Pub Date : 2024-06-01Epub Date: 2024-03-20DOI: 10.1007/s40744-024-00653-6
Joshua F Baker, Catherine Bakewell, Ara Dikranian, Gordon Lam, Jacqueline O'Brien, Page C Moore, Miao Yu, Peter Hur, Karim R Masri
Introduction: Real-world studies describing biosimilar initiation or switching in patients with rheumatoid arthritis (RA) are limited. The aim of this study was to assess treatment patterns and effectiveness of real-world patients with RA initiating infliximab biosimilar IFX-dyyb (CT-P13; Inflectra®) in the USA.
Methods: This observational study evaluated patients with RA from the CorEvitas RA Registry who initiated IFX-dyyb and had Clinical Disease Activity Index (CDAI) recorded at baseline and 6 months. The primary outcome was reaching low disease activity (LDA; CDAI ≤ 10) at 6 months in patients with moderate or high disease activity (CDAI > 10) at baseline. Secondary outcomes were change at 6 months in CDAI and certain patient-reported outcomes (PROs). Patient data were stratified by prior treatment: biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD)-naïve, reference infliximab (IFX-REF) or IFX biosimilar, or a non-IFX biologic or tsDMARD.
Results: Of 318 patients initiating IFX-dyyb, 176 had baseline and 6-month CDAI scores; 73 (41%) switched from IFX, 61 (35%) switched from another non-IFX/biologic/tsDMARD, 32 (18%) were naïve to biologics/tsDMARDs, and 10 (6%) switched from an IFX biosimilar. Among patients with moderate or high disease activity at baseline, 32.9% (95% CI 22.9, 42.9) achieved LDA at 6 months. Mean 6-month change from baseline in CDAI was - 1.8 (95% CI - 3.3, - 0.3) overall; - 4.7 (- 7.6, - 1.7) in patients who switched from a non-IFX biologic/tsDMARD, - 4.1 (- 7.8, - 0.3) in biologic/tsDMARD-naïve patients, and 1.1 (- 0.4, 2.6) in patients who switched from IFX-REF/IFX biosimilar. Other clinical outcomes/PROs improved at 6 months. Of the IFX-dyyb initiators, 68% remained on IFX-dyyb at 6 months.
Conclusion: In this real-world population of patients with RA initiating IFX-dyyb, the majority switched from IFX-REF or a non-IFX biologic/tsDMARD. CDAI remained stable in patients switching from IFX-REF/IFX biosimilar and improved in patients switching from a non-IFX biologic/tsDMARD and in biologic/tsDMARD-naïve patients.
{"title":"Characteristics and 6-Month Outcomes in Patients with Rheumatoid Arthritis Initiating Infliximab Biosimilar IFX-dyyb in a Real-World Setting.","authors":"Joshua F Baker, Catherine Bakewell, Ara Dikranian, Gordon Lam, Jacqueline O'Brien, Page C Moore, Miao Yu, Peter Hur, Karim R Masri","doi":"10.1007/s40744-024-00653-6","DOIUrl":"10.1007/s40744-024-00653-6","url":null,"abstract":"<p><strong>Introduction: </strong>Real-world studies describing biosimilar initiation or switching in patients with rheumatoid arthritis (RA) are limited. The aim of this study was to assess treatment patterns and effectiveness of real-world patients with RA initiating infliximab biosimilar IFX-dyyb (CT-P13; Inflectra<sup>®</sup>) in the USA.</p><p><strong>Methods: </strong>This observational study evaluated patients with RA from the CorEvitas RA Registry who initiated IFX-dyyb and had Clinical Disease Activity Index (CDAI) recorded at baseline and 6 months. The primary outcome was reaching low disease activity (LDA; CDAI ≤ 10) at 6 months in patients with moderate or high disease activity (CDAI > 10) at baseline. Secondary outcomes were change at 6 months in CDAI and certain patient-reported outcomes (PROs). Patient data were stratified by prior treatment: biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD)-naïve, reference infliximab (IFX-REF) or IFX biosimilar, or a non-IFX biologic or tsDMARD.