Retention rates and identification of factors associated with anti-TNFα, anti-IL17, and anti-IL12/23R agents discontinuation in psoriatic arthritis patients: results from a real-world clinical setting

Navarini, Luca; Costa, Luisa; Tasso, Marco; Chimenti, Maria Sole; Currado, Damiano; Fonti, Giulia Lavinia; Ciccozzi, Massimo; Margiotta, Domenico Paolo Emanuele; Benigno, Carolina; Martino, Erica De; Perricone, Roberto; Afeltra, Antonella; Scarpa, Raffaele; Caso, Francesco

doi:10.1007/s10067-020-05027-1

Cited by 19 publications

(26 citation statements)

References 28 publications

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“…PsA treatment efficacy and persistence may be greater with shorter disease duration,18 45 perhaps because PsA disease burden, including decreased physical function, improves to a greater extent during early disease 46. Here, guselkumab treatment effect was retained regardless of PsA disease duration <1 year, ≥1–<3 years or ≥3 years.…”

Section: Discussionmentioning

confidence: 79%

“…A similar effect of decreased efficacy in obese patients with PsA was observed in post-hoc analyses from two phase III studies of the Janus kinase (JAK) inhibitor, tofacinitib 16. Patient sex also correlates with treatment persistence,17–19 as does inadequate response to biologicals, with the use of each subsequent biological yielding successively lower rates of drug persistence 17 19–21. However, the difficult-to-treat inadequate responder subpopulation may initially experience greater efficacy responses by switching to an alternative biological following failure of ≥1 TNFi 22.…”

Section: Introductionmentioning

confidence: 70%

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Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies

et al. 2022

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ObjectivesTo evaluate the efficacy through 52 weeks of guselkumab, an interleukin 23-p19 subunit inhibitor, in subgroups of pooled psoriatic arthritis (PsA) patients from the DISCOVER-1 and DISCOVER-2 trials defined by baseline patient characteristics.MethodsAdults with active PsA despite standard therapies were enrolled in DISCOVER-1 (≥3 swollen and ≥3 tender joints, C reactive protein (CRP) level ≥0.3 mg/dL) and DISCOVER-2 (≥5 swollen and ≥5 tender joints, CRP ≥0.6 mg/dL, biological-naïve). Randomised patients received 100 mg guselkumab at weeks 0, 4, and then every 4 or 8 weeks (Q4W/Q8W) or placebo. Guselkumab effects on joint (ACR20/50/70), skin (IGA 0/1, IGA 0), patient-reported outcome (Health Assessment Questionnaire Disability Index/Functional Assessment of Chronic Illness Therapy-Fatigue) and disease severity (minimal disease activity/PsA Disease Activity Score low disease activity) endpoints were evaluated by patient sex, body mass index, PsA duration, swollen/tender joint counts, CRP level, percent body surface area with psoriasis, Psoriasis Area and Severity Index score, and conventional synthetic disease-modifying antirheumatic drug use at baseline.ResultsBaseline patients characteristics in DISCOVER-1 (N=381) and DISCOVER-2 (N=739) were well balanced across randomised groups. At week 24, 62% (232/373) and 60% (225/375), respectively, of guselkumab Q4W-treated and Q8W-treated patients pooled across DISCOVER-1 and DISCOVER-2 achieved the primary endpoint of ACR20 response versus 29% (109/372) of placebo-treated patients. Guselkumab treatment effect at week 24 was observed across patient subgroups. Within each patient subgroup, response rates across all disease domains were sustained or increased at week 52 with both guselkumab regimens.ConclusionsGuselkumab Q4W and Q8W resulted in robust and sustained improvements in PsA signs and symptoms consistently in subgroups of patients defined by diverse baseline characteristics.Trial registration numbersNCT03162796, NCT03158285.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 70%

Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies

et al. 2022

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“…Li and colleagues (Li et al, 2005) have shown that expression and regulation of mPGES‐1 and PPAR‐γ in human osteoarthritic cartilage and chondrocytes are regulated by pro‐inflammatory stimuli such as IL‐1α and TNF‐α and that the concomitant presence of IL‐17 displayed a synergistic effect, reversed by troglitazone or exogenous PGE 2 . These data suggest that mPGES‐1 may prove to be an interesting therapeutic target for controlling PGE 2 synthesis in certain IMIDs such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondylarthritis (SpA) (Jouzeau et al, 2008; Navarini et al, 2020) where IL‐17 levels are uniquely situated to amplify inflammation (Maione, 2016).…”

