Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study
Abstract Introduction Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]), in post hoc analyse...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2023-10-01
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| Series: | Rheumatology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40744-023-00592-8 |
| _version_ | 1827708388522328064 |
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| author | Philip J. Mease Dafna D. Gladman Denis Poddubnyy Soumya D. Chakravarty May Shawi Alexa P. Kollmeier Xie L. Xu Stephen Xu Atul Deodhar Xenofon Baraliakos |
| author_facet | Philip J. Mease Dafna D. Gladman Denis Poddubnyy Soumya D. Chakravarty May Shawi Alexa P. Kollmeier Xie L. Xu Stephen Xu Atul Deodhar Xenofon Baraliakos |
| author_sort | Philip J. Mease |
| collection | DOAJ |
| description | Abstract Introduction Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]), in post hoc analyses of the phase 3, placebo-controlled, randomized DISCOVER-1 and DISCOVER-2 studies. We now evaluate durability of response in axial-related outcomes through 2 years of DISCOVER-2. Methods DISCOVER-2 biologic-naive adults with active PsA (≥ 5 tender/ ≥ 5 swollen joints, C-reactive protein ≥ 0.6 mg/dl) were randomized to guselkumab 100 mg every 4 weeks (Q4W) or at week 0, week 4, then Q8W, or placebo → guselkumab Q4W at week 24. Among patients with imaging-confirmed sacroiliitis (investigator-identified), axial symptoms were assessed through 2 years utilizing BASDAI, BASDAI Question #2 (spinal pain), modified BASDAI (mBASDAI; excludes Question #3 [peripheral joint pain]), and ASDAS. Mean changes in scores and proportions of patients achieving ≥ 50% improvement in BASDAI (BASDAI 50) and ASDAS responses, including major improvement (decrease ≥ 2.0), were determined through week 100. Treatment failure rules (through week 24) and nonresponder imputation of missing data (post-week 24) were utilized. Mean BASDAI component scores were assessed through week 100 (observed data). Exploratory analyses evaluated efficacy by sex and HLA-B*27 status. Results Among 246 patients with PsA and imaging-confirmed sacroiliitis, guselkumab-treated patients had greater mean improvements in BASDAI, mBASDAI, spinal pain, and ASDAS scores, lower mean BASDAI component scores, and greater response rates in achieving BASDAI 50 and ASDAS major improvement vs. placebo at week 24. Differences from placebo were observed for guselkumab-treated patients in selected endpoints regardless of sex or HLA-B*27 status. At week 100, mean improvements were ~ 3 points for all BASDAI scores and 1.6–1.7 for ASDAS; 49–54% achieved BASDAI 50 and 39% achieved ASDAS major improvement at week 100. Conclusions Guselkumab treatment provided durable and meaningful improvements in axial symptoms and disease activity in substantial proportions of patients with active PsA and imaging-confirmed sacroiliitis. Trial Registration Clinicaltrials.gov NCT03158285. |
| first_indexed | 2024-03-10T17:02:53Z |
| format | Article |
| id | doaj.art-78e3cd32eadf45c68aebb23a5cc1f2fa |
| institution | Directory Open Access Journal |
| issn | 2198-6576 2198-6584 |
| language | English |
| last_indexed | 2024-03-10T17:02:53Z |
| publishDate | 2023-10-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Rheumatology and Therapy |
| spelling | doaj.art-78e3cd32eadf45c68aebb23a5cc1f2fa2023-11-20T10:53:30ZengAdis, Springer HealthcareRheumatology and Therapy2198-65762198-65842023-10-011061637165310.1007/s40744-023-00592-8Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 StudyPhilip J. Mease0Dafna D. Gladman1Denis Poddubnyy2Soumya D. Chakravarty3May Shawi4Alexa P. Kollmeier5Xie L. Xu6Stephen Xu7Atul Deodhar8Xenofon Baraliakos9Department of Rheumatology, Swedish Medical Center/Providence St. Joseph Health and University of Washington, Rheumatology ResearchCentre for Prognosis Studies in the Rheumatic Diseases, Toronto Western HospitalCharité-Universitatsmedizin BerlinJanssen Scientific Affairs, LLCJanssen Research & Development, LLCJanssen Research & Development, LLCJanssen Research & Development, LLCJanssen Research & Development, LLCOregon Health & Science UniversityRheumazentrum Ruhrgebiet, Ruhr-University BochumAbstract Introduction Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]), in post hoc analyses of the phase 3, placebo-controlled, randomized DISCOVER-1 and DISCOVER-2 studies. We now evaluate durability of response in axial-related outcomes through 2 years of DISCOVER-2. Methods DISCOVER-2 biologic-naive adults with active PsA (≥ 5 tender/ ≥ 5 swollen joints, C-reactive protein ≥ 0.6 mg/dl) were randomized to guselkumab 100 mg every 4 weeks (Q4W) or at week 0, week 4, then Q8W, or placebo → guselkumab Q4W at week 24. Among patients with imaging-confirmed sacroiliitis (investigator-identified), axial symptoms were assessed through 2 years utilizing BASDAI, BASDAI Question #2 (spinal pain), modified BASDAI (mBASDAI; excludes Question #3 [peripheral joint pain]), and ASDAS. Mean changes in scores and proportions of patients achieving ≥ 50% improvement in BASDAI (BASDAI 50) and ASDAS responses, including major improvement (decrease ≥ 2.0), were determined through week 100. Treatment failure rules (through week 24) and nonresponder imputation of missing data (post-week 24) were utilized. Mean BASDAI component scores were assessed through week 100 (observed data). Exploratory analyses evaluated efficacy by sex and HLA-B*27 status. Results Among 246 patients with PsA and imaging-confirmed sacroiliitis, guselkumab-treated patients had greater mean improvements in BASDAI, mBASDAI, spinal pain, and ASDAS scores, lower mean BASDAI component scores, and greater response rates in achieving BASDAI 50 and ASDAS major improvement vs. placebo at week 24. Differences from placebo were observed for guselkumab-treated patients in selected endpoints regardless of sex or HLA-B*27 status. At week 100, mean improvements were ~ 3 points for all BASDAI scores and 1.6–1.7 for ASDAS; 49–54% achieved BASDAI 50 and 39% achieved ASDAS major improvement at week 100. Conclusions Guselkumab treatment provided durable and meaningful improvements in axial symptoms and disease activity in substantial proportions of patients with active PsA and imaging-confirmed sacroiliitis. Trial Registration Clinicaltrials.gov NCT03158285.https://doi.org/10.1007/s40744-023-00592-8Psoriatic arthritisAxialBiologicsGuselkumab |
| spellingShingle | Philip J. Mease Dafna D. Gladman Denis Poddubnyy Soumya D. Chakravarty May Shawi Alexa P. Kollmeier Xie L. Xu Stephen Xu Atul Deodhar Xenofon Baraliakos Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study Rheumatology and Therapy Psoriatic arthritis Axial Biologics Guselkumab |
| title | Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study |
| title_full | Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study |
| title_fullStr | Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study |
| title_full_unstemmed | Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study |
| title_short | Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study |
| title_sort | efficacy of guselkumab on axial related symptoms through up to 2 years in adults with active psoriatic arthritis in the phase 3 randomized placebo controlled discover 2 study |
| topic | Psoriatic arthritis Axial Biologics Guselkumab |
| url | https://doi.org/10.1007/s40744-023-00592-8 |
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