scholarly journals POS1036 COLLAGEN TURNOVER MARKERS ARE ASSOCIATED WITH ACTIVE PSORIATIC ARTHRITIS AND DECREASE WITH GUSELKUMAB TREATMENT IN A PHASE-3 CLINICAL TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 790.2-792
Author(s):  
G. Schett ◽  
M. J. Loza ◽  
A. Palanichamy ◽  
O. Fitzgerald ◽  
C. T. Ritchlin ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Structural Damage ◽  
Signs And Symptoms ◽  
Joint Disease ◽  
Type I ◽  
Healthy Controls ◽  
Phase 3 ◽  
Two Phase ◽  
Radiographic Damage ◽  
Collagen Formation

Background:Guselkumab (GUS), an interleukin-23p19-subunit monoclonal antibody, demonstrated efficacy compared to placebo (PBO) in reducing skin and musculoskeletal signs and symptoms in patients with active psoriatic arthritis (PsA) in two phase-3 studies, DISCOVER-1 & -2, and in retarding structural damage in DISCOVER-2.1,2Objectives:To evaluate tissue-derived extracellular matrix (ECM) products3,4 in serum of PsA patients in the DISCOVER-2 study and their relationship with radiographic damage, clinical response, and impact of treatment.Methods:In DISCOVER-2, patients were treated with GUS 100 mg at Week (w) 0, 4, then every 8w (q8w); GUS 100 mg every 4w (q4w); or matching PBO. At w24, PBO patients were crossed over to GUS q4w. A total of 11 serum biomarkers of ECM collagen formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4, and PRO-C6) and degradation (C1M, C2M, C3M, C4M, C6M, and COL10) were measured (by Nordic Bioscience) in a subset of 260 patients from the DISCOVER-2 program at Weeks 0, 4, 24, & 52 and in 76 healthy controls matched for age, sex, and ethnicity. PsA patients were selected randomly, though enriching for subjects with greatest radiographic changes, at Weeks 24 and 52. Significance defined by p<0.05 and |fold difference| ≥1.25.Results:At baseline, collagen degradation markers C1M, C3M, C4M, C6M and collagen formation markers PRO-C3 and PRO-C6 were significantly higher in the serum of PsA patients compared to matched healthy controls. Baseline C3M, C4M, and C6M were positively correlated to baseline skin and joint disease; baseline C1M, C3M, C4M, C6M, and PRO-C1 were positively correlated to baseline radiographic damage (data not shown). Levels of C1M (a maker indicating breakdown of collagen type I, the major collagen subtype in the bone) were significantly decreased after 24w treatment with GUS (Figure 1), reaching significant differences from placebo with the GUS 100 mg q4w group. For the PBO patients who crossed over to GUS at w24, there was also a reduction in this marker observed at w52 (Figure 1). In patients treated with GUS or PBO, there were no significant differences in baseline expression levels of the analytes in responders (patients achieving ACR20 at w24) compared with non-responders. However, ACR20 responders in the combined GUS group had a significantly greater reduction in C1M levels compared to non-responders (p=0.0065) at w24.Conclusion:This work provides evidence that collagen biomarkers in serum are dysregulated in patients with PsA compared to healthy controls, and that GUS impacts levels of these proteins. Importantly, C1M serves as a biomarker that tracks with joint response. We observed a greater reduction in C1M in ACR responders compared to non-responders, providing insight into how GUS may be working to protect from degradation of bone in PsA.References:[1]Deodhar A et al. Lancet 2020;395:1115-1125[2]Mease PJ et al. Lancet 2020;395:1126-1136[3]Gudmann NS et al. Clin Exp Rheumatol 2017;35:653-659[4]Sardar S et al. Annals of the Rheum Dis 2019;78(Suppl 2): https://ard.bmj.com/content/78/Suppl_2/867.1Disclosure of Interests:Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Roche, UCB, Consultant of: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Roche, UCB, Matthew J Loza Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Arumugam Palanichamy Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Oliver FitzGerald Speakers bureau: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Consultant of: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Christopher T. Ritchlin Speakers bureau: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Frederic Baribaud Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Kristen Sweet Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC.

