Pub Date : 2024-08-26DOI: 10.1016/S2665-9913(24)00231-5
George Bertsias , Jinoos Yazdany
{"title":"Achievable but elusive: LLDAS and DORIS remission in clinical trials of belimumab","authors":"George Bertsias , Jinoos Yazdany","doi":"10.1016/S2665-9913(24)00231-5","DOIUrl":"10.1016/S2665-9913(24)00231-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e734-e735"},"PeriodicalIF":15.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1016/S2665-9913(24)00162-0
Ioannis Parodis MD , Julius Lindblom MD , Prof Roger A Levy MD , Margherita Zen MD , Nursen Cetrez MD , Alvaro Gomez MD , Shereen Oon MBBS , Christine Henning PharmD , Prof Munther Khamashta MD , Holly A Quasny PharmD , Deven Chauhan MSc , Prof Anca Askanase MD , Prof Ronald van Vollenhoven MD , Prof Mandana Nikpour MBBS
<div><h3>Background</h3><div>Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE.</div></div><div><h3>Methods</h3><div>In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [<span><span>NCT00410384</span><svg><path></path></svg></span>], BLISS-52 [<span><span>NCT00424476</span><svg><path></path></svg></span>], BLISS-NEA [<span><span>NCT01345253</span><svg><path></path></svg></span>], BLISS-SC [<span><span>NCT01484496</span><svg><path></path></svg></span>], and EMBRACE [<span><span>NCT01632241</span><svg><path></path></svg></span>]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White).</div></div><div><h3>Findings</h3><div>Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28–45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants <em>vs</em> 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15–1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32–52 (week 52: 322 [17%] of 1869 participants <em>vs</em> 125 [10%] of 1217 participants; 1·74 [1·44–2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was signifi
背景：疾病缓解或疾病活动度低是系统性红斑狼疮（SLE）患者的主要治疗目标。贝利木单抗的关键性试验是在引入这些目标之前进行的。在这项研究中，我们旨在汇集各项试验的数据，以评估大量具有种族和文化多样性的系统性红斑狼疮患者达到缓解和低疾病活动度的情况：在这项综合事后分析中，我们汇总了贝利木单抗五项三期试验（BLISS-76 [NCT00410384]、BLISS-52 [NCT00424476]、BLISS-NEA [NCT01345253]、BLISS-SC [NCT01484496]和EMBRACE [NCT01632241]）的数据，这些试验均针对活动性自身抗体阳性系统性红斑狼疮患者。患者被随机分配接受贝利木单抗（每月静脉注射10毫克/千克或每周皮下注射200毫克）或安慰剂以及标准疗法。从第4周到第52周，每隔4周分析一次贝利木单抗与安慰剂的对比情况，采用经试验方差调整的改良泊松回归法，对所有患者以及按系统性红斑狼疮疾病活动指数-2000基线评分（每天7-5毫克）、抗疟药物使用情况（是或否）和种族（黑非洲血统或非裔美国人、亚洲人、土著美国人或白人）划分的亚组进行分析。研究结果：分析了3086名患者（贝利木单抗组1869人，安慰剂组1217人）的数据。3086名患者中有2913名（94%）为女性，173名（6%）为男性，年龄中位数为36岁（IQR为28-45岁）。在第28、48和52周，贝利木单抗组患者的DORIS缓解比例明显高于安慰剂组（第52周：1869名参与者中的148人[8%] vs 1217名参与者中的68人[6%]；风险比1-51 [95% CI 1-15-1-99]；P=0-0055）。在第8、24、32-52周，贝利木单抗组达到LLDAS的患者比例高于安慰剂组（第52周：1869名参与者中的322[17%]对1217名参与者中的125[10%]；1-74 [1-44-2-12]；p解释：在活动性系统性红斑狼疮成人患者中，贝利木单抗联合标准疗法比安慰剂联合标准疗法在获得DORIS缓解（两组均达到较低比例）和LLDAS方面的获益更大，最早在DORIS缓解的第28周和LLDAS的第8周就观察到了差异：瑞典风湿病协会、古斯塔夫五世国王 80 年基金会、瑞典医学会、Nyckelfonden、Nanna Svartz 教授基金会、Ulla 和 Roland Gustafsson 基金会、斯德哥尔摩地区以及卡罗林斯卡医学院。
{"title":"Attainment of remission and low disease activity after treatment with belimumab in patients with systemic lupus erythematosus: a post-hoc analysis of pooled data from five randomised clinical trials","authors":"Ioannis Parodis MD , Julius Lindblom MD , Prof Roger A Levy MD , Margherita Zen MD , Nursen Cetrez MD , Alvaro Gomez MD , Shereen Oon MBBS , Christine Henning PharmD , Prof Munther Khamashta MD , Holly A Quasny PharmD , Deven Chauhan MSc , Prof Anca Askanase MD , Prof Ronald van Vollenhoven MD , Prof Mandana Nikpour MBBS","doi":"10.1016/S2665-9913(24)00162-0","DOIUrl":"10.1016/S2665-9913(24)00162-0","url":null,"abstract":"<div><h3>Background</h3><div>Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE.</div></div><div><h3>Methods</h3><div>In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [<span><span>NCT00410384</span><svg><path></path></svg></span>], BLISS-52 [<span><span>NCT00424476</span><svg><path></path></svg></span>], BLISS-NEA [<span><span>NCT01345253</span><svg><path></path></svg></span>], BLISS-SC [<span><span>NCT01484496</span><svg><path></path></svg></span>], and EMBRACE [<span><span>NCT01632241</span><svg><path></path></svg></span>]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White).</div></div><div><h3>Findings</h3><div>Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28–45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants <em>vs</em> 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15–1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32–52 (week 52: 322 [17%] of 1869 participants <em>vs</em> 125 [10%] of 1217 participants; 1·74 [1·44–2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was signifi","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e751-e761"},"PeriodicalIF":15.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1016/S2665-9913(24)00228-5
Suzanne Arends , Arjan Vissink , Frans G M Kroese , Gwenny M Verstappen , Hendrika Bootsma
{"title":"A future for prediction and treatment of Sjögren's disease-associated lymphomas","authors":"Suzanne Arends , Arjan Vissink , Frans G M Kroese , Gwenny M Verstappen , Hendrika Bootsma","doi":"10.1016/S2665-9913(24)00228-5","DOIUrl":"10.1016/S2665-9913(24)00228-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 10","pages":"Pages e658-e660"},"PeriodicalIF":15.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1016/S2665-9913(24)00187-5
Karl Gisslander , Arthur White PhD , Louis Aslett PhD , Zdenka Hrušková MD PhD , Prof Peter Lamprecht MD , Prof Jacek Musiał MD PhD , Jamsheela Nazeer PhD , James Ng PhD , Prof Declan O'Sullivan PhD , Prof Xavier Puéchal MD PhD , Matthew Rutherford MD , Prof Mårten Segelmark MD PhD , Benjamin Terrier MD PhD , Prof Vladimir Tesař MD PhD , Michelangelo Tesi , Prof Augusto Vaglio MD PhD , Krzysztof Wójcik MD PhD , Prof Mark A Little MD PhD , Aladdin J Mohammad MD PhD , Zdenka Hruskova
<div><h3>Background</h3><div>Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a heterogenous autoimmune disease. While traditionally stratified into two conditions, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the subclassification of ANCA-associated vasculitis is subject to continued debate. Here we aim to identify phenotypically distinct subgroups and develop a data-driven subclassification of ANCA-associated vasculitis, using a large real-world dataset.</div></div><div><h3>Methods</h3><div>In the collaborative data reuse project FAIRVASC (Findable, Accessible, Interoperable, Reusable, Vasculitis), registry records of patients with ANCA-associated vasculitis were retrieved from six European vasculitis registries: the Czech Registry of ANCA-associated vasculitis (Czech Republic), the French Vasculitis Study Group Registry (FVSG; France), the Joint Vasculitis Registry in German-speaking Countries (GeVas; Germany), the Polish Vasculitis Registry (POLVAS; Poland), the Irish Rare Kidney Disease Registry (RKD; Ireland), and the Skåne Vasculitis Cohort (Sweden). We performed model-based clustering of 17 mixed-type clinical variables using a parsimonious mixture of two latent Gaussian variable models. Clinical validation of the optimal cluster solution was made through summary statistics of the clusters' demography, phenotypic and serological characteristics, and outcome. The predictive value of models featuring the cluster affiliations were compared with classifications based on clinical diagnosis and ANCA specificity. People with lived experience were involved throughout the FAIRVASVC project.