Background: Many patients with moderately to severely active Crohn’s disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn’s disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study. Methods: We did a phase 2, randomised, multicentre, double-blind trial. Adult patients with moderately to severely active Crohn’s disease were randomly allocated with a computer-generated randomisation schedule to receive one of five treatment groups, with regimens consisting of an intravenous induction phase transitioning to a subcutaneous maintenance phase starting at week 12 in a treat-through design: (1) guselkumab 200→100 mg group (200 mg intravenous at weeks 0, 4, and 8, then 100 mg subcutaneous every 8 weeks; (2) guselkumab 600→200 mg group (600 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (3) guselkumab 1200→200 mg group (1200 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (4) ustekinumab group (approximately 6 mg/kg intravenous at week 0, then 90 mg subcutaneous every 8 weeks); or (5) placebo group (placebo induction followed by either placebo maintenance [for those with CDAI clinical response at week 12] or crossover to ustekinumab [for those without CDAI clinical response at week 12]). Endpoints assessed at week 48 included CDAI remission (CDAI score <150), endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD score ≤2), and endoscopic remission (SES-CD score ≤2) in the primary efficacy analysis population of all randomised patients who received at least one dose of study drug, excluding those discontinued during a temporary study pause. Safety analyses included all randomised patients who received at least one study drug dose. This trial is registered at Clinical Trials.gov (NCT03466411) and is active but not recruiting. Findings: Among 700 patients screened, 309 (112 biologic-naive; 197 biologic-experienced) were included in the primary efficacy analysis population: 61 in the guselkumab 200→100 mg group, 63 in the guselkumab 600→200 mg group, 61 in the guselkumab 1200→200 mg group, 63 in the ustekinumab group, and 61 in the placebo group. 126 (41%) women and 183 (59%) men were included, with median age 36·0 years (IQR 28·0-49·0). At week 48, the numbers of patients with CDAI clinical remission were 39 (64%) in the guselkumab 200→100 mg group, 46 (73%) in the guselkumab 600→200 mg group, 35 (57%) in the guselkumab 1200→200 mg group, and 37 (59%) in the ustekinumab group. The corresponding numbers of patients with endoscopic response were 27 (44%), 29 (46%), 27 (44%), and 19 (30%), respectively, and endoscopic remission was seen in 11 (18%), 11 (17%), 20 (33%), and four (6%) patients, respe
{"title":"Morbus Crohn: Vielversprechende Behandlungsoption eines neuen IL-23-Inhibitors auf dem Weg zur Zulassung","authors":"E. Schnoy","doi":"10.1159/000538956","DOIUrl":"https://doi.org/10.1159/000538956","url":null,"abstract":"Background: Many patients with moderately to severely active Crohn’s disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn’s disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study. Methods: We did a phase 2, randomised, multicentre, double-blind trial. Adult patients with moderately to severely active Crohn’s disease were randomly allocated with a computer-generated randomisation schedule to receive one of five treatment groups, with regimens consisting of an intravenous induction phase transitioning to a subcutaneous maintenance phase starting at week 12 in a treat-through design: (1) guselkumab 200→100 mg group (200 mg intravenous at weeks 0, 4, and 8, then 100 mg subcutaneous every 8 weeks; (2) guselkumab 600→200 mg group (600 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (3) guselkumab 1200→200 mg group (1200 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (4) ustekinumab group (approximately 6 mg/kg intravenous at week 0, then 90 mg subcutaneous every 8 weeks); or (5) placebo group (placebo induction followed by either placebo maintenance [for those with CDAI clinical response at week 12] or crossover to ustekinumab [for those without CDAI clinical response at week 