Mathias Rolke - Academia.edu (original) (raw)

Papers by Mathias Rolke

Research paper thumbnail of Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study

The Lancet Respiratory Medicine, 2022

BACKGROUND Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal ... more BACKGROUND Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. SOURCE evaluated the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma. METHODS We conducted this phase 3, multicentre, randomised, double-blind, placebo-controlled study across 60 sites in seven countries. Participants aged 18-80 years with physician-diagnosed asthma, who had been receiving medium-dose or high-dose inhaled corticosteroids and had at least one asthma exacerbation in the 12 months before screening were eligible. Patients who were receiving medium-dose inhaled corticosteroids must have had their dose increased to a high dose for at least 3 months before screening. After an oral corticosteroid optimisation phase of up to 8 weeks, participants were randomly assigned according to a computer-generated fixed block randomisation sequence to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks during a 48 week treatment period (4 week induction phase, 36 week oral corticosteroid reduction phase, and 8 week maintenance phase). Randomisation was stratified by region. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoint was the categorised percentage reduction from baseline in daily oral corticosteroid dose at week 48 without the loss of asthma control. Efficacy and safety endpoints were assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03406078. FINDINGS Between March 5, 2018, and Sept 27, 2019, 150 participants were randomly assigned to receive tezepelumab 210 mg (n=74) or placebo (n=76). The cumulative odds of achieving a category of greater percentage reduction in an oral corticosteroid dose for daily maintenance at week 48 were similar with tezepelumab or placebo in the overall population (odds ratio [OR] 1·28 [95% CI 0·69-2·35], p=0·43; the primary endpoint was not met). The cumulative odds were higher with tezepelumab than with placebo in participants with baseline blood eosinophil counts of at least 150 cells per μL (2·58 [1·16-5·75]), but not in participants with counts below 150 cells per μL (0·40 [0·14-1·13]). Tezepelumab was well tolerated, with no safety concerns identified. 53 (72%) of 74 tezepelumab-assigned participants and 65 (86%) of 76 placebo-assigned participants reported an adverse event. Serious adverse events were reported in 12 (16%) participants in the tezepelumab group and 16 (21%) participants in the placebo group. INTERPRETATION We did not observe a significant improvement in oral corticosteroid dose reduction with tezepelumab versus placebo in the overall population of this oral corticosteroid-sparing study, although an improvement was observed in participants with baseline blood eosinophil counts of at least 150 cells per μL. FUNDING AstraZeneca and Amgen.

Research paper thumbnail of Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

The Lancet Respiratory Medicine, 2018

Background Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody tha... more Background Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma. Methods We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were rerandomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12-17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542).

Research paper thumbnail of β 2 -Sympathomimetika: Gefahren in der Asthmatherapie? Lehren aus der SMART1-Studie - Erwiderung

DMW - Deutsche Medizinische Wochenschrift, 2007

Research paper thumbnail of Empfehlungen der Deutschen Atemwegsliga zur Spirometrie

Research paper thumbnail of Guidelines for Diagnosis and Treatment of Asthma Patients

Pneumologie, 2006

Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimm... more Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimmung des Verlages. Tablette (2 mg) Kinder 3 ± 6 Jahre: 3 ± 4 1 / 2 ± 1 Tbl. Kinder 7 ± 14 Jahre: 3 ± 4 1 Tbl. Kinder über 14 Jahre und Erwachsene: 3 ± 4 1 ± 2 Tbl. Tablette (4 mg) Erwachsene: 3 ± 4 1 / 2 ± 1 Tbl. Retard−Tablette (4 mg) Kinder 3 ± 12 Jahre: 2 1 Tbl. Retard−Tablette (8 mg) Kinder über 12 Jahre und Erwachsene: 2 1 Tbl. MTD: 2 Tbl. Tablette (2,5 mg) Kinder 3 ± 6 Jahre: 2 1 / 2 Tbl. Kinder 7 ± 14 Jahre: 2 1 Tbl. Kinder über 14 Jahre und Erwachsene: 2 ± 3 1 ± 2 Tbl. Retard−Tablette (7,5 mg) Erwachsene: 2 1 Tbl. MTD: 2 Tbl. siehe kurz− und langwirksame â 2 −Sympathomimetika Fortsetzung auf der nächsten Seite