</div></div><div><h3>Findings</h3><div>A total of 3868 patients diagnosed with ANCA-associated vasculitis between Nov 1, 1966, and March 1, 2023, were included in the study across the six registries (Czech Registry n=371, FVSG n=1780, GeVas n=135, POLVAS n=792, RKD n=439, and Skåne Vasculitis Cohort n=351). There were 2434 (62·9%) patients with GPA and 1434 (37·1%) with MPA. Mean age at diagnosis was 57·2 years (SD 16·4); 2006 (51·9%) of 3867 patients were men and 1861 (48·1%) were women. We identified five clusters, with distinct phenotype, biochemical presentation, and disease outcome. Three clusters were characterised by kidney involvement: one severe kidney cluster (555 [14·3%] of 3868 patients) with high C-reactive protein (CRP) and serum creatinine concentrations, and variable ANCA specificity (SK cluster); one myeloperoxidase (MPO)-ANCA-positive kidney involvement cluster (782 [20·2%]) with limited extrarenal disease (MPO-K cluster); and one proteinase 3 (PR3)-ANCA-positive kidney involvement cluster (683 [17·7%]) with widespread extrarenal disease (PR3-K cluster). Two clusters were characterised by relative absence of kidney involvement: one was a predominantly PR3-ANCA-positive cluster (1202 [31·1%]) with inflammatory multisystem disease (IMS cluster), and one was a cluster (646 [16·7%]) with predominantl
{"title":"Data-driven subclassification of ANCA-associated vasculitis: model-based clustering of a federated international cohort","authors":"Karl Gisslander , Arthur White PhD , Louis Aslett PhD , Zdenka Hrušková MD PhD , Prof Peter Lamprecht MD , Prof Jacek Musiał MD PhD , Jamsheela Nazeer PhD , James Ng PhD , Prof Declan O'Sullivan PhD , Prof Xavier Puéchal MD PhD , Matthew Rutherford MD , Prof Mårten Segelmark MD PhD , Benjamin Terrier MD PhD , Prof Vladimir Tesař MD PhD , Michelangelo Tesi , Prof Augusto Vaglio MD PhD , Krzysztof Wójcik MD PhD , Prof Mark A Little MD PhD , Aladdin J Mohammad MD PhD , Zdenka Hruskova","doi":"10.1016/S2665-9913(24)00187-5","DOIUrl":"10.1016/S2665-9913(24)00187-5","url":null,"abstract":"<div><h3>Background</h3><div>Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a heterogenous autoimmune disease. While traditionally stratified into two conditions, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the subclassification of ANCA-associated vasculitis is subject to continued debate. Here we aim to identify phenotypically distinct subgroups and develop a data-driven subclassification of ANCA-associated vasculitis, using a large real-world dataset.</div></div><div><h3>Methods</h3><div>In the collaborative data reuse project FAIRVASC (Findable, Accessible, Interoperable, Reusable, Vasculitis), registry records of patients with ANCA-associated vasculitis were retrieved from six European vasculitis registries: the Czech Registry of ANCA-associated vasculitis (Czech Republic), the French Vasculitis Study Group Registry (FVSG; France), the Joint Vasculitis Registry in German-speaking Countries (GeVas; Germany), the Polish Vasculitis Registry (POLVAS; Poland), the Irish Rare Kidney Disease Registry (RKD; Ireland), and the Skåne Vasculitis Cohort (Sweden). We performed model-based clustering of 17 mixed-type clinical variables using a parsimonious mixture of two latent Gaussian variable models. Clinical validation of the optimal cluster solution was made through summary statistics of the clusters' demography, phenotypic and serological characteristics, and outcome. The predictive value of models featuring the cluster affiliations were compared with classifications based on clinical diagnosis and ANCA specificity. People with lived experience were involved throughout the FAIRVASVC project.