Section: Discussionmentioning

confidence: 99%

IL‐17‐induced inflammation modulates the mPGES‐1/PPAR‐γ pathway in monocytes/macrophages

Raucci

Saviano

Casillo

et al. 2021

British J Pharmacology

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Background and Purpose Recent biochemical and pharmacological studies have reported that in several tissues and cell types, microsomal PGE2 synthase (mPGES) and PPAR‐γ expression are modulated by a variety of inflammatory factors and stimuli. Considering that very little is known about the biological effects promoted by IL‐17 in the context of mPGES‐1/PPAR‐γ modulation, we sought to investigate the contribution of this unique cytokine on this integrated pathway during the onset of inflammation. Experimental Approach We evaluated effects of PF 9184 (mPGES‐1 inhibitor) and troglitazone (PPAR‐γ agonist) in vitro, using the mouse macrophage cell line J774A.1. In vivo, the dorsal air pouch model in CD1 mice was used, and inflammatory infiltrates were analysed by flow cytometry. Locally produced cyto‐chemokines and PGs were assessed using elisa assays. Western blots were also employed to determine the activity of various enzymes involved in downstream signalling pathways. Key Results PF 9184 and troglitazone, in a time‐ and dose‐dependent manner, modulated leukocyte infiltration, myeloperoxidase activity, and the expression of COX‐2/mPGES‐1, NF‐кB/IкB‐α, and mPTGDS‐1/PPAR‐γ, induced by IL‐17. Moreover, both PF 9184 and troglitazone modulated PG (PGE2, PGD2, and PGJ2) production, the expression of different pro‐inflammatory cyto‐chemokines, and the recruitment of inflammatory monocytes, in response to IL‐17. Conclusions and Implications Our data suggest that IL‐17 may constitute a specific modulator of inflammatory monocytes during later phases of the inflammatory response. The results of this study show, for the first time, that the IL‐17/mPGES‐1/PPAR‐γ pathway could represent a potential therapeutic target for inflammatory‐based and immune‐mediated diseases. LINKED ARTICLES This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc

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“…4 Cure and elimination of medication is not considered possible for the vast majority of patients, with studies reporting a medication discontinuation rate due to sustained remission of only 1.7%. 5 Lifestyle modifications are recommended and concentrate on reducing weight if required, smoking cessation, and regular physical activity. 3 Yet the case presented suggests that dietary modifications may play a role in sustaining remission and aiding the discontinuation of medication.…”

Section: Discussionmentioning

confidence: 99%

Managing Psoriatic Arthritis With a Whole Food Plant-Based Diet: A Case Study

Lewandowska

Dunbar

Kassam

2021

American Journal of Lifestyle Medicine

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A 40-year-old female teacher presented to the rheumatology clinic in 2003 with nonspecific back, knees, and right ankle pain. She was subsequently diagnosed with psoriatic arthritis and was taking methotrexate to control her disease. Over the years, her symptoms were mostly under control. However, in 2018, after adopting a whole food plant-based diet free of added salt, oil, and sugar, she was able to stop taking methotrexate. She was discharged from the rheumatology clinic and has remained symptom-free since. The available literature on managing psoriatic arthritis with diet shows that less than 2% of patients with psoriatic arthritis are able to discontinue medication as a result of disease remission. This case report adds to support and encourages further research in the field of managing inflammatory polyarthropathies with diet and lifestyle.

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Retention rates and identification of factors associated with anti-TNFα, anti-IL17, and anti-IL12/23R agents discontinuation in psoriatic arthritis patients: results from a real-world clinical setting

Cited by 19 publications

References 28 publications

Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies

Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies

IL‐17‐induced inflammation modulates the mPGES‐1/PPAR‐γ pathway in monocytes/macrophages

Managing Psoriatic Arthritis With a Whole Food Plant-Based Diet: A Case Study

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