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

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

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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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.834 ◽

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

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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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2854 ◽

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

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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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2907 ◽

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)

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OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3213 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 54.1-54

Author(s):

S. Benamar ◽

C. Lukas ◽

C. Daien ◽

C. Gaujoux-Viala ◽

L. Gossec ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Treatment Response ◽

Univariate Analysis ◽

Group Versus ◽

Biological Database ◽

Lower Probability ◽

Research Support ◽

Early Ra ◽

Increased Risk

Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer

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Metastasiertes Melanom: Immuntherapie für Patienten ohne Krankheitsnachweis

Karger Kompass Onkologie ◽

10.1159/000518709 ◽

2021 ◽

pp. 1-2

Author(s):

Max Schlaak

Keyword(s):

Placebo Group ◽

Adverse Events ◽

Group Versus ◽

Stage Iv ◽

Recurrence Free Survival ◽

Free Survival ◽

Matching Placebo ◽

Grade 3 ◽

Stage Iv Melanoma ◽

Group 1

Background: Nivolumab and ipilimumab, alone or in combination, are widely used immunotherapeutic treatment options for patients with advanced – i.e., unresectable or metastatic – melanoma. This criterion, however, excludes patients with stage IV melanoma with no evidence of disease. We therefore aimed to evaluate the safety and efficacy of adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus a placebo in this patient population. Methods: We did a randomised, double-blind, placebo-controlled, phase 2 trial in 20 German academic medical centres. Eligible patients were aged 18–80 years with stage IV melanoma with no evidence of disease after surgery or radiotherapy. Key exclusion criteria included uveal or mucosal melanoma, previous therapy with checkpoint inhibitors, and any previous immunosuppressive therapy within the 30 days before study drug administration. Eligible patients were randomly assigned (1:1:1), using a central, interactive, online system, to the nivolumab plus ipilimumab group (1 mg/kg of intravenous nivolumab every 3 weeks plus 3 mg/kg of intravenous ipilimumab every 3 weeks for four doses, followed by 3 mg/kg of nivolumab every 2 weeks), nivolumab monotherapy group (3 mg/kg of intravenous nivolumab every 2 weeks plus ipilimumab-matching placebo during weeks 1–12), or double-matching placebo group. The primary endpoint was the recurrence-free survival in the intention-to-treat population. The results presented in this report reflect the prespecified interim analysis of recurrence-free survival after 90 events had been reported. This study is registered with ClinicalTrials.gov, NCT02523313, and is ongoing. Findings: Between Sept 2, 2015, and Nov 20, 2018, 167 patients were randomly assigned to receive nivolumab plus ipilimumab (n = 56), nivolumab (n = 59), or placebo (n = 52). As of July 2, 2019, at a median follow-up of 28.4 months (IQR 17.7–36.8), median recurrence-free survival was not reached in the nivolumab plus ipilimumab group, whereas median recurrence-free survival was 12.4 months (95% CI 5.3–33.3) in the nivolumab group and 6.4 months (3.3–9.6) in the placebo group. The hazard ratio for recurrence for the nivolumab plus ipilimumab group versus placebo group was 0.23 (97.5% CI 0.12–0.45; p < 0.0001), and for the nivolumab group versus placebo group was 0.56 (0.33–0.94; p = 0.011). In the nivolumab plus ipilimumab group, recurrence-free survival at 1 year was 75% (95% CI 61.0–84.9) and at 2 years was 70% (55.1–81.0); in the nivolumab group, 1-year recurrence-free survival was 52% (38.1–63.9) and at 2 years was 42% (28.6–54.5); and in the placebo group, this rate was 32% (19.8–45.3) at 1 year and 14% (5.9–25.7) at 2 years. Treatment-related grade 3–4 adverse events were reported in 71% (95% CI 57–82) of patients in the nivolumab plus ipilimumab group and in 27% (16–40) of those in the nivolumab group. Treatment-related adverse events of any grade led to treatment discontinuation in 34 (62%) of 55 patients in the nivolumab plus ipilimumab group and seven (13%) of 56 in the nivolumab group. Three deaths from adverse events were reported but were considered unrelated to the study treatment. Interpretation: Adjuvant therapy with nivolumab alone or in combination with ipilimumab increased recurrence-free survival significantly compared with placebo in patients with stage IV melanoma with no evidence of disease. The rates of grade 3–4 treatment-related adverse events in both active treatment groups were higher than the rates reported in previous pivotal trials done in advanced melanoma with measurable disease. Funding: Bristol-Myers Squibb.