</div></div><div><h3>Findings</h3><div>A total of 3868 patients diagnosed with ANCA-associated vasculitis between Nov 1, 1966, and March 1, 2023, were included in the study across the six registries (Czech Registry n=371, FVSG n=1780, GeVas n=135, POLVAS n=792, RKD n=439, and Skåne Vasculitis Cohort n=351). There were 2434 (62·9%) patients with GPA and 1434 (37·1%) with MPA. Mean age at diagnosis was 57·2 years (SD 16·4); 2006 (51·9%) of 3867 patients were men and 1861 (48·1%) were women. We identified five clusters, with distinct phenotype, biochemical presentation, and disease outcome. Three clusters were characterised by kidney involvement: one severe kidney cluster (555 [14·3%] of 3868 patients) with high C-reactive protein (CRP) and serum creatinine concentrations, and variable ANCA specificity (SK cluster); one myeloperoxidase (MPO)-ANCA-positive kidney involvement cluster (782 [20·2%]) with limited extrarenal disease (MPO-K cluster); and one proteinase 3 (PR3)-ANCA-positive kidney involvement cluster (683 [17·7%]) with widespread extrarenal disease (PR3-K cluster). Two clusters were characterised by relative absence of kidney involvement: one was a predominantly PR3-ANCA-positive cluster (1202 [31·1%]) with inflammatory multisystem disease (IMS cluster), and one was a cluster (646 [16·7%]) with predominantl","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 11","pages":"Pages e762-e770"},"PeriodicalIF":15.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1016/S2665-9913(24)00183-8
Andreas V Goules PhD , Loukas Chatzis PhD , Vasilis C Pezoulas PhD , Markos Patsouras PhD , Prof Clio Mavragani PhD , Prof Luca Quartuccio PhD , Prof Chiara Baldini PhD , Prof Salvatore De Vita PhD , Prof Dimitrios I Fotiadis PhD , Prof Athanasios G Tzioufas PhD
<div><h3>Background</h3><div>Non-Hodgkin lymphomas have a substantial impact on individuals with Sjögren's disease. This study focuses on mucosal-associated lymphoid tissue (MALT) lymphomas, which constitute the majority of Sjögren's disease-associated non-Hodgkin lymphomas. We aimed to identify reliable lymphoma predictors in patients with Sjögren's disease and study their progression over time.</div></div><div><h3>Methods</h3><div>In this case-control study, patients diagnosed with Sjögren's disease-associated MALT lymphoma, with a minimum of 3 years between Sjögren's disease diagnosis and MALT lymphoma diagnosis, were included from three centres specialising in Sjögren's disease (University of Athens, Athens, Greece; University of Pisa, Pisa, Italy; and University of Udine, Udine, Italy) and matched 1:1 with control participants with Sjögren's disease who did not have lymphoma according to age, sex, disease duration at last follow up, and treatment modality. Three harmonised datasets were constructed, curated, and analysed to identify MALT lymphoma predictors, representing three distinct timepoints in lymphomagenesis progression: V1 at Sjögren's disease diagnosis, V2 3–4 years before lymphoma diagnosis, and V3 0·5–1·5 years before lymphoma diagnosis. All recruited patients fulfilled the 2016 American College of Rheumatology–European