapy significantly improves executive function in children with ADHD.

Efficacy and Safety of PEGPH20 in Pancreatic Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 17 ◽  
Author(s):  
Vinod Solipuram ◽  
Harish Gopalakrishna ◽  
Gayatri Naira ◽  
Akhila Mohan
Keyword(s):  
Pancreatic Cancer ◽  
Placebo Group ◽  
Febrile Neutropenia ◽  
Adverse Events ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Thromboembolic Events ◽  
Serious Adverse Events ◽  
Significant Difference

Introduction: Pancreatic cancer is an aggressive tumor that had an estimated 57,600 new cases and 47,050 deaths in 2020 in the US alone. Recent studies have targeted tumor microenvironment (TME) for better delivery of systemic chemotherapy like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles was identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR=0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), however, there was statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there is an increased incidence of serious adverse events with the use of PEGPH20 compared to standard therapies.

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