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SAT0157 NINTEDANIB DOSE ADJUSTMENTS AND ADVERSE EVENTS IN PATIENTS WITH PROGRESSIVE AUTOIMMUNE DISEASE-RELATED INTERSTITIAL LUNG DISEASES IN THE INBUILD TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2322 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1019.1-1019

Author(s):

E. Volkmann ◽

I. Castellví ◽

S. Johnson ◽

E. Matteson ◽

J. Distler ◽

...

Keyword(s):

Placebo Group ◽

Autoimmune Disease ◽

Adverse Events ◽

Dose Reduction ◽

Treatment Interruption ◽

Treatment Discontinuation ◽

Research Support ◽

Treatment Interruptions ◽

Trial Drug ◽

Dose Reductions

Background:In the INBUILD trial in patients with progressive fibrosing ILDs, the adverse event (AE) profile of nintedanib was characterised predominantly by gastrointestinal AEs. Dose adjustments were used to manage AEs.Objectives:Assess AEs and dose adjustments in patients with autoimmune disease-related ILDs in the INBUILD trial.Methods:Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis were randomised to nintedanib 150 mg bid or placebo. Dose reductions to 100 mg bid and treatment interruptions were permitted to manage AEs. AEs over 52 weeks of treatment (or 28 days after last trial drug intake for patients who discontinued drug before week 52) were assessed in patients who received ≥1 dose of trial drug.Results:Of 663 patients in the INBUILD trial, 170 (82 nintedanib, 88 placebo) had autoimmune disease-related ILDs (89 RA-ILD, 39 SSc-ILD, 19 MCTD-ILD, 23 other autoimmune ILDs). In the nintedanib and placebo groups of patients with autoimmune disease-related ILDs, respectively, over 52 weeks, the proportions of patients with ≥1 dose reduction were 28.0% and 3.4%, with ≥1 treatment interruption were 31.7% and 10.2%, and with ≥1 dose reduction and/or treatment interruption were 40.2% and 12.5% (Table). Dose intensity (amount of drug administered divided by amount that would have been received had 150 mg bid been administered over 52 weeks or until permanent treatment discontinuation) was >90% in 80.5% of patients in the nintedanib group and 95.5% in the placebo group. AEs led to permanent treatment discontinuation in 17.1% and 10.2% of patients treated with nintedanib and placebo, respectively. Diarrhoea was the most common AE, reported in 63.4% and 27.3% of patients in the nintedanib and placebo groups, respectively. Diarrhoea AEs led to dose reduction, treatment interruption and permanent treatment discontinuation in 7.3%, 9.8% and 4.9% of patients in the nintedanib group, compared with 0%, 1.1% and 1.1% of patients in the placebo group, respectively. Of the nintedanib-treated patients who experienced ≥1 diarrhoea AE, 80.8% experienced 1 or 2 events and 76.9% experienced events that were mild at worst (Common Terminology Criteria for Adverse Events [CTCAE] grade 1).Conclusion:In the INBUILD trial, management of AEs via dose adjustments enabled most patients with autoimmune disease-related ILDs to remain on treatment for 52 weeks. Diarrhoea was the AE that most commonly led to dose adjustment.TableNintedanib(n=82)Placebo (n=88)Patients with ≥1 dose reduction or treatment interruption33 (40.2)11 (12.5)Patients with ≥1 dose reduction23 (28.0)3 (3.4)Total number of dose reductions253Patients with ≥1 dose re-escalation after dose reduction5 (6.1)2 (2.3)Patients with ≥1 treatment interruption26 (31.7)9 (10.2)Total number of treatment interruptions3211Total duration of treatment interruptions, days, mean (SD)20.1 (15.1)19.3 (20.7)Data are n (%) of patients unless otherwise indicated.Disclosure of Interests:Elizabeth Volkmann Grant/research support from: Forbius, Corbus Pharmaceuticals, Consultant of: Boehringer Ingelheim, Forbius, Speakers bureau: Boehringer Ingelheim, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Sindhu Johnson Grant/research support from: Boehringer Ingelheim, Corbus Pharmaceuticals, GlaxoSmithKline, Roche, Merck, Bayer, Consultant of: Boehringer Ingelheim, Ikaria, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, James Seibold Shareholder of: BriaCell, Pacific Therapeutics, Consultant of: Atlantic, Blade Therapeutics, Eicos Sciences, Eiger Biopharmaceuticals, Indalo Therapeutics, Mitsubishi Tanabe Pharma, Bayer, Xenikos, Boehringer Ingelheim, Camurus, Corbus Pharmaceuticals, EMD Serono, Speakers bureau: Boehringer Ingelheim, Ulrich Costabel Consultant of: Boehringer Ingelheim, Roche, Fibrogen, Global Blood Therapeutics, Speakers bureau: Boehringer Ingelheim, Roche, AstraZeneca, Alexandra James Employee of: Employee of Boehringer Ingelheim, Carl Coeck Employee of: Employee of Boehringer Ingelheim, Manuel Quaresma Employee of: Employee of Boehringer Ingelheim, Vincent Cottin Grant/research support from: Boehringer Ingelheim, Roche, Consultant of: Boehringer Ingelheim, Roche, Actelion, Bayer, Gilead Sciences, Novartis, Promedior, Celgene, Galapagos, Galecto. He was a member of the INBUILD trial Steering Committee., Speakers bureau: Actelion, Boehringer Ingelheim, Novartis, Roche, Sanofi