</p><p><strong>Results: </strong>Of 318 patients initiating IFX-dyyb, 176 had baseline and 6-month CDAI scores; 73 (41%) switched from IFX, 61 (35%) switched from another non-IFX/biologic/tsDMARD, 32 (18%) were naïve to biologics/tsDMARDs, and 10 (6%) switched from an IFX biosimilar. Among patients with moderate or high disease activity at baseline, 32.9% (95% CI 22.9, 42.9) achieved LDA at 6 months. Mean 6-month change from baseline in CDAI was - 1.8 (95% CI - 3.3, - 0.3) overall; - 4.7 (- 7.6, - 1.7) in patients who switched from a non-IFX biologic/tsDMARD, - 4.1 (- 7.8, - 0.3) in biologic/tsDMARD-naïve patients, and 1.1 (- 0.4, 2.6) in patients who switched from IFX-REF/IFX biosimilar. Other clinical outcomes/PROs improved at 6 months. Of the IFX-dyyb initiators, 68% remained on IFX-dyyb at 6 months.</p><p><strong>Conclusion: </strong>In this real-world population of patients with RA initiating IFX-dyyb, the majority switched from IFX-REF or a non-IFX biologic/tsDMARD. CDAI remained stable in patients switching from IFX-REF/IFX biosimilar and improved in patients switching from a non-IFX biologic/tsDMARD and in biologic/tsDMARD-naïve patients.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-02DOI: 10.1007/s40744-024-00650-9
Beatriz Frade-Sosa, Andrés Ponce, Estíbaliz Ruiz-Ortiz, Noemí De Moner, María J Gómara, Ana Belén Azuaga, Juan C Sarmiento-Monroy, Rosa Morlà, Virginia Ruiz-Esquide, Laura Macías, Nuria Sapena, Lola Tobalina, Julio Ramirez, Juan D Cañete, Jordi Yague, Josep M Auge, José A Gomez-Puerta, Odette Viñas, Isabel Haro, Raimon Sanmarti
Introduction: This study assesses the accuracy of neutrophil activation markers, including neutrophil extracellular traps (NETs) and calprotectin, as biomarkers of disease activity in patients with established rheumatoid arthritis (RA). We also analyse the relationship between NETs and various types of therapies as well as their association with autoimmunity.
Methods: Observational cross-sectional study of patients with RA receiving treatment with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (JAK-inhibitors) for at least 3 months. Plasma calprotectin levels were measured using an enzyme-linked immunosorbent assay test kit and NETs by measuring their remnants in plasma (neutrophil elastase-DNA and histone-DNA complexes). We also assessed clinical disease activity, joint ultrasound findings and autoantibody status [reumatoid factor (RF), anti-citrullinated peptide/protein antibodies (ACPAs) and anti-carbamylated protein (anti-CarP)]. Associations between neutrophilic biomarkers and clinical or ultrasound scores were sought using correlation analysis. The discriminatory capacity of both neutrophilic biomarkers to detect ultrasound synovitis was analysed through receiver-operating characteristic (ROC) curves.
Results: One hundred fourteen patients were included. Two control groups were included to compare NET levels. The active control group consisted of 15 patients. The second control group consisted of 30 healthy subjects. Plasma NET levels did not correlate with clinical disease status, regardless of the clinic index analysed or the biological therapy administered. No significant correlation was observed between NET remnants and ultrasound synovitis. There was no correlation between plasma NET and autoantibodies. In contrast, plasma calprotectin positively correlated with clinical parameters (swollen joint count [SJC] rho = 0.49; P < 0.001, Clinical Disease Activity Index [CDAI] rho = 0.30; P < 0.001) and ultrasound parameters (rho > 0.50; P < 0.001). Notably, this correlation was stronger than that observed with acute phase reactants.
Conclusion: While NET formation induced by neutrophils may play a role in RA pathogenesis, our study raises questions about the utility of NET remnants in peripheral circulation as a biomarker for inflammatory activity. In contrast, this study strongly supports the usefulness of calprotectin as a biomarker of inflammatory activity in patients with RA.