12]). Endpoints assessed at week 48 included CDAI remission (CDAI score <150), endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD score ≤2), and endoscopic remission (SES-CD score ≤2) in the primary efficacy analysis population of all randomised patients who received at least one dose of study drug, excluding those discontinued during a temporary study pause. Safety analyses included all randomised patients who received at least one study drug dose. This trial is registered at Clinical Trials.gov (NCT03466411) and is active but not recruiting. Findings: Among 700 patients screened, 309 (112 biologic-naive; 197 biologic-experienced) were included in the primary efficacy analysis population: 61 in the guselkumab 200→100 mg group, 63 in the guselkumab 600→200 mg group, 61 in the guselkumab 1200→200 mg group, 63 in the ustekinumab group, and 61 in the placebo group. 126 (41%) women and 183 (59%) men were included, with median age 36·0 years (IQR 28·0-49·0). At week 48, the numbers of patients with CDAI clinical remission were 39 (64%) in the guselkumab 200→100 mg group, 46 (73%) in the guselkumab 600→200 mg group, 35 (57%) in the guselkumab 1200→200 mg group, and 37 (59%) in the ustekinumab group. The corresponding numbers of patients with endoscopic response were 27 (44%), 29 (46%), 27 (44%), and 19 (30%), respectively, and endoscopic remission was seen in 11 (18%), 11 (17%), 20 (33%), and four (6%) patients, respe","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series. Methods: We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day. Results: Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9–34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004).
{"title":"Behandlung der eosinophilen Granulomatose mit Polyangiitis: Ist Benralizumab eine Alternative?","authors":"P. Xanthouli","doi":"10.1159/000538827","DOIUrl":"https://doi.org/10.1159/000538827","url":null,"abstract":"Background: Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series. Methods: We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day. Results: Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9–34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004).","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":" 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140686606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). According to expert statements, not all SSc-ILD patients require pharmacological therapy. Objectives: To describe disease characteristics and disease course in untreated SSc-ILD patients in two well characterised SSc-ILD cohorts. Methods: Patients were classified as treated if they had received a potential ILD-modifying drug. ILD progression in untreated patients was defined as (1) decline in forced vital capacity (FVC) from baseline of ≥10% or (2) decline in FVC of 5%–9% associated with a decline in diffusing capacity for carbon monoxide (DLCO)≥15% over 12 ± 3 months or (3) start of any ILD-modifying treatment or (4) increase in the ILD extent during follow-up. Multivariable logistic regression was performed to identify factors associated with non-prescription of ILD-modifying treatment at baseline. Prognostic factors for progression in untreated patients were tested by multivariate Cox regression. Results: Of 386 SSc-ILD included patients, 287 (74%) were untreated at baseline. Anticentromere antibodies (OR: 6.75 (2.16–21.14), p=0.001), limited extent of ILD (OR: 2.39 (1.19–4.82), p=0.015), longer disease duration (OR: 1.04 (1.00–1.08), p=0.038) and a higher DLCO (OR: 1.02 (1.01–1.04), p=0.005) were independently associated with no ILD-modifying treatment at baseline. Among 234 untreated patients, the 3 year cumulative incidence of progression was 39.9% (32.9–46.2). Diffuse cutaneous SSc and extensive lung fibrosis independently predicted ILD progression in untreated patients. Conclusion: As about 40% of untreated patients show ILD progression after 3 years and effective and safe therapies for SSc-ILD are available, our results support a change in clinical practice in selecting patients for treatment.