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Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation: A Meta-Analysis

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.281.any ◽

2019 ◽

Vol 28 (1) ◽

pp. 41-46 ◽

Cited By ~ 2

Author(s):

Mohammad Esmadi ◽

Dina Ahmad ◽

Alexander Hewlett

Keyword(s):

Placebo Group ◽

Adverse Events ◽

English Language ◽

Meta Analysis ◽

Group Versus ◽

Opioid Therapy ◽

Period Change ◽

Common Side Effect ◽

Spontaneous Bowel Movement ◽

Significant Difference

Background & Aim: Opioid induced constipation (OIC) is the most common side effect of opioid therapy. It can lead to a decreased quality of life. Naldemedine is a peripherally acting μ-opioid receptor antagonist that has been recently studied in randomized controlled trials (RCTs) for the management of OIC. The aim of this study is to perform a meta-analysis of existing clinical trials to estimate the efficacy and safety of naldemedine in opioid-induced constipation.Methods: A systematic search of PubMed, CINAHL, Scopus, Cochrane database of systematic reviews, and ClinicalTrials.gov registry was performed in March 2018. Two independent reviewers systematically identified prospective RCTs published in the English language that compared the effect of oral naldemedine versus placebo in adults with OIC. Meta-analysis was performed using a random effects model to assess the primary outcome: spontaneous bowel movement (SBM) responder rates. Assessed secondary outcomes were: a change in SBM frequency per week from baseline during the treatment period, change from baseline in the frequency of complete SBM and incidence of treatment-emergent adverse events. Review Manager 5.3 software program was utilized for statistical analysis.Results: Six RCTs met the inclusion criteria. A total of 2,762 patients were included in the meta-analysis. The proportion of SBM responders was significantly higher in the naldemedine group compared to the placebo group (56.4%, vs. 34.7%, p<0.00001). There was no statistically significant difference in treatment-emergent adverse events between naldemedine group and placebo group (mean odds ratio=1.18, p = 0.25, 95% CI: 0.89-1.55). Change in SBM frequency was higher in the naldemedine group versus placebo group (p<0.00001), as well as the change in complete SBM frequency.Conclusions: Naldemedine 0.2 mg daily significantly improved symptoms in patients with opioid-induced constipation and was generally well tolerated. These results support the use of naldemedine for the treatment of opioid-induced constipation.