{"title":"Neutrophilic Activity Biomarkers (Plasma Neutrophil Extracellular Traps and Calprotectin) in Established Patients with Rheumatoid Arthritis Receiving Biological or JAK Inhibitors: A Clinical and Ultrasonographic Study.","authors":"Beatriz Frade-Sosa, Andrés Ponce, Estíbaliz Ruiz-Ortiz, Noemí De Moner, María J Gómara, Ana Belén Azuaga, Juan C Sarmiento-Monroy, Rosa Morlà, Virginia Ruiz-Esquide, Laura Macías, Nuria Sapena, Lola Tobalina, Julio Ramirez, Juan D Cañete, Jordi Yague, Josep M Auge, José A Gomez-Puerta, Odette Viñas, Isabel Haro, Raimon Sanmarti","doi":"10.1007/s40744-024-00650-9","DOIUrl":"10.1007/s40744-024-00650-9","url":null,"abstract":"<p><strong>Introduction: </strong>This study assesses the accuracy of neutrophil activation markers, including neutrophil extracellular traps (NETs) and calprotectin, as biomarkers of disease activity in patients with established rheumatoid arthritis (RA). We also analyse the relationship between NETs and various types of therapies as well as their association with autoimmunity.</p><p><strong>Methods: </strong>Observational cross-sectional study of patients with RA receiving treatment with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (JAK-inhibitors) for at least 3 months. Plasma calprotectin levels were measured using an enzyme-linked immunosorbent assay test kit and NETs by measuring their remnants in plasma (neutrophil elastase-DNA and histone-DNA complexes). We also assessed clinical disease activity, joint ultrasound findings and autoantibody status [reumatoid factor (RF), anti-citrullinated peptide/protein antibodies (ACPAs) and anti-carbamylated protein (anti-CarP)]. Associations between neutrophilic biomarkers and clinical or ultrasound scores were sought using correlation analysis. The discriminatory capacity of both neutrophilic biomarkers to detect ultrasound synovitis was analysed through receiver-operating characteristic (ROC) curves.</p><p><strong>Results: </strong>One hundred fourteen patients were included. Two control groups were included to compare NET levels. The active control group consisted of 15 patients. The second control group consisted of 30 healthy subjects. Plasma NET levels did not correlate with clinical disease status, regardless of the clinic index analysed or the biological therapy administered. No significant correlation was observed between NET remnants and ultrasound synovitis. There was no correlation between plasma NET and autoantibodies. In contrast, plasma calprotectin positively correlated with clinical parameters (swollen joint count [SJC] rho = 0.49; P < 0.001, Clinical Disease Activity Index [CDAI] rho = 0.30; P < 0.001) and ultrasound parameters (rho > 0.50; P < 0.001). Notably, this correlation was stronger than that observed with acute phase reactants.</p><p><strong>Conclusion: </strong>While NET formation induced by neutrophils may play a role in RA pathogenesis, our study raises questions about the utility of NET remnants in peripheral circulation as a biomarker for inflammatory activity. In contrast, this study strongly supports the usefulness of calprotectin as a biomarker of inflammatory activity in patients with RA.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-04DOI: 10.1007/s40744-024-00649-2
Piero Ruscitti, Giulia Cataldi, Martina Gentile, Alice Dionisi, Paola Volpe, Annacarla Finucci, Lucrezia Verardi, Claudia Di Muzio, Noemi Italiano, Eleonora Celletti, Myriam Di Penta, Ilenia Di Cola, Alessandra Marrelli, Alessia Alfonsi, Francesco Delle Monache, Francesco Cipollone, Marco Gabini, Paola Cipriani
Introduction: Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in patients with PsA in a "real-life" multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up.
Methods: Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6 months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR.
Results: A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5 years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6 months, a significant reduction of DAPSA was observed (β - 15.47, p = 0.001, 95% CI - 23.15 to - 9.79) with 39.6% of patients achieving a DAPSA ≤ 14. At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1 months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs.
Conclusion: The "real-life" 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18 months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs.
{"title":"The Evaluation of Effectiveness and Safety of Guselkumab in Patients with Psoriatic Arthritis in a Prospective Multicentre \"Real-Life\" Cohort Study.","authors":"Piero Ruscitti, Giulia Cataldi, Martina Gentile, Alice Dionisi, Paola Volpe, Annacarla Finucci, Lucrezia Verardi, Claudia Di Muzio, Noemi Italiano, Eleonora Celletti, Myriam Di Penta, Ilenia Di Cola, Alessandra Marrelli, Alessia Alfonsi, Francesco Delle Monache, Francesco Cipollone, Marco Gabini, Paola Cipriani","doi":"10.1007/s40744-024-00649-2","DOIUrl":"10.1007/s40744-024-00649-2","url":null,"abstract":"<p><strong>Introduction: </strong>Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in patients with PsA in a \"real-life\" multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up.</p><p><strong>Methods: </strong>Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6 months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR.</p><p><strong>Results: </strong>A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5 years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6 months, a significant reduction of DAPSA was observed (β - 15.47, p = 0.001, 95% CI - 23.15 to - 9.79) with 39.6% of patients achieving a DAPSA ≤ 14. At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1 months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs.</p><p><strong>Conclusion: </strong>The \"real-life\" 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18 months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-18DOI: 10.1007/s40744-024-00658-1
Roy Fleischmann, Ricardo Blanco, Filip Van den Bosch, Louis Bessette, Yanna Song, Sara K Penn, Erin McDearmon-Blondell, Nasser Khan, Kelly Chan, Eduardo Mysler
Introduction: This study aimed to describe the long-term efficacy and safety of upadacitinib and adalimumab through 228 weeks following immediate switch to the alternate therapy with a different mechanism of action (MoA) in patients with rheumatoid arthritis (RA) not achieving treatment goals with their initial randomized therapy in the ongoing phase 3 SELECT-COMPARE study.
