Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study
Abstract Background To explore the trajectory of, and factors contributing to, achievement of individual criteria of minimal disease activity (MDA) in patients with active psoriatic arthritis (PsA) treated with guselkumab. Methods The Phase 3, randomized, placebo-controlled DISCOVER-2 study enrolled...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Rheumatology |
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| Online Access: | https://doi.org/10.1186/s41927-024-00375-w |
| _version_ | 1797272803353821184 |
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| author | Laura C. Coates Proton Rahman Philip J. Mease May Shawi Emmanouil Rampakakis Alexa P. Kollmeier Xie L. Xu Soumya D. Chakravarty Iain B. McInnes Lai-Shan Tam |
| author_facet | Laura C. Coates Proton Rahman Philip J. Mease May Shawi Emmanouil Rampakakis Alexa P. Kollmeier Xie L. Xu Soumya D. Chakravarty Iain B. McInnes Lai-Shan Tam |
| author_sort | Laura C. Coates |
| collection | DOAJ |
| description | Abstract Background To explore the trajectory of, and factors contributing to, achievement of individual criteria of minimal disease activity (MDA) in patients with active psoriatic arthritis (PsA) treated with guselkumab. Methods The Phase 3, randomized, placebo-controlled DISCOVER-2 study enrolled adults (N = 739) with active PsA despite standard therapies who were biologic/Janus kinase inhibitor-naive. Patients were randomized 1:1:1 to guselkumab 100 mg every 4 weeks; guselkumab 100 mg at week 0, week 4, then every 8 weeks; or placebo. In this post hoc analysis, patients randomized to guselkumab were included and pooled (N = 493). Longitudinal trajectories of achieving each MDA criterion through week 100 were derived using non-responder imputation. Time to achieve each criterion was estimated with Kaplan-Meier analysis. Multivariate regression for time to achieve each criterion (Cox regression) and achievement at week 100 (logistic regression) was used to identify contributing factors. Results Continuous improvement across all MDA domains was shown over time. ~70% of patients achieved near remission in swollen joint count (SJC), Psoriasis Area and Severity Index (PASI), and enthesitis through week 100. Median times to achieve individual criteria differed significantly (p < 0.0001), with SJC ≤ 1 (20 weeks), PASI ≤ 1 (16 weeks), and ≤ 1 tender entheses (16 weeks) being faster than patient-reported criteria (pain ≤ 15 mm, patient global assessment of arthritis and psoriasis ≤ 20 mm, Health Assessment Questionnaire-Disability Index ≤ 0.5) and tender joint count ≤ 1. Higher baseline domain scores, older age, worse fatigue, and increased body mass index were significant predictors of longer time to achieve minimal levels of disease activity assessed via patient-reported criteria. Conclusions Substantial proportions of guselkumab-treated patients achieved individual MDA criteria, each showing continuous improvement through week 100, although with distinct trajectories. Median times to achieve physician-assessed MDA criteria were significantly faster compared with patient-driven criteria. Identification of modifiable factors affecting the time to achieve patient-reported criteria has the potential to optimize the achievement and sustainability of MDA in the clinic via a multidisciplinary approach to managing PsA, involving both medical and lifestyle interventions. Trial registration number NCT03158285. Trial registration date May 16, 2017. |
| first_indexed | 2024-03-07T14:34:59Z |
| format | Article |
| id | doaj.art-194d9d5826a142a58b96c1820ee7de94 |
| institution | Directory Open Access Journal |
| issn | 2520-1026 |
| language | English |
| last_indexed | 2024-03-07T14:34:59Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Rheumatology |