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Urothelkarzinom: Was bringt der Einsatz von Angiogenesehemmern im metastasierten Stadium?

Karger Kompass Onkologie ◽

10.1159/000514701 ◽

2021 ◽

pp. 1-3

Author(s):

Julia Heinzelbecker

Keyword(s):

Overall Survival ◽

Placebo Group ◽

Adverse Events ◽

Urothelial Carcinoma ◽

Group Versus ◽

Progression Free Survival ◽

Free Survival ◽

Intention To Treat ◽

Platinum Refractory ◽

Advanced Urothelial Carcinoma

Background: Ramucirumab - an IgG1 vascular endothelial growth factor receptor 2 antagonist - plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomization was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3,5-13,9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4,1 months [95% CI 3,3-4,8] vs 2,8 months [2,6-2,9]; HR 0,696 [95% CI 0,573-0,845]; p=0,0002). Median overall survival was 9,4 months (95% CI 7,9-11,4) in the ramucirumab group versus 7,9 months (7,0-9,3) in the placebo group (stratified HR 0,887 [95% CI 0,724-1,086]; p=0,25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Funding: Eli Lilly and Company.

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Treatment of influenza and other acute respiratory viral infections in children: multicenter double-blind placebo-controlled randomized comparative clinical trial

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2021-66-1-131-139 ◽

2021 ◽

Vol 66 (1) ◽

pp. 131-139

Author(s):

L. V. Lukashova ◽

O. I. Afanasyeva ◽

E. V. Portnyagina ◽

A. N. Khmeleva ◽

N. P. Chernyshova

Keyword(s):

Clinical Trial ◽

Placebo Group ◽

Body Temperature ◽

Adverse Events ◽

Viral Infections ◽

Group Versus ◽

Adoptive Parents ◽

Efficacy And Safety ◽

Number Of Patients ◽

Respiratory Viral Infections

The article presents the main results of a randomized clinical trial of the efficacy and safety of Panavir®, rectal suppositories 100 μg, in children with influenza and other acute respiratory viral infections (ARVI).Characteristics of children and research methods. The trial included 40 children from 12 to 17 years old, the children were randomized into 2 groups: 20 children were treated with Panavir®, 1 rectal suppository per day for 7days, 20 children received placebo according to Panavir® regimen on the background of standard symptomatic therapy. The scientists monitored the efficacy criteria: the primary criteria: recovery time and the number of patients with successful treatment (normalization of axillary body temperature no later than 48 hours of therapy); the main secondary criteria: the timing of the normalization of body temperature, the disappearance of intoxication and catarrhal symptoms and satisfaction with the results of treatment by the parents /adoptive parents of patients on the IMPSS scale.Results. In the Group of Panavir®, the authors registered shorter mean recovery periods (4.5 days versus 7.4 days in the Group of Placebo), normalization of body temperature (39.1 hours versus 76.1 hours) and regression of intoxication manifestations (2.9 days versus 4.3 days) and catarrhal (3.4 days versus 5.6 days) syndromes (with statistical significance of intergroup differences). The treatment success was achieved in 85% of cases in the Panavir® Group versus 30% of cases in the Placebo Group; according to this criterion Panavir® exceeded placebo by at least 24.7%. At the end of the therapy course, 80% of the parents /adoptive parents were satisfied with the treatment results in the Panavir® Group versus 25% of cases in the Placebo Group. The authors determined a comparable incidence of adverse events in the Panavir® and Placebo Groups. There were no adverse events associated with the administration of Panavir®.Conclusion. This study established the efficacy and safety of Panavir® in the treatment of children of 12-17 years old with influenza and other acute respiratory viral infections. This drug with a combined antiviral and immunomodulatory effect is promising for pediatric practice.

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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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3711 ◽

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

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