Modulation of interleukin-23 signaling with guselkumab in biologic-naive patients versus tumor necrosis factor inhibitor–inadequate responders with active psoriatic arthritis
<p><b>Objective</b></p> We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)–23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic-naive or had inadequ...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2024
|
| _version_ | 1826313449046540288 |
|---|---|
| author | Siebert, S Coates, LC Schett, G Raychaudhuri, SP Chen, W Gao, S Seridi, L Chakravarty, SD Shawi, M Lavie, F Sharaf, M Zimmermann, M Kollmeier, AP Xu, XL Rahman, P Mease, PJ Deodhar, A |
| author_facet | Siebert, S Coates, LC Schett, G Raychaudhuri, SP Chen, W Gao, S Seridi, L Chakravarty, SD Shawi, M Lavie, F Sharaf, M Zimmermann, M Kollmeier, AP Xu, XL Rahman, P Mease, PJ Deodhar, A |
| author_sort | Siebert, S |
| collection | OXFORD |
| description | <p><b>Objective</b></p>
We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)–23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic-naive or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR).
<p><b>Methods</b></p>
Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8 weeks were compared between biologic-naive (n = 251) and TNFi-IR (n = 93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups.
<p><b>Results</b></p>
Baseline IL-22, TNFα, and beta defensin-2 (BD-2) levels were significantly lower in biologic-naive than in TNFi-IR participants. With guselkumab, week 24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naive and TNFi-IR participants (≥1.4-fold difference, nominal P < 0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL-17A, IL-17F, BD-2 in biologic-naive PASI 90 responders; IL-17A, BD-2 in TNFi-IR IGA 0/1 responders; IL-22, BD-2 in TNFi-IR PASI 90 responders [nominal P < 0.05]) and trended higher in TNFi-IR ACR20 responders.
<p><b>Conclusion</b></p>
Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naive and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses to guselkumab suggest greater dysregulation of IL-23/Th17 signaling in patients with TNFi-IR. |
| first_indexed | 2024-03-07T08:18:15Z |
| format | Journal article |
| id | oxford-uuid:23c68185-51c8-483a-9aca-b5d8f3e83668 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:13:25Z |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:23c68185-51c8-483a-9aca-b5d8f3e836682024-07-15T10:43:12ZModulation of interleukin-23 signaling with guselkumab in biologic-naive patients versus tumor necrosis factor inhibitor–inadequate responders with active psoriatic arthritisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:23c68185-51c8-483a-9aca-b5d8f3e83668EnglishSymplectic ElementsWiley2024Siebert, SCoates, LCSchett, GRaychaudhuri, SPChen, WGao, SSeridi, LChakravarty, SDShawi, MLavie, FSharaf, MZimmermann, MKollmeier, APXu, XLRahman, PMease, PJDeodhar, A<p><b>Objective</b></p> We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)–23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic-naive or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR). <p><b>Methods</b></p> Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8 weeks were compared between biologic-naive (n = 251) and TNFi-IR (n = 93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups. <p><b>Results</b></p> Baseline IL-22, TNFα, and beta defensin-2 (BD-2) levels were significantly lower in biologic-naive than in TNFi-IR participants. With guselkumab, week 24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naive and TNFi-IR participants (≥1.4-fold difference, nominal P < 0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL-17A, IL-17F, BD-2 in biologic-naive PASI 90 responders; IL-17A, BD-2 in TNFi-IR IGA 0/1 responders; IL-22, BD-2 in TNFi-IR PASI 90 responders [nominal P < 0.05]) and trended higher in TNFi-IR ACR20 responders. <p><b>Conclusion</b></p> Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naive and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses to guselkumab suggest greater dysregulation of IL-23/Th17 signaling in patients with TNFi-IR. |
| spellingShingle | Siebert, S Coates, LC Schett, G Raychaudhuri, SP Chen, W Gao, S Seridi, L Chakravarty, SD Shawi, M Lavie, F Sharaf, M Zimmermann, M Kollmeier, AP Xu, XL Rahman, P Mease, PJ Deodhar, A Modulation of interleukin-23 signaling with guselkumab in biologic-naive patients versus tumor necrosis factor inhibitor–inadequate responders with active psoriatic arthritis |
| title | Modulation of interleukin-23 signaling with guselkumab in biologic-naive patients versus tumor necrosis factor inhibitor–inadequate responders with active psoriatic arthritis |
| title_full | Modulation of interleukin-23 signaling with guselkumab in biologic-naive patients versus tumor necrosis factor inhibitor–inadequate responders with active psoriatic arthritis |
| title_fullStr | Modulation of interleukin-23 signaling with guselkumab in biologic-naive patients versus tumor necrosis factor inhibitor–inadequate responders with active psoriatic arthritis |
| title_full_unstemmed | Modulation of interleukin-23 signaling with guselkumab in biologic-naive patients versus tumor necrosis factor inhibitor–inadequate responders with active psoriatic arthritis |
| title_short | Modulation of interleukin-23 signaling with guselkumab in biologic-naive patients versus tumor necrosis factor inhibitor–inadequate responders with active psoriatic arthritis |
| title_sort | modulation of interleukin 23 signaling with guselkumab in biologic naive patients versus tumor necrosis factor inhibitor inadequate responders with active psoriatic arthritis |
| work_keys_str_mv | AT sieberts modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT coateslc modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT schettg modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT raychaudhurisp modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT chenw modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT gaos modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT seridil modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT chakravartysd modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT shawim modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT lavief modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT sharafm modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT zimmermannm modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT kollmeierap modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT xuxl modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT rahmanp modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT measepj modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis AT deodhara modulationofinterleukin23signalingwithguselkumabinbiologicnaivepatientsversustumornecrosisfactorinhibitorinadequateresponderswithactivepsoriaticarthritis |