scholarly journals OP0229 GUSELKUMAB INDUCES SUSTAINED REDUCTION IN ACUTE PHASE PROTEINS AND TH17 EFFECTOR CYTOKINES IN ACTIVE PSORIATIC ARTHRITIS IN TWO PHASE-3 CLINICAL TRIALS (DISCOVER-1 AND DISCOVER-2)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 144-145
Author(s):  
S. Siebert ◽  
I. Mcinnes ◽  
M. J. Loza ◽  
K. MA ◽  
K. Leander ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Proteins ◽  
Geometric Mean ◽  
Tnf Inhibitor ◽  
Healthy Controls ◽  
Phase 3 ◽  
Two Phase ◽  
Protein Levels ◽  
Disease Characteristics ◽  
Effector Cytokines

Background:Guselkumab (GUS), an IL-23 inhibitor monoclonal antibody (Mab) that specifically binds to the IL-23p19 subunit, demonstrated efficacy compared to placebo (PBO) in reducing skin and musculoskeletal signs and symptoms in patients (pts) with active psoriatic arthritis (PsA) in two phase-3 studies, DISCOVER 1 & 2.1,2Previous results from a GUS PsA Phase-2 trial3and Ustekinumab (UST, anti-IL12/23p40 MAb) PsA Phase-3 trials (PSUMMIT 1 & 2)4showed associations of baseline IL-17A, IL-17F, and CRP with baseline disease characteristics, and associations of GUS-induced cytokine reductions with clinical responses.Objectives:To investigate plausible cytokine expression in PsA and alterations after exposure to GUS therapy.Methods:In DISCOVER 1 & 2, pts were treated with GUS 100 mg at Wk 0, 4, then every 8Wks (q8w); GUS 100mg q4w; or matching PBO. 21 serum biomarkers were measured in a random subset of 300 PsA pts from the DISCOVER program at Weeks (Wks) 0, 4, & 24 and in 34 healthy controls matched for age, sex, and ethnicity. Serum proteins measured were acute phase reactants CRP & SAA (Meso Scale Discovery (MSD) Platform) and inflammatory cytokines/chemokines: Th17 effector cytokines IL-17A, IL-17F, & IL-22 (Single Molecule Counting Erenna® Immunoassay Platform) and soluble ICAM-1, soluble VCAM-1, IL-6, CXCL-8, IL-10, IL-13, IL-12p70, CCL22, IFN-γ, CCL2, CCL4, TNFα, IL-1β, IL-2, IL-4 (MSD), & YKL-40 (Quantikine Immunoassay). Serum IL-17A, IL-17B, & CRP measured in the Phase-3 PSUMMIT trials of UST for PsA4were included for comparison with GUS.Results:At baseline, serum levels of acute phase proteins CRP, SAA, & IL-6, and Th17-effector cytokines IL-17A & IL-17F were elevated in pts with PsA compared with healthy controls (p<0.05, geometric mean ≥ 40% higher, FIG 1). There was no significant dysregulation in the other cytokines measured in PsA pts compared to healthy controls. Baseline IL-17A, IL-17F, IL-22, & CCL22 were significantly associated with baseline psoriasis disease activity (Body Surface Area & Psoriatic Area and Severity Index, Spearman Signed Rank p<0.05, r>0.25). Baseline CRP, SAA, IL-6, & YKL40 were significantly associated with baseline joint disease (Disease Activity Score 28-CRP, Spearman p<0.05, r>0.25). Baseline SAA, IL-6, IL-17A, & IL-17F were higher in pts with prior TNF inhibitor exposure than without (p<0.05, geometric mean ≥ 40% higher), although pts with PsA both with and without prior TNF inhibitor had higher levels than the healthy control set.GUS treatment resulted in decreases in serum CRP, SAA, IL-6, IL-17A, IL-17F, & IL-22 that were significantly greater than PBO as early as Week 4 (FIG 1). These protein levels continued to decrease through Wk 24 in GUS-treated pts with both dosing regimens (p<0.05, geometric mean decrease from baseline ≥ 33%). Further, Wk 24 IL-17A & IL-17F levels for pts treated with either dose of GUS were not significantly different from healthy controls, suggesting a normalization of peripheral effector cytokines associated with the IL-23/Th17 axis following treatment with GUS. Effects on IL-17A/IL-17F were greater in GUS treated pts than UST treated pts, while CRP levels were similar in both programs (FIG 2).Conclusion:Comprising a strong pharmacodynamic effect, GUS treatment reduced serum protein levels of acute phase and Th17-effector cytokines (whose elevations at baseline were associated with PsA disease characteristics) and achieved comparable levels to those in healthy controls. In pts with PsA, reductions of IL-17A and IL-17F by GUS were of greater magnitude than those by UST.References:[1]Deodhar et al. ACR 2019, abs #807. Arth Rheumatol. 2019;71 S10: 1386[2]Mease et al. ACR 2019, abs #L13. Arth Rheumatol. 2019;71 S10:5247[3]Siebert et al. EULAR 2019, abs #479. Ann Rheum Dis. 2019;78 S2:293[4]Siebert et al. Arth Rheumatol. 2019;71:1660Acknowledgments:NoneDisclosure of Interests:Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Matthew J Loza Employee of: Janssen Research & Development, LLC, Keying Ma Employee of: Janssen Research & Development, LLC, Karen Leander, Employee of: Janssen Research & Development, LLC, Vani Lakshminarayanan Employee of: Janssen Research & Development, LLC, Carol Franks Employee of: Janssen Research & Development, LLC, Philip Cooper Employee of: Janssen Research & Development, LLC, Kristen Sweet Employee of: Janssen Research & Development, LLC