Methods: Patients with non-response or incomplete response to initially prescribed upadacitinib 15 mg once daily or adalimumab 40 mg every other week were switched to the alternate therapy by week 26. Efficacy was evaluated through 228 weeks post-switch using validated outcome measures, including Clinical Disease Activity Index (CDAI) low disease activity (LDA; ≤ 10)/remission (≤ 2.8); 28-joint Disease Activity Score based on C-reactive protein ≤ 3.2/< 2.6; ≥ 20%/50%/70% improvement in American College of Rheumatology (ACR) response criteria; and change from baseline in ACR core components. Data are reported as observed. Safety was assessed by treatment-emergent adverse events (TEAEs) through week 264.
Results: Of patients initially randomized to upadacitinib and adalimumab, 38.7% and 48.6%, respectively, switched to the alternate therapy by week 26. Clinically relevant improvements in all efficacy measures were observed through 228 weeks post-switch and were generally similar between groups, with small numeric differences mostly in favor of switching to upadacitinib. CDAI remission was achieved by 32.7% and 28.6% of initial non-responders, and 27.5% and 27.3% of incomplete responders, while CDAI LDA was achieved by 76.9% and 72.9% of non-responders, and 72.5% and 72.7% of incomplete responders switching to upadacitinib and to adalimumab, respectively. TEAE rates were similar between groups, although herpes zoster infection, lymphopenia, and creatine phosphokinase elevation were more frequent when switching to upadacitinib. No new safety signals were identified.
Conclusion: Switching to a different MoA may provide long-term benefit to patients with RA not achieving treatment goals with their initial therapy, with acceptable safety profiles.
{"title":"Long-term Efficacy and Safety Following Switch Between Upadacitinib and Adalimumab in Patients with Rheumatoid Arthritis: 5-Year Data from SELECT-COMPARE.","authors":"Roy Fleischmann, Ricardo Blanco, Filip Van den Bosch, Louis Bessette, Yanna Song, Sara K Penn, Erin McDearmon-Blondell, Nasser Khan, Kelly Chan, Eduardo Mysler","doi":"10.1007/s40744-024-00658-1","DOIUrl":"10.1007/s40744-024-00658-1","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to describe the long-term efficacy and safety of upadacitinib and adalimumab through 228 weeks following immediate switch to the alternate therapy with a different mechanism of action (MoA) in patients with rheumatoid arthritis (RA) not achieving treatment goals with their initial randomized therapy in the ongoing phase 3 SELECT-COMPARE study.</p><p><strong>Methods: </strong>Patients with non-response or incomplete response to initially prescribed upadacitinib 15 mg once daily or adalimumab 40 mg every other week were switched to the alternate therapy by week 26. Efficacy was evaluated through 228 weeks post-switch using validated outcome measures, including Clinical Disease Activity Index (CDAI) low disease activity (LDA; ≤ 10)/remission (≤ 2.8); 28-joint Disease Activity Score based on C-reactive protein ≤ 3.2/< 2.6; ≥ 20%/50%/70% improvement in American College of Rheumatology (ACR) response criteria; and change from baseline in ACR core components. Data are reported as observed. Safety was assessed by treatment-emergent adverse events (TEAEs) through week 264.</p><p><strong>Results: </strong>Of patients initially randomized to upadacitinib and adalimumab, 38.7% and 48.6%, respectively, switched to the alternate therapy by week 26. Clinically relevant improvements in all efficacy measures were observed through 228 weeks post-switch and were generally similar between groups, with small numeric differences mostly in favor of switching to upadacitinib. CDAI remission was achieved by 32.7% and 28.6% of initial non-responders, and 27.5% and 27.3% of incomplete responders, while CDAI LDA was achieved by 76.9% and 72.9% of non-responders, and 72.5% and 72.7% of incomplete responders switching to upadacitinib and to adalimumab, respectively. TEAE rates were similar between groups, although herpes zoster infection, lymphopenia, and creatine phosphokinase elevation were more frequent when switching to upadacitinib. No new safety signals were identified.</p><p><strong>Conclusion: </strong>Switching to a different MoA may provide long-term benefit to patients with RA not achieving treatment goals with their initial therapy, with acceptable safety profiles.</p><p><strong>Trial registration: </strong>NCT02629159.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-15DOI: 10.1007/s40744-024-00656-3
Xenofon Baraliakos, Annette E Szumski, Kenneth K Kwok, Bonnie Vlahos, Cecilia E Borlenghi
Introduction: Short-term placebo (PBO)- or active-controlled clinical studies have demonstrated that etanercept (ETN) is effective and well tolerated in patients with radiographic axial spondyloarthritis (r-axSpA) with long-term efficacy and safety continuing for up to 7 years after treatment start. Short-term randomized controlled trials (RCTs) have shown the efficacy of ETN after 12-24 weeks, with statistically significant improvements as early as week 2. This post hoc analysis investigated the timeframe (i.e., temporal responses) in which patients with r-axSpA achieved their first clinical response with ETN and how patients responded over a longer period according to different temporal responses in index studies.
