Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS)
<p><strong>Objective</strong> To evaluate efficacy and safety of guselkumab, an anti-interleukin-23p19-subunit antibody, in patients with psoriatic arthritis (PsA) with prior inadequate response (IR) to tumour necrosis factor inhibitors (TNFi).</p> <p><strong>Met...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
BMJ Publishing Group
2021
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| _version_ | 1826299194173816832 |
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| author | Coates, L Gossec, L Theander, E Bergmans, P Neuhold, M Karyekar, CS Shawi, M Noel, W Schett, G McInnes, IB |
| author_facet | Coates, L Gossec, L Theander, E Bergmans, P Neuhold, M Karyekar, CS Shawi, M Noel, W Schett, G McInnes, IB |
| author_sort | Coates, L |
| collection | OXFORD |
| description | <p><strong>Objective</strong> To evaluate efficacy and safety of guselkumab, an anti-interleukin-23p19-subunit antibody, in patients with psoriatic arthritis (PsA) with prior inadequate response (IR) to tumour necrosis factor inhibitors (TNFi).</p>
<p><strong>Methods</strong> Adults with active PsA (≥3 swollen and ≥3 tender joints) who discontinued ≤2 TNFi due to IR (lack of efficacy or intolerance) were randomised (2:1) to subcutaneous guselkumab 100 mg or placebo at week 0, week 4, then every 8 weeks (Q8W) through week 44. Patients receiving placebo crossed over to guselkumab at week 24. The primary (ACR20) and key secondary (change in HAQ-DI, ACR50, change in SF-36 PCS and PASI100) endpoints, at week 24, underwent fixed-sequence testing (two-sided α=0.05). Adverse events (AEs) were assessed through week 56.</p>
<p><strong>Results</strong> Among 285 participants (female (52%), one (88%) or two (12%) prior TNFi), 88% of 189 guselkumab and 86% of 96 placebo→guselkumab patients completed study agent through week 44. A statistically significantly higher proportion of patients receiving guselkumab (44.4%) than placebo (19.8%) achieved ACR20 (%difference (95% CI): 24.6 (14.1 to 35.2); multiplicity-adjusted p<0.001) at week 24. Guselkumab was superior to placebo for each key secondary endpoint (multiplicity-adjusted p<0.01). ACR20 response (non-responder imputation) in the guselkumab group was 58% at week 48; >80% of week 24 responders maintained response at week 48. Through week 24, serious AEs/serious infections occurred in 3.7%/0.5% of 189 guselkumab-randomised and 3.1%/0% of 96 placebo-randomised patients; the guselkumab safety profile was similar through week 56, with no deaths or opportunistic infections.</p>
<p><strong>Conclusion</strong> Guselkumab significantly improved joint and skin manifestations and physical function in patients with TNFi-IR PsA. A favourable benefit–risk profile was demonstrated through 1 year.</p>
<p><strong>Trial registration number</strong> NCT03796858.</p> |
| first_indexed | 2024-03-07T04:58:11Z |
| format | Journal article |
| id | oxford-uuid:d758e343-3219-42d3-9792-51afb13d07a7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:58:11Z |
| publishDate | 2021 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:d758e343-3219-42d3-9792-51afb13d07a72022-03-27T08:40:32ZEfficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS)Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d758e343-3219-42d3-9792-51afb13d07a7EnglishSymplectic ElementsBMJ Publishing Group2021Coates, LGossec, LTheander, EBergmans, PNeuhold, MKaryekar, CSShawi, MNoel, WSchett, GMcInnes, IB<p><strong>Objective</strong> To evaluate efficacy and safety of guselkumab, an anti-interleukin-23p19-subunit antibody, in patients with psoriatic arthritis (PsA) with prior inadequate response (IR) to tumour necrosis factor inhibitors (TNFi).</p> <p><strong>Methods</strong> Adults with active PsA (≥3 swollen and ≥3 tender joints) who discontinued ≤2 TNFi due to IR (lack of efficacy or intolerance) were randomised (2:1) to subcutaneous guselkumab 100 mg or placebo at week 0, week 4, then every 8 weeks (Q8W) through week 44. Patients receiving placebo crossed over to guselkumab at week 24. The primary (ACR20) and key secondary (change in HAQ-DI, ACR50, change in SF-36 PCS and PASI100) endpoints, at week 24, underwent fixed-sequence testing (two-sided α=0.05). Adverse events (AEs) were assessed through week 56.</p> <p><strong>Results</strong> Among 285 participants (female (52%), one (88%) or two (12%) prior TNFi), 88% of 189 guselkumab and 86% of 96 placebo→guselkumab patients completed study agent through week 44. A statistically significantly higher proportion of patients receiving guselkumab (44.4%) than placebo (19.8%) achieved ACR20 (%difference (95% CI): 24.6 (14.1 to 35.2); multiplicity-adjusted p<0.001) at week 24. Guselkumab was superior to placebo for each key secondary endpoint (multiplicity-adjusted p<0.01). ACR20 response (non-responder imputation) in the guselkumab group was 58% at week 48; >80% of week 24 responders maintained response at week 48. Through week 24, serious AEs/serious infections occurred in 3.7%/0.5% of 189 guselkumab-randomised and 3.1%/0% of 96 placebo-randomised patients; the guselkumab safety profile was similar through week 56, with no deaths or opportunistic infections.</p> <p><strong>Conclusion</strong> Guselkumab significantly improved joint and skin manifestations and physical function in patients with TNFi-IR PsA. A favourable benefit–risk profile was demonstrated through 1 year.</p> <p><strong>Trial registration number</strong> NCT03796858.</p> |
| spellingShingle | Coates, L Gossec, L Theander, E Bergmans, P Neuhold, M Karyekar, CS Shawi, M Noel, W Schett, G McInnes, IB Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS) |
| title | Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS) |
| title_full | Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS) |
| title_fullStr | Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS) |
| title_full_unstemmed | Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS) |
| title_short | Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS) |
| title_sort | efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors results through one year of a phase iiib randomised controlled study cosmos |
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