League Against Rheumatism criteria for Sjögren's disease. The primary outcome was to identify MALT lymphoma predictors in Sjögren's disease, present at the timepoint of Sjögren's disease diagnosis and 3–4 years before the diagnosis of MALT lymphoma. A fast correlation-based feature selection and logistic regression model was used at V1 and V2 to identify MALT lymphoma predictors. The progression of potential predictors was studied across V1, V2, and V3. Histological parameters were not included in the analysis. An individual with lived experience of Sjögren's disease was involved in the study design.</div></div><div><h3>Findings</h3><div>80 patients with Sjögren's disease-associated MALT lymphoma were included in the V1 dataset, 68 in the V2 dataset, and 80 in the V3 dataset, and matched to control participants with Sjögren's disease who did not have lymphoma. In both groups, 72 (90%) of 80 participants were women and eight (10%) were men. The mean age at Sjögren's disease diagnosis was 48·6 years (SD 11·6) in the lymphoma group and 48·7 years (11·5) in the control group. All patients were White, with 88 (55%) of 160 individuals of Greek nationality and 72 (45%) of Italian nationality. At the V1 timepoint, rheumatoid factor was the only independent lymphoma predictor (odds ratio 3·33 [95% CI 1·96–5·64]). At the V2 timepoint, rheumatoid factor (3·66 [95% CI 2·08–6·42]) and European League Against Rheumatism Sjögren's Syndrome Disease Activity Index ≥5 (3·88 [1·69–8·90]) were identified as independent lymphoma risk factors. The high disease activity during the transition from the V1 to V2 timepoint was attributed to
{"title":"Identification and evolution of predictors of Sjögren's disease-associated mucosa-associated lymphoid tissue lymphoma development over time: a case-control study","authors":"Andreas V Goules PhD , Loukas Chatzis PhD , Vasilis C Pezoulas PhD , Markos Patsouras PhD , Prof Clio Mavragani PhD , Prof Luca Quartuccio PhD , Prof Chiara Baldini PhD , Prof Salvatore De Vita PhD , Prof Dimitrios I Fotiadis PhD , Prof Athanasios G Tzioufas PhD","doi":"10.1016/S2665-9913(24)00183-8","DOIUrl":"10.1016/S2665-9913(24)00183-8","url":null,"abstract":"<div><h3>Background</h3><div>Non-Hodgkin lymphomas have a substantial impact on individuals with Sjögren's disease. This study focuses on mucosal-associated lymphoid tissue (MALT) lymphomas, which constitute the majority of Sjögren's disease-associated non-Hodgkin lymphomas. We aimed to identify reliable lymphoma predictors in patients with Sjögren's disease and study their progression over time.</div></div><div><h3>Methods</h3><div>In this case-control study, patients diagnosed with Sjögren's disease-associated MALT lymphoma, with a minimum of 3 years between Sjögren's disease diagnosis and MALT lymphoma diagnosis, were included from three centres specialising in Sjögren's disease (University of Athens, Athens, Greece; University of Pisa, Pisa, Italy; and University of Udine, Udine, Italy) and matched 1:1 with control participants with Sjögren's disease who did not have lymphoma according to age, sex, disease duration at last follow up, and treatment modality. Three harmonised datasets were constructed, curated, and analysed to identify MALT lymphoma predictors, representing three distinct timepoints in lymphomagenesis progression: V1 at Sjögren's disease diagnosis, V2 3–4 years before lymphoma diagnosis, and V3 0·5–1·5 years before lymphoma diagnosis. All recruited patients fulfilled the 2016 American College of Rheumatology–European