Methods: Data were analyzed from three phase 3/4 PBO- or sulfasalazine-controlled RCTs of ETN for the treatment of r-axSpA (index studies). Long-term open-label extension (OLE) studies assessed how patients responded over a longer period according to different temporal responses ("Early," "Intermediate," "Late," or "Non-response") in their corresponding index studies.
Results: Within each index study, patient responses differed significantly between ETN and control arms for achievement of Assessment in SpondyloArthritis international Society (ASAS) 20 and other measures of treatment response. In general, the proportion of responders in the OLE studies was high for those with "Early" and "Intermediate" responses as defined in the index studies. Despite patients being considered non-responders in the index studies, a large proportion achieved response on continued treatment in the OLE studies over the longer term, including through 48 weeks.
Conclusions: Response in the index studies was maintained in the long term, and continued treatment was warranted in a large proportion of patients despite initial non-response. Absence of an early response in index studies did not predict non-response over the long term, and early response to treatment was not always a predictor for later response.
导言:短期安慰剂(PBO)或活性对照临床研究表明,依那西普(ETN)对放射性轴性脊柱关节炎(r-axSpA)患者有效且耐受性良好,其长期疗效和安全性可持续到治疗开始后的7年。短期随机对照试验(RCT)显示,ETN 在 12-24 周后具有疗效,最早在第 2 周就有了统计学意义上的显著改善。这项事后分析调查了r-axSpA患者首次获得ETN临床反应的时间范围(即时间反应),以及根据指数研究中不同的时间反应,患者如何在更长的时间内获得反应:对ETN治疗r-axSpA的三项3/4期PBO或磺胺嘧啶对照RCT(指标研究)的数据进行了分析。长期开放标签延伸(OLE)研究根据相应指标研究中的不同时间反应("早期"、"中期"、"晚期 "或 "无反应")评估了患者在更长时期内的反应情况:结果:在每项指标研究中,ETN治疗组和对照组患者在达到国际脊柱关节炎协会(ASAS)20评估指标和其他治疗反应指标方面存在显著差异。一般来说,在 OLE 研究中,指数研究中定义的 "早期 "和 "中期 "反应患者的比例较高。尽管在指标研究中,患者被认为是无应答者,但在 OLE 研究中,很大一部分患者在持续治疗 48 周等较长时间后获得了应答:结论:指数研究中的应答可长期维持,尽管最初无应答,但大部分患者仍有必要继续治疗。在指标研究中,早期无应答并不能预测长期无应答,而且早期治疗反应并不总是后期反应的预测因素:NCT00421915;NCT00247962;NCT00356356;NCT00421980;NCT00410046。
{"title":"Long-term Etanercept Response for Patients with Radiographic Axial Spondyloarthritis Based on Achievement of Early, Intermediate, or Late Responses During Index Studies.","authors":"Xenofon Baraliakos, Annette E Szumski, Kenneth K Kwok, Bonnie Vlahos, Cecilia E Borlenghi","doi":"10.1007/s40744-024-00656-3","DOIUrl":"10.1007/s40744-024-00656-3","url":null,"abstract":"<p><strong>Introduction: </strong>Short-term placebo (PBO)- or active-controlled clinical studies have demonstrated that etanercept (ETN) is effective and well tolerated in patients with radiographic axial spondyloarthritis (r-axSpA) with long-term efficacy and safety continuing for up to 7 years after treatment start. Short-term randomized controlled trials (RCTs) have shown the efficacy of ETN after 12-24 weeks, with statistically significant improvements as early as week 2. This post hoc analysis investigated the timeframe (i.e., temporal responses) in which patients with r-axSpA achieved their first clinical response with ETN and how patients responded over a longer period according to different temporal responses in index studies.</p><p><strong>Methods: </strong>Data were analyzed from three phase 3/4 PBO- or sulfasalazine-controlled RCTs of ETN for the treatment of r-axSpA (index studies). Long-term open-label extension (OLE) studies assessed how patients responded over a longer period according to different temporal responses (\"Early,\" \"Intermediate,\" \"Late,\" or \"Non-response\") in their corresponding index studies.