{"title":"Treat hard and early in SSc-ILD: milde ILD ist immer noch ILD","authors":"P. Xanthouli","doi":"10.1159/000538830","DOIUrl":"https://doi.org/10.1159/000538830","url":null,"abstract":"Background: Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). According to expert statements, not all SSc-ILD patients require pharmacological therapy. Objectives: To describe disease characteristics and disease course in untreated SSc-ILD patients in two well characterised SSc-ILD cohorts. Methods: Patients were classified as treated if they had received a potential ILD-modifying drug. ILD progression in untreated patients was defined as (1) decline in forced vital capacity (FVC) from baseline of ≥10% or (2) decline in FVC of 5%–9% associated with a decline in diffusing capacity for carbon monoxide (DLCO)≥15% over 12 ± 3 months or (3) start of any ILD-modifying treatment or (4) increase in the ILD extent during follow-up. Multivariable logistic regression was performed to identify factors associated with non-prescription of ILD-modifying treatment at baseline. Prognostic factors for progression in untreated patients were tested by multivariate Cox regression. Results: Of 386 SSc-ILD included patients, 287 (74%) were untreated at baseline. Anticentromere antibodies (OR: 6.75 (2.16–21.14), p=0.001), limited extent of ILD (OR: 2.39 (1.19–4.82), p=0.015), longer disease duration (OR: 1.04 (1.00–1.08), p=0.038) and a higher DLCO (OR: 1.02 (1.01–1.04), p=0.005) were independently associated with no ILD-modifying treatment at baseline. Among 234 untreated patients, the 3 year cumulative incidence of progression was 39.9% (32.9–46.2). Diffuse cutaneous SSc and extensive lung fibrosis independently predicted ILD progression in untreated patients. Conclusion: As about 40% of untreated patients show ILD progression after 3 years and effective and safe therapies for SSc-ILD are available, our results support a change in clinical practice in selecting patients for treatment.","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":"8 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn’s disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies. Methods: PROFILE (PRedicting Outcomes For Crohn’s disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn’s disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP > upper limit of normal or faecal calprotectin ≥200 μg/g, or both), while remission was the converse – ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 μg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228). Findings: Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33.6 years [SD 13.2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0–191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI –15 to 15; p = 0.944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p < 0.0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infection
背景：新诊断出的克罗恩病患者的治疗策略和临床结果差异很大。我们通过评估随机接受自上而下（即使用英夫利昔单抗和免疫调节剂的早期联合免疫抑制）或加速阶梯（常规）治疗策略的患者的疗效，评估了使用假定预后生物标志物指导治疗的效果。研究方法PROFILE（使用常规生物标志物预测克罗恩病治疗结果）是一项多中心、开放标签、生物标志物分层随机对照试验，招募了新诊断为活动性克罗恩病（哈维-布拉德肖指数≥7，C反应蛋白或粪钙蛋白升高或两者同时升高，以及内镜下活动性炎症证据）的成人患者。潜在参与者需抽血检测从 T 细胞转录特征中提取的预后生物标志物（PredictSURE-IBD 检测）。检测结束后，患者通过一个安全的在线平台随机分配到自上而下或加速阶梯式治疗，治疗按生物标志物亚组（IBDhi 或 IBDlo）、内镜炎症（轻度、中度或重度）和范围（结肠或其他）进行分层。在整个试验过程中，对生物标记物状态保持盲法。主要终点是第 48 周的持续无类固醇和无手术缓解。缓解的定义是所有就诊时症状和炎症标志物的综合情况。复发要求症状活跃（HBI ≥5）加炎症指标升高（CRP >正常值上限或粪便钙蛋白≥200 μg/g，或两者均有），而缓解则相反，即症状平息（HBI <5）或炎症指标缓解（CRP ≤正常值上限和钙蛋白<200 μg/g）或两者均有。分析是在全面分析（意向治疗）人群中进行的。该试验已完成并注册（ISRCTN11808228）。研究结果2017年12月29日至2022年1月5日期间，386名患者（平均年龄33.6岁[SD 13.2]；女性179人[46%]，男性207人[54%]）被随机分配到自上而下组193人和加速向上组193人。从确诊到参加试验的中位时间为 12 天（0-191 天不等）。379名参与者（自上而下组189人；加速阶梯组190人）的主要结果数据可用。生物标志物与治疗之间不存在交互效应（绝对差异为1个百分点，95% CI -15至15；P = 0.944）。自上而下组中无类固醇和无手术的持续缓解率明显高于加速阶梯治疗组（189例患者中的149例[79%] vs 190例患者中的29例[15%]，绝对差异为64个百分点，95% CI为57至72；P < 0.0001）。自上而下组的不良事件（包括疾病复发）和严重不良事件少于加速向上组（不良事件：168 例 vs 315 例；严重不良事件：15 例 vs 42 例），需要进行腹部手术的并发症少（1 例 vs 10 例），严重感染无差异（3 例 vs 8 例）。释义英夫利西单抗加免疫调节剂的自上而下联合治疗在1年后取得的疗效大大优于自下而上的加速治疗。生物标记物未显示出临床效用。对于新确诊的活动性克罗恩病患者，自上而下的治疗应被视为标准治疗方法。
