Targeted Therapies in Psoriatic Arthritis—An Update

Sundanum, Sonia; Orr, Carl; Veale, Douglas

doi:10.3390/ijms24076384

Cited by 9 publications

(4 citation statements)

References 141 publications

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“…No differences were retrieved about IL-23/IL-17-pathway in these patients. The prominent role of this inflammatory axis has been proposed in this context of psoriatic disease ( 10 ). More specifically, IL-23 is a cytokine member of IL-12 superfamily, showing both immunoregulatory activity and effector functions ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Cytokine profile characterization of naïve patients with psoriasis and psoriatic arthritis: implications for a pathogenic disease continuum

et al. 2023

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BackgroundThe idea of psoriatic disease continuum has been progressively prompted based on the advances of the knowledge about the pathogenic steps underpinning the occurrence of psoriasis (PSO) and psoriatic arthritis (PSA). To evaluate biomolecules (inflammatory cytokines, inflammatory chemokines, cell adhesion and cellular mediators) in naïve patients with PSO, PSA with PSO, and PSA sine PSO. To stratify the results considering the presence of psoriatic nail involvement, extensive skin disease and obesity evaluating all involved patients.MethodsBy multiplex technology, 20 serum biomolecules were assessed with the inclusion of pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-12p70, IL-17A, IL-23, TNF), anti-inflammatory cytokines (IFN-α, IL-4, IL-10, IL-13), inflammatory chemokines (IP-10, MCP-1, MIP-1α, MIP-1β), cell adhesion and cellular mediators (ICAM-1, E-selectin, P-selectin). The assessment of possible statistical differences between the means of the three groups was performed by One-Way ANOVA. In addition, by non-parametric T-tests, we stratified the results according to selected clinical characteristics (psoriatic nail involvement, PASI ≥ 10, BMI ≥ 30).ResultsIn 80 assessed naïve patients, patients with PSO showed significant increases of E-selectin (p=0.021) and IL-8 (0.041) than other groups. In patients with PSA with PSO, significant higher levels of ICAM-1 were observed (p=0.009) than other groups. We did not observe further differences comparing pro-inflammatory and anti-inflammatory cytokines, inflammatory chemokines, and cell adhesion and cellular mediators in patients with PSO, PSA with PSO, and PSA sine PSO. Patients with psoriatic onychopathy showed significant increased levels of ICAM-1 (p=0.010) and IP-10 (0.030) than others. In patients with PASI ≥ 10, significantly enhanced values of IL-8 (p=0.004), TNF (p=0.013), E-selectin (p=0.004), MIP-1α (p=0.003), and MIP-1β (p=0.039). In patients with BMI ≥ 30, significantly higher levels of E-selectin were pointed out (p=0.035) than others.ConclusionOur findings may suggest that a similar cytokine profile may characterize naïve patients with PSO, PSA with PSO, and PSA sine PSO, reinforcing the concept of psoriatic disease continuum. However, some differences may be also shown, underlying possible pathogenic differences and leading to the clinical heterogeneity of these patients.

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Section: Discussionmentioning

confidence: 99%

Cytokine profile characterization of naïve patients with psoriasis and psoriatic arthritis: implications for a pathogenic disease continuum

et al. 2023

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“…TNFi, a class of pharmaceuticals that antagonize TNF-α activity, have shown efficacy in the management of PsA. These medications, including etanercept, certolizumab pegol, infliximab, adalimumab, and golimumab, decrease joint inflammation, improve physical function, and prevent joint damage in patients with PsA [79]. TNFi have shown significant efficacy in treating all SpA manifestations and are recommended by the GRAPPA and EULAR for the management of enthesitis and dactylitis [80].…”

Section: Tnf-α Inhibitors In Psamentioning

confidence: 99%

Inflammatory Cytokines in Psoriatic Arthritis: Understanding Pathogenesis and Implications for Treatment