Research paper thumbnail of Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma 2005

Medizinische Klinik, 2006

Bei Asthma muss eine allergologische Stufendiagnostik erfolgen, bestehend aus Anamnese (einschlie... more Bei Asthma muss eine allergologische Stufendiagnostik erfolgen, bestehend aus Anamnese (einschließlich häuslicher und beruflicher Allergene) und Hauttests mit den häufigsten Aeroallergenen, bei anamnestischem Verdacht auch Nahrungsmittelallergenen, ersatzweise Bestimmung des spezifischen IgE im Serum. Weiterführende Abklärung durch nasale, konjunktivale oder bronchiale Provokationstests nur bei Konsequenzen (spezifische Immuntherapie, Berufsallergie). Wichtig: Der Nachweis einer Sensibilisierung darf nicht automatisch mit der Diagnose Asthma bzw. dem Nachweis von dessen Ursachen gleichgesetzt werden. Therapie Das Ziel der Asthmatherapie ist definiert als bestmögliche Asthmakontrolle durch Reduktion der asthmatischen Entzündung. Geeignete Kontrollparameter sind: Symptomfreiheit (Anfälle, Atemnot, Husten, nächtliches Erwachen); Fehlen von Exazerbationen, Notfallbehandlungen, Bedarf an zusätzlichen rasch wirksamen β 2-Sympathomimetika zur Symptomlinderung, Einschränkung der psychischen und physischen Leistungsfähigkeit. Die Lungenfunktion sollte normal sein und die zirkadiane PEF-Variabilität < 20% betragen. Verlaufskontrollen sind individuell nach Schweregrad (z.B. alle 3 Monate) festzulegen. Die Komponenten des Asthmamanagements bestehen aus: Präven-tion, medikamentöser Therapie, nichtmedikamentösen Therapiemaßnahmen inkl. spezifischer Immuntherapie, Patientenschulung, Raucherentwöhnung, körperlichem Training (Asthma-Sport), Normalisierung des Gewichts, psychosozialer Betreuung und Rehabilitation. In der Asthmatherapie spielt die Sekundärprävention eine Rolle: Meidung von Asthmaauslösern, aktivem

Research paper thumbnail of Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma

New England Journal of Medicine, 2014

Background Many patients with severe asthma require regular treatment with oral glucocorticoids d... more Background Many patients with severe asthma require regular treatment with oral glucocorticoids despite the use of high-dose inhaled therapy. However, the regular use of systemic glucocorticoids can result in serious and often irreversible adverse effects. Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5, has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma. Conclusions In patients requiring daily oral glucocorticoid therapy to maintain asthma control, mepolizumab had a significant glucocorticoid-sparing effect, reduced exacerbations, and improved control of asthma symptoms. (Funded by GlaxoSmithKline; SIRIUS ClinicalTrials.gov number, NCT01691508.

Research paper thumbnail of Body plethysmography--its principles and clinical use

Respiratory medicine, 2011

Body plethysmography allows to assess functional residual capacity (FRC(pleth)) and specific airw... more Body plethysmography allows to assess functional residual capacity (FRC(pleth)) and specific airway resistance (sRaw) as primary measures. In combination with deep expirations and inspirations, total lung capacity (TLC) and residual volume (RV) can be determined. Airway resistance (Raw) is calculated as the ratio of sRaw to FRC(pleth). Raw is a measure of airway obstruction and indicates the alveolar pressure needed to establish a flow rate of 1 L s(-1). In contrast, sRaw can be interpreted as the work to be performed by volume displacement to establish this flow rate. These measures represent different functional aspects and should both be considered. The measurement relies on the fact that generation of airflow needs generation of pressure. Pressure generation means that a mass of air is compressed or decompressed relative to its equilibrium volume. This difference is called "shift volume". As the body box is sealed and has rigid walls, its free volume experiences the sa...