League Against Rheumatism criteria for Sjögren's disease. The primary outcome was to identify MALT lymphoma predictors in Sjögren's disease, present at the timepoint of Sjögren's disease diagnosis and 3–4 years before the diagnosis of MALT lymphoma. A fast correlation-based feature selection and logistic regression model was used at V1 and V2 to identify MALT lymphoma predictors. The progression of potential predictors was studied across V1, V2, and V3. Histological parameters were not included in the analysis. An individual with lived experience of Sjögren's disease was involved in the study design.</div></div><div><h3>Findings</h3><div>80 patients with Sjögren's disease-associated MALT lymphoma were included in the V1 dataset, 68 in the V2 dataset, and 80 in the V3 dataset, and matched to control participants with Sjögren's disease who did not have lymphoma. In both groups, 72 (90%) of 80 participants were women and eight (10%) were men. The mean age at Sjögren's disease diagnosis was 48·6 years (SD 11·6) in the lymphoma group and 48·7 years (11·5) in the control group. All patients were White, with 88 (55%) of 160 individuals of Greek nationality and 72 (45%) of Italian nationality. At the V1 timepoint, rheumatoid factor was the only independent lymphoma predictor (odds ratio 3·33 [95% CI 1·96–5·64]). At the V2 timepoint, rheumatoid factor (3·66 [95% CI 2·08–6·42]) and European League Against Rheumatism Sjögren's Syndrome Disease Activity Index ≥5 (3·88 [1·69–8·90]) were identified as independent lymphoma risk factors. The high disease activity during the transition from the V1 to V2 timepoint was attributed to ","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 10","pages":"Pages e693-e702"},"PeriodicalIF":15.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Background</h3><div>Sjögren's disease is the autoimmune disease with the highest risk of lymphoma development. There is no consensus on the optimal way to manage Sjögren's disease complicated by lymphoma. We aimed to describe characteristics, therapeutic strategies, and outcomes of non-Hodgkin lymphoma associated with Sjögren's disease, and their effect on lymphoma and Sjögren's disease prognoses.</div></div><div><h3>Methods</h3><div>We did a multicentre, retrospective, observational study including patients with Sjögren's disease according to the 2016 American College of Rheumatology–European League Against Rheumatism criteria who did not fulfil diagnostic criteria for other connective tissue diseases. We included patients with a lymphoma diagnosis made before Jan 1, 2020, from two expert centres in Paris (France); from the French, multicentre, prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome cohort; and via practitioners registered with the Club Rhumatismes et Inflammation. Using inverse probability of treatment weighting, the effect of lymphoma treatment was compared in relation to three endpoints: lymphoma progression-free survival, new Sjögren's disease systemic activity, and overall survival. Exploratory analyses also aimed to identify factors associated with lymphoma relapse, new Sjögren's disease systemic activity, and overall survival. People with lived experience were not involved in this research.