{"title":"Morbus Crohn: Top-down-Behandlungsschema erreicht substanziell höhere Remissionsraten, jedoch unabhängig von einem vorgeschlagenen Biomarker","authors":"B. Bengsch","doi":"10.1159/000538712","DOIUrl":"https://doi.org/10.1159/000538712","url":null,"abstract":"Background: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn’s disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies. Methods: PROFILE (PRedicting Outcomes For Crohn’s disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn’s disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP > upper limit of normal or faecal calprotectin ≥200 μg/g, or both), while remission was the converse – ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 μg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228). Findings: Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33.6 years [SD 13.2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0–191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI –15 to 15; p = 0.944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p < 0.0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infection","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":"23 s1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140715244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Schuitema, Suzanne I. Anjie, Agnies M. van Eeghen, Sander W. Tas, Mark Löwenberg
Wir stellen eine Patientin mit Morbus Crohn vor, die während der Behandlung mit hochdosiertem Upadacitinib erhöhte Kreatinphosphokinase-Werte und eine Myopathie zeigte, und bieten dem Leser praktische Tipps zur Unterbrechung und erneuten Verarbeichung von Upadacitinib, wobei die Notwendigkeit einer angemessenen Überwachung zu betonen ist.
{"title":"Symptomatische Erhöhung der Kreatinphosphokinase bei einer Patientin mit Morbus Crohn, verursacht durch Upadacitinib","authors":"Anna Schuitema, Suzanne I. Anjie, Agnies M. van Eeghen, Sander W. Tas, Mark Löwenberg","doi":"10.1159/000538605","DOIUrl":"https://doi.org/10.1159/000538605","url":null,"abstract":"Wir stellen eine Patientin mit Morbus Crohn vor, die während der Behandlung mit hochdosiertem Upadacitinib erhöhte Kreatinphosphokinase-Werte und eine Myopathie zeigte, und bieten dem Leser praktische Tipps zur Unterbrechung und erneuten Verarbeichung von Upadacitinib, wobei die Notwendigkeit einer angemessenen Überwachung zu betonen ist.","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":"28 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140714562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Advances in rheumatoid arthritis (RA) treatment, highlighted by biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), have altered the paradigm of RA treatment in the last decade. Therefore, real-world clinical evidence is needed to understand how treatment strategies and outcomes have changed. Methods: Using an observational cohort of RA from 2012 to 2021, we collected cross-sectional data of RA patients annually to analyze a trend in RA management. For patients who initiated b/tsDMRDs, we evaluated treatment outcomes between b/tsDMARDs. Mixed-effect models were applied to examine the statistical implications of changes over time in treatment outcomes with a background adjustment. Results: We analyzed annual cross-sectional data from 5070 patients and longitudinal data from 1816 patients in whom b/tsDMARDs were initiated between 2012 and 2021. b/tsDMARD use increased, whereas glucocorticoid use decreased from 2012 to 2021. Disease activity and functional disability measures improved over time. The percentage of tsDMARD prescriptions considerably increased. All b/tsDMARDs showed clinical improvements in disease activity and functional disability. Statistically, TNFi showed better short-term improvements in b/tsDMARD-naïve patients, while IL6Ri demonstrated significant long-term benefits. IL6Ri had better retention rates in switched patients. After adjustment for patient characteristics, the annual change of RA disease activity and functional disability fared significantly better from 2012 to 2021. Conclusions: With the development of new RA therapeutics, overall treatment outcomes advanced in the past decade.