Research paper thumbnail of Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study

The Lancet Respiratory Medicine, 2022

BACKGROUND Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal ... more BACKGROUND Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. SOURCE evaluated the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma. METHODS We conducted this phase 3, multicentre, randomised, double-blind, placebo-controlled study across 60 sites in seven countries. Participants aged 18-80 years with physician-diagnosed asthma, who had been receiving medium-dose or high-dose inhaled corticosteroids and had at least one asthma exacerbation in the 12 months before screening were eligible. Patients who were receiving medium-dose inhaled corticosteroids must have had their dose increased to a high dose for at least 3 months before screening. After an oral corticosteroid optimisation phase of up to 8 weeks, participants were randomly assigned according to a computer-generated fixed block randomisation sequence to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks during a 48 week treatment period (4 week induction phase, 36 week oral corticosteroid reduction phase, and 8 week maintenance phase). Randomisation was stratified by region. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoint was the categorised percentage reduction from baseline in daily oral corticosteroid dose at week 48 without the loss of asthma control. Efficacy and safety endpoints were assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03406078. FINDINGS Between March 5, 2018, and Sept 27, 2019, 150 participants were randomly assigned to receive tezepelumab 210 mg (n=74) or placebo (n=76). The cumulative odds of achieving a category of greater percentage reduction in an oral corticosteroid dose for daily maintenance at week 48 were similar with tezepelumab or placebo in the overall population (odds ratio [OR] 1·28 [95% CI 0·69-2·35], p=0·43; the primary endpoint was not met). The cumulative odds were higher with tezepelumab than with placebo in participants with baseline blood eosinophil counts of at least 150 cells per μL (2·58 [1·16-5·75]), but not in participants with counts below 150 cells per μL (0·40 [0·14-1·13]). Tezepelumab was well tolerated, with no safety concerns identified. 53 (72%) of 74 tezepelumab-assigned participants and 65 (86%) of 76 placebo-assigned participants reported an adverse event. Serious adverse events were reported in 12 (16%) participants in the tezepelumab group and 16 (21%) participants in the placebo group. INTERPRETATION We did not observe a significant improvement in oral corticosteroid dose reduction with tezepelumab versus placebo in the overall population of this oral corticosteroid-sparing study, although an improvement was observed in participants with baseline blood eosinophil counts of at least 150 cells per μL. FUNDING AstraZeneca and Amgen.

Research paper thumbnail of Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

The Lancet Respiratory Medicine, 2018

Background Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody tha... more Background Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma. Methods We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were rerandomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12-17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542).

Research paper thumbnail of β 2 -Sympathomimetika: Gefahren in der Asthmatherapie? Lehren aus der SMART1-Studie - Erwiderung

DMW - Deutsche Medizinische Wochenschrift, 2007

Research paper thumbnail of Empfehlungen der Deutschen Atemwegsliga zur Spirometrie

Research paper thumbnail of Guidelines for Diagnosis and Treatment of Asthma Patients

Pneumologie, 2006

Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimm... more Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimmung des Verlages. Tablette (2 mg) Kinder 3 ± 6 Jahre: 3 ± 4 1 / 2 ± 1 Tbl. Kinder 7 ± 14 Jahre: 3 ± 4 1 Tbl. Kinder über 14 Jahre und Erwachsene: 3 ± 4 1 ± 2 Tbl. Tablette (4 mg) Erwachsene: 3 ± 4 1 / 2 ± 1 Tbl. Retard−Tablette (4 mg) Kinder 3 ± 12 Jahre: 2 1 Tbl. Retard−Tablette (8 mg) Kinder über 12 Jahre und Erwachsene: 2 1 Tbl. MTD: 2 Tbl. Tablette (2,5 mg) Kinder 3 ± 6 Jahre: 2 1 / 2 Tbl. Kinder 7 ± 14 Jahre: 2 1 Tbl. Kinder über 14 Jahre und Erwachsene: 2 ± 3 1 ± 2 Tbl. Retard−Tablette (7,5 mg) Erwachsene: 2 1 Tbl. MTD: 2 Tbl. siehe kurz− und langwirksame â 2 −Sympathomimetika Fortsetzung auf der nächsten Seite