</div></div><div><h3>Findings</h3><div>106 patients with Sjögren's disease who developed lymphoma were included in the study. The most frequent histological subtype was mucosa-associated lymphoid tissue lymphoma (68 [64%] of 106 patients), followed by other marginal zone subtypes (14 [13%] of 106 patients) and diffuse large B-cell lymphoma (14 [13%] of 106 patients). Among the 82 patients with marginal zone lymphoma (72 [88%] women and ten (12%) men; mean age at lymphoma diagnosis 57·5 years [SD 14·8]), multivariable analysis showed that pulmonary localisation was associated with mortality (hazard ratio [HR] 7·92 [95% CI 1·70–37·0]). A watch and wait approach was proposed in 19 (23%) of 82 patients with marginal zone lymphoma, 13 (16%) had first-line localised treatment (surgery or radiotherapy), and 50 (61%) had first-line systemic treatment. After a median follow-up of 7 years, 26 patients (32%) had lymphoma relapse, nine (11%) died, and 27 (33%) had new Sjögren's disease systemic activity. After inverse probability of treatment weighting, patients with systemic treatment at lymphoma diagnosis had a reduced risk of new Sjögren's disease activity (HR 0·43 [95% CI 0·21–0·90]). When comparing patients treated with a combination of chemotherapy and anti-CD20 therapy (n=32) with patients treated with monotherapy (n=18) as a first-line therapy for lymphoma, lymphoma-progression-free survival was improved in patients treated with combination therapy (HR 0·36 [95% CI 0·14–0·94]). The were no differences in new Sj
背景：斯约格伦病是淋巴瘤发病风险最高的自身免疫性疾病。对于治疗并发淋巴瘤的斯约戈伦病的最佳方法，目前尚无共识。我们旨在描述与斯约戈伦病相关的非霍奇金淋巴瘤的特征、治疗策略和结果，以及它们对淋巴瘤和斯约戈伦病预后的影响：我们进行了一项多中心、回顾性、观察性研究，纳入了根据2016年美国风湿病学会-欧洲抗风湿联盟标准确诊的、不符合其他结缔组织疾病诊断标准的斯约戈伦病患者。我们纳入了在 2020 年 1 月 1 日前确诊为淋巴瘤的患者，这些患者来自法国巴黎的两个专家中心、法国多中心前瞻性斯约格伦综合征系统体征和演变评估队列，以及在风湿与炎症俱乐部注册的执业医师。采用逆治疗概率加权法，比较了淋巴瘤治疗效果与三个终点的关系：淋巴瘤无进展生存期、新的斯约格伦病全身活动度和总生存期。探索性分析还旨在确定与淋巴瘤复发、新发斯约格伦病全身活动性和总生存期相关的因素。有生活经验的人没有参与这项研究：研究共纳入了 106 名罹患淋巴瘤的斯约格伦病患者。最常见的组织学亚型是粘膜相关淋巴组织淋巴瘤（106 例患者中有 68 例[64%]），其次是其他边缘区亚型（106 例患者中有 14 例[13%]）和弥漫大 B 细胞淋巴瘤（106 例患者中有 14 例[13%]）。在82名边缘区淋巴瘤患者中（女性72人[88%]，男性10人[12%]；淋巴瘤确诊时的平均年龄为57-5岁[SD 14-8]），多变量分析显示，肺部定位与死亡率有关（危险比[HR] 7-92 [95% CI 1-70-37-0]）。在82名边缘区淋巴瘤患者中，有19人（23%）采用了观察和等待的方法，13人（16%）接受了一线局部治疗（手术或放疗），50人（61%）接受了一线系统治疗。中位随访7年后，26名患者（32%）淋巴瘤复发，9名患者（11%）死亡，27名患者（33%）出现新的系统性活动。在对治疗概率进行反向加权后，淋巴瘤确诊时接受系统治疗的患者出现新的斯约格伦病活动的风险降低（HR 0-43 [95% CI 0-21-0-90]）。将接受化疗和抗CD20联合疗法治疗的患者（32人）与接受单一疗法治疗的患者（18人）作为淋巴瘤一线疗法进行比较，发现接受联合疗法治疗的患者淋巴瘤无进展生存期有所改善（HR 0-36 [95% CI 0-14-0-94]）。联合疗法与单一疗法在新的斯约格伦病全身活动性或总生存率方面没有差异：解读：与局部治疗或观察和等待策略相比，对斯约格伦病相关淋巴瘤采取全身治疗策略可降低新的斯约格伦病全身活动性风险，而联合治疗与降低淋巴瘤复发风险相关：无。
{"title":"Treatment modalities of marginal zone lymphoma and overall survival, haematological response, and underlying Sjögren's disease activity: a multicentre, retrospective, observational study","authors":"Juliette Rocca MD , Maxime Beydon MD , Véronique Le Guern MD , Prof Eric Hachulla PhD , Marion Couderc MD , Sandrine Jousse-Joulin MD , Prof Valérie Devauchelle-Pensec PhD , Prof Jacques-Eric Gottenberg PhD , Prof Olivier Vittecoq PhD , Christian Lavigne MD PhD , Jean Schmidt MD PhD , Claire Larroche MD , Prof Xavier Mariette PhD , Prof Raphaèle Seror PhD , Prof Gaetane Nocturne PhD","doi":"10.1016/S2665-9913(24)00198-X","DOIUrl":"10.1016/S2665-9913(24)00198-X","url":null,"abstract":"<div><h3>Background</h3><div>Sjögren's disease is the autoimmune disease with the highest risk of lymphoma development. There is no consensus on the optimal way to manage Sjögren's disease complicated by lymphoma. We aimed to describe characteristics, therapeutic strategies, and outcomes of non-Hodgkin lymphoma associated with Sjögren's disease, and their effect on lymphoma and Sjögren's disease prognoses.