</p><p><strong>Results: </strong>Within each index study, patient responses differed significantly between ETN and control arms for achievement of Assessment in SpondyloArthritis international Society (ASAS) 20 and other measures of treatment response. In general, the proportion of responders in the OLE studies was high for those with \"Early\" and \"Intermediate\" responses as defined in the index studies. Despite patients being considered non-responders in the index studies, a large proportion achieved response on continued treatment in the OLE studies over the longer term, including through 48 weeks.</p><p><strong>Conclusions: </strong>Response in the index studies was maintained in the long term, and continued treatment was warranted in a large proportion of patients despite initial non-response. Absence of an early response in index studies did not predict non-response over the long term, and early response to treatment was not always a predictor for later response.</p><p><strong>Trial registration: </strong>NCT00421915; NCT00247962; NCT00356356; NCT00421980; NCT00410046.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-06DOI: 10.1007/s40744-024-00655-4
Fabio Massimo Perrotta, Rossana Scrivo, Salvatore D'Angelo, Silvia Scriffignano, Andrea Delle Sedie, Laura Coates, Ennio Lubrano
Introduction: An overarching principle for the management of psoriatic arthritis (PsA) is a shared decision-making process between physicians and patients. The aim of this study is to assess the patient-physician relationship in a group of patients with PsA, by using the Perceived Efficacy in Patient-Physician Interactions (PEPPI) and CollaboRATE instruments.
Methods: This is a cross-sectional multicenter study where consecutive patients with PsA were enrolled. For each patient, the main demographic, comorbid conditions, and clinical data were collected, including the assessment of disease activity, function, quality of life, and impact of disease. PEPPI and CollaboRATE questionnaires were used, respectively, to evaluate the patient's perception of the patient-physician relationship and the shared decision-making process.
Results: A total of 81 patients with PsA were enrolled at four centers in Italy. Overall, our patients showed a high level of confidence in obtaining needed health care, with relatively high median (IQR) values of PEPPI (20; 16-23), and a good shared decision-making process, with high median (IQR) values of CollaboRATE questionnaire (7; 6-9). PEPPI and CollaboRATE scores showed a statistically significant inverse correlation with different clinical variables such as disease duration, Leeds Enthesitis Index, PsA impact of Disease, Health Assessment Questionnaire, pain, patient's global assessment of disease activity and clinical disease activity for PsA. The presence of comorbidities did not appear to be associated with lower values of PEPPI and CollaboRATE.
Conclusions: In this study, few patients with PsA were at risk of suboptimal communication with their physician. This phenomenon appeared to be primarily related to higher disease activity and burden.