| spelling | doaj.art-194d9d5826a142a58b96c1820ee7de942024-03-05T20:41:16ZengBMCBMC Rheumatology2520-10262024-02-018111110.1186/s41927-024-00375-wContinuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled studyLaura C. Coates0Proton Rahman1Philip J. Mease2May Shawi3Emmanouil Rampakakis4Alexa P. Kollmeier5Xie L. Xu6Soumya D. Chakravarty7Iain B. McInnes8Lai-Shan Tam9Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of OxfordCraig L Dobbin Genetics Research Centre, St. John’s, Newfoundland and Labrador, Memorial University of NewfoundlandDepartment of Rheumatology Research, Swedish Medical Center/Providence St Joseph Health, University of WashingtonJanssen Research & Development, LLCDepartment of Pediatrics, McGill UniversityJanssen Research & Development, LLC. ImmunologyJanssen Research & Development, LLC. ImmunologyJanssen Scientific Affairs, LLCCollege of Medical Veterinary and Life Sciences, University of GlasgowDepartment of Medicine & Therapeutics, The Chinese University of Hong KongAbstract Background To explore the trajectory of, and factors contributing to, achievement of individual criteria of minimal disease activity (MDA) in patients with active psoriatic arthritis (PsA) treated with guselkumab. Methods The Phase 3, randomized, placebo-controlled DISCOVER-2 study enrolled adults (N = 739) with active PsA despite standard therapies who were biologic/Janus kinase inhibitor-naive. Patients were randomized 1:1:1 to guselkumab 100 mg every 4 weeks; guselkumab 100 mg at week 0, week 4, then every 8 weeks; or placebo. In this post hoc analysis, patients randomized to guselkumab were included and pooled (N = 493). Longitudinal trajectories of achieving each MDA criterion through week 100 were derived using non-responder imputation. Time to achieve each criterion was estimated with Kaplan-Meier analysis. Multivariate regression for time to achieve each criterion (Cox regression) and achievement at week 100 (logistic regression) was used to identify contributing factors. Results Continuous improvement across all MDA domains was shown over time. ~70% of patients achieved near remission in swollen joint count (SJC), Psoriasis Area and Severity Index (PASI), and enthesitis through week 100. Median times to achieve individual criteria differed significantly (p < 0.0001), with SJC ≤ 1 (20 weeks), PASI ≤ 1 (16 weeks), and ≤ 1 tender entheses (16 weeks) being faster than patient-reported criteria (pain ≤ 15 mm, patient global assessment of arthritis and psoriasis ≤ 20 mm, Health Assessment Questionnaire-Disability Index ≤ 0.5) and tender joint count ≤ 1. Higher baseline domain scores, older age, worse fatigue, and increased body mass index were significant predictors of longer time to achieve minimal levels of disease activity assessed via patient-reported criteria. Conclusions Substantial proportions of guselkumab-treated patients achieved individual MDA criteria, each showing continuous improvement through week 100, although with distinct trajectories. Median times to achieve physician-assessed MDA criteria were significantly faster compared with patient-driven criteria. Identification of modifiable factors affecting the time to achieve patient-reported criteria has the potential to optimize the achievement and sustainability of MDA in the clinic via a multidisciplinary approach to managing PsA, involving both medical and lifestyle interventions. Trial registration number NCT03158285. Trial registration date May 16, 2017.https://doi.org/10.1186/s41927-024-00375-wPsoriatic arthritisBiologicsGuselkumabMinimal disease activity |
| spellingShingle | Laura C. Coates Proton Rahman Philip J. Mease May Shawi Emmanouil Rampakakis Alexa P. Kollmeier Xie L. Xu Soumya D. Chakravarty Iain B. McInnes Lai-Shan Tam Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study BMC Rheumatology Psoriatic arthritis Biologics Guselkumab Minimal disease activity |
| title | Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study |
| title_full | Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study |
| title_fullStr | Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study |
| title_full_unstemmed | Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study |
| title_short | Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study |
| title_sort | continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis post hoc analysis of a phase 3 randomized double blind placebo controlled study |
| topic | Psoriatic arthritis Biologics Guselkumab Minimal disease activity |
| url | https://doi.org/10.1186/s41927-024-00375-w |
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