</div></div><div><h3>Methods</h3><div>We did a multicentre, retrospective, observational study including patients with Sjögren's disease according to the 2016 American College of Rheumatology–European League Against Rheumatism criteria who did not fulfil diagnostic criteria for other connective tissue diseases. We included patients with a lymphoma diagnosis made before Jan 1, 2020, from two expert centres in Paris (France); from the French, multicentre, prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome cohort; and via practitioners registered with the Club Rhumatismes et Inflammation. Using inverse probability of treatment weighting, the effect of lymphoma treatment was compared in relation to three endpoints: lymphoma progression-free survival, new Sjögren's disease systemic activity, and overall survival. Exploratory analyses also aimed to identify factors associated with lymphoma relapse, new Sjögren's disease systemic activity, and overall survival. People with lived experience were not involved in this research.</div></div><div><h3>Findings</h3><div>106 patients with Sjögren's disease who developed lymphoma were included in the study. The most frequent histological subtype was mucosa-associated lymphoid tissue lymphoma (68 [64%] of 106 patients), followed by other marginal zone subtypes (14 [13%] of 106 patients) and diffuse large B-cell lymphoma (14 [13%] of 106 patients). Among the 82 patients with marginal zone lymphoma (72 [88%] women and ten (12%) men; mean age at lymphoma diagnosis 57·5 years [SD 14·8]), multivariable analysis showed that pulmonary localisation was associated with mortality (hazard ratio [HR] 7·92 [95% CI 1·70–37·0]). A watch and wait approach was proposed in 19 (23%) of 82 patients with marginal zone lymphoma, 13 (16%) had first-line localised treatment (surgery or radiotherapy), and 50 (61%) had first-line systemic treatment. After a median follow-up of 7 years, 26 patients (32%) had lymphoma relapse, nine (11%) died, and 27 (33%) had new Sjögren's disease systemic activity. After inverse probability of treatment weighting, patients with systemic treatment at lymphoma diagnosis had a reduced risk of new Sjögren's disease activity (HR 0·43 [95% CI 0·21–0·90]). When comparing patients treated with a combination of chemotherapy and anti-CD20 therapy (n=32) with patients treated with monotherapy (n=18) as a first-line therapy for lymphoma, lymphoma-progression-free survival was improved in patients treated with combination therapy (HR 0·36 [95% CI 0·14–0·94]). The were no differences in new Sj","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 10","pages":"Pages e703-e712"},"PeriodicalIF":15.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.1016/S2665-9913(24)00245-5
The Lancet Rheumatology
{"title":"Advancing research and equity through collaboration","authors":"The Lancet Rheumatology","doi":"10.1016/S2665-9913(24)00245-5","DOIUrl":"10.1016/S2665-9913(24)00245-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 9","pages":"Page e587"},"PeriodicalIF":15.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1016/S2665-9913(24)00184-X
Grégoire Martin de Frémont , Jane E Salmon , Nathalie Costedoat-Chalumeau
{"title":"Pregnancy outcome predictors in systemic lupus erythematosus: prospective for brighter perspectives","authors":"Grégoire Martin de Frémont , Jane E Salmon , Nathalie Costedoat-Chalumeau","doi":"10.1016/S2665-9913(24)00184-X","DOIUrl":"10.1016/S2665-9913(24)00184-X","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"6 10","pages":"Pages e654-e655"},"PeriodicalIF":15.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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