背景：过去十年中，类风湿关节炎（RA）治疗的进展，特别是生物疾病修饰抗风湿药（bDMARDs）和靶向合成DMARDs（tsDMARDs），改变了RA的治疗模式。因此，需要真实世界的临床证据来了解治疗策略和疗效发生了怎样的变化。方法：我们利用 2012 年至 2021 年的 RA 观察队列，每年收集 RA 患者的横断面数据，分析 RA 治疗的趋势。对于开始使用b/tsDMRDs的患者，我们评估了b/tsDMARDs之间的治疗效果。我们采用混合效应模型来研究治疗结果随时间变化的统计影响，并进行了背景调整。结果我们分析了 5070 名患者的年度横断面数据和 1816 名患者的纵向数据，这些患者在 2012 年至 2021 年期间开始使用 b/tsDMARDs。随着时间的推移，疾病活动度和功能性残疾指标有所改善。tsDMARD处方的比例大幅增加。所有b/tsDMARDs在疾病活动度和功能障碍方面均有临床改善。据统计，TNFi对b/tsDMARD无效患者的短期改善效果更好，而IL6Ri的长期疗效显著。IL6Ri在转换患者中的保留率更高。对患者特征进行调整后，从2012年到2021年，RA疾病活动度和功能障碍的年度变化明显更好。结论：随着新的RA治疗药物的开发，过去十年的总体治疗效果有所提高。
{"title":"Rheumatoide Arthritis: Langzeitverläufe haben sich seit Einführung von Biologika und gezielter Therapie verbessert","authors":"S. Adler","doi":"10.1159/000538592","DOIUrl":"https://doi.org/10.1159/000538592","url":null,"abstract":"Background: Advances in rheumatoid arthritis (RA) treatment, highlighted by biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), have altered the paradigm of RA treatment in the last decade. Therefore, real-world clinical evidence is needed to understand how treatment strategies and outcomes have changed. Methods: Using an observational cohort of RA from 2012 to 2021, we collected cross-sectional data of RA patients annually to analyze a trend in RA management. For patients who initiated b/tsDMRDs, we evaluated treatment outcomes between b/tsDMARDs. Mixed-effect models were applied to examine the statistical implications of changes over time in treatment outcomes with a background adjustment. Results: We analyzed annual cross-sectional data from 5070 patients and longitudinal data from 1816 patients in whom b/tsDMARDs were initiated between 2012 and 2021. b/tsDMARD use increased, whereas glucocorticoid use decreased from 2012 to 2021. Disease activity and functional disability measures improved over time. The percentage of tsDMARD prescriptions considerably increased. All b/tsDMARDs showed clinical improvements in disease activity and functional disability. Statistically, TNFi showed better short-term improvements in b/tsDMARD-naïve patients, while IL6Ri demonstrated significant long-term benefits. IL6Ri had better retention rates in switched patients. After adjustment for patient characteristics, the annual change of RA disease activity and functional disability fared significantly better from 2012 to 2021. Conclusions: With the development of new RA therapeutics, overall treatment outcomes advanced in the past decade.","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140715488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52. Methods: BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks. Results: Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%).