Research paper thumbnail of Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma 2005

Medizinische Klinik, 2006

Bei Asthma muss eine allergologische Stufendiagnostik erfolgen, bestehend aus Anamnese (einschlie... more Bei Asthma muss eine allergologische Stufendiagnostik erfolgen, bestehend aus Anamnese (einschließlich häuslicher und beruflicher Allergene) und Hauttests mit den häufigsten Aeroallergenen, bei anamnestischem Verdacht auch Nahrungsmittelallergenen, ersatzweise Bestimmung des spezifischen IgE im Serum. Weiterführende Abklärung durch nasale, konjunktivale oder bronchiale Provokationstests nur bei Konsequenzen (spezifische Immuntherapie, Berufsallergie). Wichtig: Der Nachweis einer Sensibilisierung darf nicht automatisch mit der Diagnose Asthma bzw. dem Nachweis von dessen Ursachen gleichgesetzt werden. Therapie Das Ziel der Asthmatherapie ist definiert als bestmögliche Asthmakontrolle durch Reduktion der asthmatischen Entzündung. Geeignete Kontrollparameter sind: Symptomfreiheit (Anfälle, Atemnot, Husten, nächtliches Erwachen); Fehlen von Exazerbationen, Notfallbehandlungen, Bedarf an zusätzlichen rasch wirksamen β 2-Sympathomimetika zur Symptomlinderung, Einschränkung der psychischen und physischen Leistungsfähigkeit. Die Lungenfunktion sollte normal sein und die zirkadiane PEF-Variabilität < 20% betragen. Verlaufskontrollen sind individuell nach Schweregrad (z.B. alle 3 Monate) festzulegen. Die Komponenten des Asthmamanagements bestehen aus: Präven-tion, medikamentöser Therapie, nichtmedikamentösen Therapiemaßnahmen inkl. spezifischer Immuntherapie, Patientenschulung, Raucherentwöhnung, körperlichem Training (Asthma-Sport), Normalisierung des Gewichts, psychosozialer Betreuung und Rehabilitation. In der Asthmatherapie spielt die Sekundärprävention eine Rolle: Meidung von Asthmaauslösern, aktivem

Research paper thumbnail of Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma

New England Journal of Medicine, 2014

Background Many patients with severe asthma require regular treatment with oral glucocorticoids d... more Background Many patients with severe asthma require regular treatment with oral glucocorticoids despite the use of high-dose inhaled therapy. However, the regular use of systemic glucocorticoids can result in serious and often irreversible adverse effects. Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5, has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma. Conclusions In patients requiring daily oral glucocorticoid therapy to maintain asthma control, mepolizumab had a significant glucocorticoid-sparing effect, reduced exacerbations, and improved control of asthma symptoms. (Funded by GlaxoSmithKline; SIRIUS ClinicalTrials.gov number, NCT01691508.

Research paper thumbnail of Body plethysmography--its principles and clinical use

Respiratory medicine, 2011

Body plethysmography allows to assess functional residual capacity (FRC(pleth)) and specific airw... more Body plethysmography allows to assess functional residual capacity (FRC(pleth)) and specific airway resistance (sRaw) as primary measures. In combination with deep expirations and inspirations, total lung capacity (TLC) and residual volume (RV) can be determined. Airway resistance (Raw) is calculated as the ratio of sRaw to FRC(pleth). Raw is a measure of airway obstruction and indicates the alveolar pressure needed to establish a flow rate of 1 L s(-1). In contrast, sRaw can be interpreted as the work to be performed by volume displacement to establish this flow rate. These measures represent different functional aspects and should both be considered. The measurement relies on the fact that generation of airflow needs generation of pressure. Pressure generation means that a mass of air is compressed or decompressed relative to its equilibrium volume. This difference is called "shift volume". As the body box is sealed and has rigid walls, its free volume experiences the sa...