{"title":"Assessment of Patient-Physician Interactions in Psoriatic Arthritis: National Results of the ASSIST Study.","authors":"Fabio Massimo Perrotta, Rossana Scrivo, Salvatore D'Angelo, Silvia Scriffignano, Andrea Delle Sedie, Laura Coates, Ennio Lubrano","doi":"10.1007/s40744-024-00655-4","DOIUrl":"10.1007/s40744-024-00655-4","url":null,"abstract":"<p><strong>Introduction: </strong>An overarching principle for the management of psoriatic arthritis (PsA) is a shared decision-making process between physicians and patients. The aim of this study is to assess the patient-physician relationship in a group of patients with PsA, by using the Perceived Efficacy in Patient-Physician Interactions (PEPPI) and CollaboRATE instruments.</p><p><strong>Methods: </strong>This is a cross-sectional multicenter study where consecutive patients with PsA were enrolled. For each patient, the main demographic, comorbid conditions, and clinical data were collected, including the assessment of disease activity, function, quality of life, and impact of disease. PEPPI and CollaboRATE questionnaires were used, respectively, to evaluate the patient's perception of the patient-physician relationship and the shared decision-making process.</p><p><strong>Results: </strong>A total of 81 patients with PsA were enrolled at four centers in Italy. Overall, our patients showed a high level of confidence in obtaining needed health care, with relatively high median (IQR) values of PEPPI (20; 16-23), and a good shared decision-making process, with high median (IQR) values of CollaboRATE questionnaire (7; 6-9). PEPPI and CollaboRATE scores showed a statistically significant inverse correlation with different clinical variables such as disease duration, Leeds Enthesitis Index, PsA impact of Disease, Health Assessment Questionnaire, pain, patient's global assessment of disease activity and clinical disease activity for PsA. The presence of comorbidities did not appear to be associated with lower values of PEPPI and CollaboRATE.</p><p><strong>Conclusions: </strong>In this study, few patients with PsA were at risk of suboptimal communication with their physician. This phenomenon appeared to be primarily related to higher disease activity and burden.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-03-06DOI: 10.1007/s40744-024-00652-7
Philip J Mease, Richard B Warren, Peter Nash, Jean-Marie Grouin, Nikos Lyris, Damon Willems, Vanessa Taieb, Jason Eells, Iain B McInnes
Introduction: Matching-adjusted indirect comparisons (MAICs) were used to compare the efficacy of bimekizumab and secukinumab 150 mg and 300 mg at 52 weeks for the treatment of psoriatic arthritis (PsA) in patients who were biologic disease-modifying anti-rheumatic drug-naïve (bDMARD-naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR).
Methods: Relevant trials were systematically identified. Individual patient data from bimekizumab randomized controlled trials, BE OPTIMAL (N = 431) and BE COMPLETE (N = 267), were matched to aggregate data from bDMARD-naïve and TNFi-IR patient subgroups from FUTURE 2 using secukinumab 150 mg and 300 mg doses (bDMARD-naïve: N = 63/37; TNFi-IR: N = 67/33). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of patients in the secukinumab trials. Unanchored comparisons of recalculated bimekizumab and secukinumab 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed.
Results: In patients who were bDMARD-naïve, bimekizumab had a greater likelihood of ACR70 response than secukinumab 150 mg (odds ratio [95% confidence interval] 2.39 [1.26, 4.53]; p = 0.008) and secukinumab 300 mg (2.03 [1.11, 3.72]; p = 0.021) at 52 weeks. In patients who were TNFi-IR, bimekizumab had a greater likelihood of response compared to secukinumab 150 mg for ACR20 (3.50 [1.64-7.49]; p = 0.001), ACR50 (3.32 [1.41, 7.80]; p = 0.006), ACR70 (2.95 [1.08, 8.07]; p = 0.035) and MDA (3.52 [1.38, 8.99]; p = 0.009), and a greater likelihood of response compared to secukinumab 300 mg for ACR50 (2.44 [1.06, 5.65]; p = 0.037) and MDA (2.92 [1.20, 7.09]; p = 0.018) at 52 weeks.
Conclusion: In this MAIC analysis, the efficacy of bimekizumab, as demonstrated by the likelihood of ACR20/50/70 and MDA response at 52 weeks, was greater or comparable to secukinumab 150 mg and 300 mg for patients with PsA who were bDMARD-naïve and TNFi-IR.
{"title":"Comparative Effectiveness of Bimekizumab and Secukinumab in Patients with Psoriatic Arthritis at 52 Weeks Using a Matching-Adjusted Indirect Comparison.","authors":"Philip J Mease, Richard B Warren, Peter Nash, Jean-Marie Grouin, Nikos Lyris, Damon Willems, Vanessa Taieb, Jason Eells, Iain B McInnes","doi":"10.1007/s40744-024-00652-7","DOIUrl":"10.1007/s40744-024-00652-7","url":null,"abstract":"<p><strong>Introduction: </strong>Matching-adjusted indirect comparisons (MAICs) were used to compare the efficacy of bimekizumab and secukinumab 150 mg and 300 mg at 52 weeks for the treatment of psoriatic arthritis (PsA) in patients who were biologic disease-modifying anti-rheumatic drug-naïve (bDMARD-naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR).</p><p><strong>Methods: </strong>Relevant trials were systematically identified. Individual patient data from bimekizumab randomized controlled trials, BE OPTIMAL (N = 431) and BE COMPLETE (N = 267), were matched to aggregate data from bDMARD-naïve and TNFi-IR patient subgroups from FUTURE 2 using secukinumab 150 mg and 300 mg doses (bDMARD-naïve: N = 63/37; TNFi-IR: N = 67/33). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of patients in the secukinumab trials. Unanchored comparisons of recalculated bimekizumab and secukinumab 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed.</p><p><strong>Results: </strong>In patients who were bDMARD-naïve, bimekizumab had a greater likelihood of ACR70 response than secukinumab 150 mg (odds ratio [95% confidence interval] 2.39 [1.26, 4.53]; p = 0.008) and secukinumab 300 mg (2.03 [1.11, 3.72]; p = 0.021) at 52 weeks. In patients who were TNFi-IR, bimekizumab had a greater likelihood of response compared to secukinumab 150 mg for ACR20 (3.50 [1.64-7.49]; p = 0.001), ACR50 (3.32 [1.41, 7.80]; p = 0.006), ACR70 (2.95 [1.08, 8.07]; p = 0.035) and MDA (3.52 [1.38, 8.99]; p = 0.009), and a greater likelihood of response compared to secukinumab 300 mg for ACR50 (2.44 [1.06, 5.65]; p = 0.037) and MDA (2.92 [1.20, 7.09]; p = 0.018) at 52 weeks.</p><p><strong>Conclusion: </strong>In this MAIC analysis, the efficacy of bimekizumab, as demonstrated by the likelihood of ACR20/50/70 and MDA response at 52 weeks, was greater or comparable to secukinumab 150 mg and 300 mg for patients with PsA who were bDMARD-naïve and TNFi-IR.</p><p><strong>Trial registration numbers: </strong>NCT03895203, NCT03896581, NCT04009499, NCT01752634, NCT01989468, NCT02294227, NCT02404350.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1007/s40744-024-00662-5
Lars Erik Kristensen, Atul Deodhar, Ying-Ying Leung, Ivana Vranic, Mahta Mortezavi, Lara Fallon, Arne Yndestad, Cassandra D. Kinch, Dafna D. Gladman
In this commentary, we review clinical data which helps inform individualized benefit–risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50 years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65 years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients < 65 years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65 years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.
{"title":"Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data","authors":"Lars Erik Kristensen, Atul Deodhar, Ying-Ying Leung, Ivana Vranic, Mahta Mortezavi, Lara Fallon, Arne Yndestad, Cassandra D. Kinch, Dafna D. Gladman","doi":"10.1007/s40744-024-00662-5","DOIUrl":"https://doi.org/10.1007/s40744-024-00662-5","url":null,"abstract":"<p>In this commentary, we review clinical data which helps inform individualized benefit–risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50 years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65 years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients < 65 years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65 years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.</p><p><b>Trial Registration:</b> NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364, NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-29DOI: 10.1007/s40744-024-00671-4
Gerd R. Burmester, Jayne Stigler, Andrea Rubbert-Roth, Yoshiya Tanaka, Valderilio F. Azevedo, Derek Coombs, Ivan Lagunes, Ralph Lippe, Peter Wung, Lianne S. Gensler
Introduction
This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]).
Methods
Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY).
Results
A total of 1789 patients (PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (n = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases.
Conclusion
Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified.
{"title":"Safety Profile of Upadacitinib up to 5 Years in Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis: An Integrated Analysis of Clinical Trials","authors":"Gerd R. Burmester, Jayne Stigler, Andrea Rubbert-Roth, Yoshiya Tanaka, Valderilio F. Azevedo, Derek Coombs, Ivan Lagunes, Ralph Lippe, Peter Wung, Lianne S. Gensler","doi":"10.1007/s40744-024-00671-4","DOIUrl":"https://doi.org/10.1007/s40744-024-00671-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 1789 patients (PsA, <i>n</i> = 907; AS, <i>n</i> = 596; nr-axSpA, <i>n</i> = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (<i>n</i> = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration</h3><p>SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-25DOI: 10.1007/s40744-024-00663-4
Andri Phoka, B. J. F. van den Bemt, E. Lubrano, Inderjit Singh, C. Fernández-Carballido, Detlev Parow, D. Webb, Fabienne Lacombe, Laura Harrington, X. Baraliakos
{"title":"Elevating the Standard of Care for Patients with Axial Spondyloarthritis: 'Calls to Action' from Rheumacensus, a Multistakeholder Pan-European Initiative.","authors":"Andri Phoka, B. J. F. van den Bemt, E. Lubrano, Inderjit Singh, C. Fernández-Carballido, Detlev Parow, D. Webb, Fabienne Lacombe, Laura Harrington, X. Baraliakos","doi":"10.1007/s40744-024-00663-4","DOIUrl":"https://doi.org/10.1007/s40744-024-00663-4","url":null,"abstract":"","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}