{"title":"Birmekizumab: Erweitert die Therapieoptionen besonders bei axialer Spondylarthritis","authors":"P. Sewerin","doi":"10.1159/000538713","DOIUrl":"https://doi.org/10.1159/000538713","url":null,"abstract":"Objectives: Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52. Methods: BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks. Results: Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%).","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":"65 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140713572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
António Marinho, José Delgado Alves, Jorge Fortuna, Raquel Faria, Isabel Almeida, Glória Alves, João Araújo Correia, Ana Campar, Mariana Brandão, Jorge Crespo, Daniela Marado, João Matos-Costa, S. Oliveira, Fernando Salvador, Lelita Santos, Fátima Silva, Milene Fernandes, Carlos Vasconcelos
Systemischer Lupus erythematodes (SLE), das Antiphospholipid-Syndrom (APS) und das Sjögren-Syndrom (SS) sind heterogene Autoimmunerkrankungen. Schwere Ausprägungen sowie Therapieresistenz bzw. -unverträglichkeit gegenüber herkömmlichen Immunsuppressiva erfordern andere Behandlungsoptionen, d.h. biologische Arzneimittel und kleine Moleküle. Unser Ziel war es, evidenz- und praxisbasierte Leitlinien für die zulassungsüberschreitende Anwendung von Biologika bei SLE, APS und SS zu definieren. Die Empfehlungen wurden nach einem umfassenden Literaturreview und 2 Konsensrunden durch ein unabhängiges Expertengremium abgegeben. Das Gremium umfasste 17 Experten für Innere Medizin mit anerkannter Praxis im Bereich der Behandlung von Autoimmunerkrankungen. Die Literaturrecherche erfolgte systematisch für die Jahre von 2014 bis 2019 und wurde später durch Querverweisprüfungen und Experteninformationen bis 2021 aktualisiert. Es wurden vorläufige Empfehlungen von Arbeitsgruppen für jede Krankheit erarbeitet. Ein Revisionsmeeting mit allen Experten fand vor dem Konsensmeeting im Juni 2021 statt. Alle Experten stimmten in 2 Runden ab (stimme zu, stimme nicht zu, stimme weder zu noch widerspreche ich), und Empfehlungen mit mindestens 75% Zustimmung wurden anerkannt. Insgesamt 32 abschließende Empfehlungen (20 für die SLE-, 5 für die APS- und 7 für die SS-Behandlung) wurden von den Experten anerkannt. Diese Empfehlungen berücksichtigen die Organbeteiligung, die Ausprägung, den Schweregrad und das Ansprechen auf frühere Behandlungen. Bei diesen 3 Autoimmunkrankheiten beziehen sich die meisten Empfehlungen auf Rituximab, was auf die höhere Anzahl von Studien und der klinischen Erfahrung mit diesem biologischen Wirkstoff zurückzuführen ist. Eine sequenzielle Behandlung mit Belimumab nach Rituximab kann auch bei schweren Fällen von SLE und SS indiziert sein. Eine Zweitlinientherapie mit Baricitinib, Bortezomib, Eculizumab, Secukinumab oder Tocilizumab kann bei SLE-spezifischen Ausprägungen erwogen werden. Diese evidenz- und praxisbasierten Empfehlungen können die Behandlungsentscheidung unterstützen und letztendlich das Behandlungsergebnis bei Patienten mit SLE, APS oder SS verbessern.