scholarly journals Efficacy of Tofacitinib for the Treatment of Psoriatic Arthritis: Pooled Analysis of Two Phase 3 Studies

2018 ◽  
Vol 5 (2) ◽  
pp. 567-582 ◽  
Author(s):  
Peter Nash ◽  
Laura C. Coates ◽  
Roy Fleischmann ◽  
Kim A. Papp ◽  
Juan Jesus Gomez-Reino ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Pooled Analysis ◽  
Phase 3 ◽  
Two Phase

THU0442 Reduction in Fatigue in Patients with Active Psoriatic Arthritis Are Sustained over 2 Years: Long-Term Results of Two Phase 3 Studies with Secukinumab

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 351.1-351
Author(s):  
L. Gossec ◽  
T.K. Kvien ◽  
P.G. Conaghan ◽  
M. Østergaard ◽  
J. Cañete ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Long Term Results ◽  
Phase 3 ◽  
Two Phase

Psoriatic Nail Dystrophy Is Associated with Erosive Disease in the Distal Interphalangeal Joints in Psoriatic Arthritis: A Retrospective Cohort Study

2019 ◽  
Vol 46 (9) ◽  
pp. 1097-1102 ◽  
Author(s):  
Anna S. Antony ◽  
Andrew Allard ◽  
Adwaye Rambojun ◽  
Christopher R. Lovell ◽  
Gavin Shaddick ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Joint Space Narrowing ◽  
Joint Space ◽  
Joint Disease ◽  
Nail Dystrophy ◽  
Chi Square ◽  
Convenience Sample ◽  
Radiographic Damage ◽  
Erosive Disease ◽  
Distal Interphalangeal

Objective.To assess whether the association between psoriatic nail dystrophy and radiographic damage in the hands of patients with psoriatic arthritis (PsA) is specific to the distal interphalangeal (DIP) joints.Methods.A convenience sample of patients was collated from the Bath longitudinal PsA cohort. All patients had PsA according to the ClASsification for Psoriatic ARthritis criteria (CASPAR) criteria, scored radiographs of their hands, and documented nail scores as measured by the Psoriatic Nail Severity Score. Chi-square tests were performed to examine for association between features of nail dystrophy and radiographic damage in the DIP joints, and proximal interphalangeal or metacarpophalangeal (non-DIP) joints of the corresponding digits.Results.There were 134 patients included, with a median age of 53 years (interquartile range; IQR 44–61) and disease duration of 7 years (IQR 3–17). The presence of any form of psoriatic nail dystrophy was associated with erosion at the DIP joints of the corresponding digit (OR 1.9, 95% CI 1.23–2.83; p < 0.004) and this association was primarily driven by the presence of nail onycholysis (OR 1.72; 95% CI 1.12–2.62; p = 0.02). Nail subungual hyperkeratosis was more strongly associated with joint space narrowing, erosions, and osteoproliferation at the corresponding DIP joint compared to non-DIP joints (p < 0.001). Nail pitting was not associated with erosions or osteoproliferation.Conclusion.The presence of psoriatic nail dystrophy, particularly onycholysis, is associated with erosive disease at the DIP joints. Subungual hyperkeratosis is more strongly associated with erosive damage at the DIP than non-DIP joints. These findings support the anatomical and pathological link between nail and DIP joint disease.

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