Lee

Moon

2023

IJMS

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Psoriatic arthritis (PsA) is a persistent, inflammatory disease that affects individuals with psoriasis, arthritis, and enthesitis. Research has demonstrated that inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23), and interleukin-17 (IL-17) play a pivotal role in both the onset and progression of PsA. These cytokines are generated by activated immune cells and stimulate the attraction of inflammatory cells to the synovium and joint tissues, resulting in the deterioration of cartilage and bone. The blocking of these cytokines has become a successful treatment strategy for PsA, as biological drugs that inhibit TNF-α, IL-23, and IL-17 have demonstrated notable clinical benefits. The association between PsA and other types of inflammatory cytokines or chemokines, excluding TNF-α, IL-23, and IL-17, has been extensively investigated in numerous studies. These findings may provide a chance for the discovery of novel therapeutic agents targeting other molecules, distinct from the currently approved biologics and targeted synthetic disease-modifying anti-rheumatic drugs. In this review, we discuss the current understanding of the role of inflammatory cytokines in PsA pathogenesis and clinical implications of targeting these cytokines for PsA treatment.

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“…[1][2][3] Given the potential of severe and widespread organ damage, SRDs are associated with a considerable disease burden globally [4][5][6] despite advances in the treatment landscape of SRDs. [7][8][9][10][11] There is an urgent need for changes in current therapies and the development of new approaches.…”

Section: Introductionmentioning

confidence: 99%

“…Interactions between genetic and environmental factors may contribute to triggering immune pathways, producing multiple autoantibodies and inflammatory factors and finally causing damage to multiple organs . Given the potential of severe and widespread organ damage, SRDs are associated with a considerable disease burden globally despite advances in the treatment landscape of SRDs . There is an urgent need for changes in current therapies and the development of new approaches.…”

Section: Introductionmentioning

confidence: 99%

Control Groups in RCTs Supporting Approval of Drugs for Systemic Rheumatic Diseases, 2012-2022

Liu,

Xie,

Qin

et al. 2023

JAMA Netw Open

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ImportanceRandomized clinical trials (RCTs) testing innovative drugs must strive to use optimal control groups to reflect the best available treatments. A comprehensive evaluation of the quality of control groups in pivotal RCTs supporting systemic rheumatic disease (SRD) drug approvals by the Food and Drug Administration (FDA) is lacking.ObjectiveTo examine the proportion of pivotal RCTs that used optimal control groups among RCTs supporting newly approved SRD drugs in the US over the past decade.Design, Setting, and ParticipantsIn this study, individual RCTs supporting SRD new drug approvals by the FDA between January 2012 and October 2022 were analyzed for design, study duration, control group, and primary end point. The quality of control groups was determined by comparison with published guidelines before and during the trial.Main Outcomes and MeasuresThe primary measure was the proportion of RCTs using optimal control groups. Differences in response rate between investigating and control groups and the response rate of placebo control groups were also examined.ResultsBetween January 2012 and October 2022, the FDA approved 44 SRD drugs, involving 65 pivotal RCTs. Overall, 16 RCTs used optimal control groups. In 55 trials, no active groups were used, and more than 80% of these trials were suboptimal (47 trials [85.5%]). Among 56 trials for systemic arthritis, 49 trials used suboptimal control groups, mainly placebo or dose-response controls (47 trials), with a few active controls (2 trials). Studies of other SRDs frequently used placebo or dose-response controls but were considered optimal controls (8 trials). There was significant improvement in response rates of investigating compared with placebo groups, with relative risk mostly exceeding 1.50 (range, 0.90; 95% CI, 0.69-1.17 for anifrolumab to 11.00; 95% CI, 2.69-44.96 for mepolizumab). In all placebo-controlled trials, the median (IQR) response rate in placebo groups was 26.0% (19.2%-32.3%).Conclusions and RelevanceThese findings suggest that the quality of control groups in RCTs leading to SRD drug approval needs improvement and that despite challenges in translating scientific theories to clinical scenarios, it is crucial to consistently prioritize efforts to promote appropriate control group selection to ensure the accurate assessment of innovative drug efficacy.

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Targeted Therapies in Psoriatic Arthritis—An Update

Cited by 9 publications

References 141 publications

Cytokine profile characterization of naïve patients with psoriasis and psoriatic arthritis: implications for a pathogenic disease continuum

Cytokine profile characterization of naïve patients with psoriasis and psoriatic arthritis: implications for a pathogenic disease continuum

Inflammatory Cytokines in Psoriatic Arthritis: Understanding Pathogenesis and Implications for Treatment

Control Groups in RCTs Supporting Approval of Drugs for Systemic Rheumatic Diseases, 2012-2022

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