系统性红斑狼疮（SLE）、抗磷脂综合征（APS）和斯约格伦综合征（SS）是一种异质性自身免疫疾病。严重的表现以及对传统免疫抑制剂的耐药性或不耐受性需要其他治疗方案，即生物药物和小分子药物。我们的目标是为系统性红斑狼疮、APS 和 SS 的生物制剂标签外使用制定基于证据和实践的指南。这些建议是由一个独立的专家小组经过全面的文献回顾和两轮共识后提出的。专家组由 17 位在治疗自身免疫性疾病方面具有丰富经验的内科专家组成。文献检索在 2014 年至 2019 年期间系统进行，随后通过交叉引用和专家信息进行更新，直至 2021 年。工作组针对每种疾病制定了初步建议。在 2021 年 6 月召开共识会议之前，与所有专家举行了一次审查会议。所有专家进行了两轮投票（同意、不同意、既不同意也不不同意），同意率至少达到 75% 的建议获得认可。共有 32 项最终建议（20 项针对系统性红斑狼疮、5 项针对 APS、7 项针对 SS 治疗）获得专家认可。这些建议考虑了受累器官、表现、严重程度和对以往治疗的反应。对于这三种自身免疫性疾病，大多数建议都与利妥昔单抗有关，因为这种生物制剂的研究和临床经验较多。在利妥昔单抗治疗后使用贝利木单抗进行序贯治疗也适用于严重的系统性红斑狼疮和SS病例。对于系统性红斑狼疮的特异性表现，可以考虑使用巴利替尼、硼替佐米、依库珠单抗、secukinumab或托珠单抗进行二线治疗。这些以证据和实践为基础的建议可以为系统性红斑狼疮、APS 或 SS 患者的治疗决策提供支持，并最终改善治疗效果。
{"title":"Biologische Therapie bei systemischem Lupus erythematodes, Antiphospholipid-Syndrom und Sjögren-Syndrom: evidenz- und praxisbasierte Leitlinien","authors":"António Marinho, José Delgado Alves, Jorge Fortuna, Raquel Faria, Isabel Almeida, Glória Alves, João Araújo Correia, Ana Campar, Mariana Brandão, Jorge Crespo, Daniela Marado, João Matos-Costa, S. Oliveira, Fernando Salvador, Lelita Santos, Fátima Silva, Milene Fernandes, Carlos Vasconcelos","doi":"10.1159/000538603","DOIUrl":"https://doi.org/10.1159/000538603","url":null,"abstract":"Systemischer Lupus erythematodes (SLE), das Antiphospholipid-Syndrom (APS) und das Sjögren-Syndrom (SS) sind heterogene Autoimmunerkrankungen. Schwere Ausprägungen sowie Therapieresistenz bzw. -unverträglichkeit gegenüber herkömmlichen Immunsuppressiva erfordern andere Behandlungsoptionen, d.h. biologische Arzneimittel und kleine Moleküle. Unser Ziel war es, evidenz- und praxisbasierte Leitlinien für die zulassungsüberschreitende Anwendung von Biologika bei SLE, APS und SS zu definieren. Die Empfehlungen wurden nach einem umfassenden Literaturreview und 2 Konsensrunden durch ein unabhängiges Expertengremium abgegeben. Das Gremium umfasste 17 Experten für Innere Medizin mit anerkannter Praxis im Bereich der Behandlung von Autoimmunerkrankungen. Die Literaturrecherche erfolgte systematisch für die Jahre von 2014 bis 2019 und wurde später durch Querverweisprüfungen und Experteninformationen bis 2021 aktualisiert. Es wurden vorläufige Empfehlungen von Arbeitsgruppen für jede Krankheit erarbeitet. Ein Revisionsmeeting mit allen Experten fand vor dem Konsensmeeting im Juni 2021 statt. Alle Experten stimmten in 2 Runden ab (stimme zu, stimme nicht zu, stimme weder zu noch widerspreche ich), und Empfehlungen mit mindestens 75% Zustimmung wurden anerkannt. Insgesamt 32 abschließende Empfehlungen (20 für die SLE-, 5 für die APS- und 7 für die SS-Behandlung) wurden von den Experten anerkannt. Diese Empfehlungen berücksichtigen die Organbeteiligung, die Ausprägung, den Schweregrad und das Ansprechen auf frühere Behandlungen. Bei diesen 3 Autoimmunkrankheiten beziehen sich die meisten Empfehlungen auf Rituximab, was auf die höhere Anzahl von Studien und der klinischen Erfahrung mit diesem biologischen Wirkstoff zurückzuführen ist. Eine sequenzielle Behandlung mit Belimumab nach Rituximab kann auch bei schweren Fällen von SLE und SS indiziert sein. Eine Zweitlinientherapie mit Baricitinib, Bortezomib, Eculizumab, Secukinumab oder Tocilizumab kann bei SLE-spezifischen Ausprägungen erwogen werden. Diese evidenz- und praxisbasierten Empfehlungen können die Behandlungsentscheidung unterstützen und letztendlich das Behandlungsergebnis bei Patienten mit SLE, APS oder SS verbessern.","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":"9 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140713034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hintergrund: Das Antiphospholipid-Syndrom (APS), das durch thrombotische Ereignisse oder geburtshilfliche Komplikationen bei anhaltend hohen Antiphospholipid-Antikörpern definiert ist, zeichnet sich durch eine Vielzahl von klinischen Erscheinungsformen aus, und die Auswirkungen des Gefäßverschlusses können nahezu jedes Organsystem oder Gewebe betreffen. Da die Klassifizierungskriterien für das APS bei Erwachsenen in der Pädiatrie (wo schwangerschaftsbedingte Probleme selten sind) nicht gut verifiziert sind, ist die Schätzung der Prävalenz im Kindesalter schwierig. Schlaganfall und Lungenembolie sind thromboembolische Ereignisse, die bei Kindern auftreten und eine erhebliche Langzeitmorbidität verursachen können. Kinder mit APS sind anfälliger für wiederkehrende Thromboembolien als Erwachsene. Die kutanen Symptome stehen im Vordergrund und sind in der Regel der erste Hinweis auf ein APS. Obwohl dermatologische Befunde äußerst heterogen sind, ist es wichtig zu überlegen, welche dermatologischen Symptome die Untersuchung auf ein APS und die erforderliche weitere Behandlung rechtfertigen. Falldarstellung: Wir beschreiben einen 7-jährigen iranischen Jungen mit retiformer Purpura und akralen kutanen ischämischen Läsionen als erste klinische Präsentation des APS im Rahmen eines systemischen Lupus erythematodes.
{"title":"Kutanes mikrovaskuläres Okklusionssyndrom als erste Manifestation eines katastrophalen Lupus-assoziierten Antiphospholipid-Antikörper-Syndroms: ein Fallbericht","authors":"Nastaran-Sadat Hosseini, S. Babaei, Hamid Rahimi, Alaleh Gheissari, Banafsheh Sedaghat, Mahsa Pourmahdi-Boroujeni, Bahareh Abtahi-Naeini","doi":"10.1159/000535813","DOIUrl":"https://doi.org/10.1159/000535813","url":null,"abstract":"Hintergrund: Das Antiphospholipid-Syndrom (APS), das durch thrombotische Ereignisse oder geburtshilfliche Komplikationen bei anhaltend hohen Antiphospholipid-Antikörpern definiert ist, zeichnet sich durch eine Vielzahl von klinischen Erscheinungsformen aus, und die Auswirkungen des Gefäßverschlusses können nahezu jedes Organsystem oder Gewebe betreffen. Da die Klassifizierungskriterien für das APS bei Erwachsenen in der Pädiatrie (wo schwangerschaftsbedingte Probleme selten sind) nicht gut verifiziert sind, ist die Schätzung der Prävalenz im Kindesalter schwierig. Schlaganfall und Lungenembolie sind thromboembolische Ereignisse, die bei Kindern auftreten und eine erhebliche Langzeitmorbidität verursachen können. Kinder mit APS sind anfälliger für wiederkehrende Thromboembolien als Erwachsene. Die kutanen Symptome stehen im Vordergrund und sind in der Regel der erste Hinweis auf ein APS. Obwohl dermatologische Befunde äußerst heterogen sind, ist es wichtig zu überlegen, welche dermatologischen Symptome die Untersuchung auf ein APS und die erforderliche weitere Behandlung rechtfertigen. Falldarstellung: Wir beschreiben einen 7-jährigen iranischen Jungen mit retiformer Purpura und akralen kutanen ischämischen Läsionen als erste klinische Präsentation des APS im Rahmen eines systemischen Lupus erythematodes.","PeriodicalId":17887,"journal":{"name":"Kompass Autoimmun","volume":"19 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139525323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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