Impact of serum interleukin-22 as a biomarker for the differential use of molecular targeted drugs in psoriatic arthritis: a retrospective study

Miyagawa, Ippei; Nakayamada, Shingo; Ueno, Makoto; Miyazaki, Yusuke; Iwata, S.; Kubo, Shunsuke; Sonomoto, Koshiro; Anan, Junpei; Ohkubo, Naoaki; Inoue, Yoshino; Tanaka, Yoshiya

doi:10.1186/s13075-022-02771-4

Cited by 7 publications

(5 citation statements)

References 25 publications

(15 reference statements)

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“…This is consistent with clinical findings that guselkumab is efficacious in both biologic‐naive and TNFi‐IR patient populations 23,24,26,37,38 . Previous research found that baseline IL‐22 levels were significantly lower in patients with PsA who achieved Disease Activity in Psoriatic Arthritis (DAPSA) remission after 1 year of therapy with an IL‐17 inhibitor than in those who did not, although IL‐22 levels were not associated with response to TNFi 39 . This previous work also showed that TNFα levels, but not IL‐17A or IL‐23 levels, were significantly higher at the initiation of bDMARD therapy in a group of patients characterized by high levels of IL‐22 relative to patients with low levels of IL‐22.…”

Section: Discussionsupporting

confidence: 87%

“…23,24,26,37,38 Previous research found that baseline IL-22 levels were significantly lower in patients with PsA who achieved Disease Activity in Psoriatic Arthritis (DAPSA) remission after 1 year of therapy with an IL-17 inhibitor than in those who did not, although IL-22 levels were not associated with response to TNFi. 39 This previous work also showed that TNFα levels, but not IL-17A or IL-23 levels, were significantly higher at the initiation of bDMARD therapy in a group of patients characterized by high levels of IL-22 relative to patients with low levels of IL-22. These findings suggest that unrestrained expression of TNFα and IL-22 may contribute to insufficient response to TNFi therapy in some patients.…”

Section: Discussionmentioning

confidence: 80%

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Modulation of Interleukin‐23 Signaling With Guselkumab in Biologic‐Naive Patients Versus Tumor Necrosis Factor Inhibitor–Inadequate Responders With Active Psoriatic Arthritis

Siebert,

Coates,

Schett

et al. 2024

Arthritis & Rheumatology

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ObjectiveAssess and compare immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)‐23p19‐subunit inhibitor, in participants with active PsA who were biologic‐naïve or had inadequate response to tumor necrosis factor inhibitors (TNFi‐IR).MethodsSerum biomarker levels at baseline and following treatment with guselkumab 100 mg Q8W were compared between biologic‐naïve (N=251) and TNFi‐IR (N=93) subgroups identified in the pooled DISCOVER‐1/DISCOVER‐2/COSMOS dataset. 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 subgroups.ResultsBaseline IL‐22, TNFα, and beta defensin (BD)‐2 levels were significantly lower in biologic‐naïve 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‐naïve 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‐naïve 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.ConclusionGuselkumab modulates IL‐23 signaling and provides consistent pharmacodynamic effects in both biologic‐naïve 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 with guselkumab suggest greater dysregulation of IL‐23/Th17 signaling in TNFi‐IR patients.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 80%

Modulation of Interleukin‐23 Signaling With Guselkumab in Biologic‐Naive Patients Versus Tumor Necrosis Factor Inhibitor–Inadequate Responders With Active Psoriatic Arthritis

Siebert,

Coates,

Schett

et al. 2024

Arthritis & Rheumatology

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“…For example, in PsA patients receiving the TNFi golimumab for active disease, higher baseline CRP levels were predictive of achievement of modified-minimal disease activity (mMDA) at 3 months, and were significantly associated with a higher probability of mMDA response at 6 months [ 38 ]. In PsA patients treated with IL-17i, baseline serum IL-22 levels were lower in those who achieved DAPSA remission compared with those who did not [ 39 ]. The current limited data on predictors of response across biomarker studies make it difficult to incorporate precision medicine in the management of PsA at this stage.…”

Section: Discussionmentioning

confidence: 99%

Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: results from the COSMOS phase 3b study

et al. 2023

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Background Guselkumab is a selective interleukin (IL)-23 inhibitor targeting the IL-23p19 subunit. In the phase 3b COSMOS trial, guselkumab demonstrated efficacy in treating participants with active psoriatic arthritis (PsA) and inadequate response (IR; lack of efficacy or intolerance) to tumor necrosis factor inhibitors (TNFi). Methods Adults with active PsA (≥ 3 swollen joints, ≥ 3 tender joints) and IR to one or two TNFi (TNFi-IR) were randomized 2:1 to guselkumab at Weeks 0, 4, then every 8 weeks (Q8W) or placebo➔guselkumab Q8W at Week 24 with possible early escape at Week 16. Levels of serum cytokines, including interferon ɣ (IFNɣ), IL-10, and tumor necrosis factor α (TNFα); T helper 17 (Th17) effector cytokines IL-17A, IL-17F, and IL-22; and acute phase proteins C-reactive protein (CRP), IL-6, and serum amyloid A (SAA), were assessed and compared with matched healthy controls; guselkumab pharmacodynamics through Week 24 were also assessed. Associations between baseline biomarker levels and 1) baseline disease activity (28-joint disease activity score using CRP [DAS28-CRP], psoriasis area and severity index [PASI], and % body surface area [BSA] affected by psoriasis) and 2) clinical response (including ≥ 20% improvement in American College of Rheumatology criteria [ACR20] response) at Week 24 were assessed. Results Baseline serum levels of IL-6, IL-10, IL-17A, IL-17F, IL-22, TNFα, and IFNɣ were significantly higher in COSMOS TNFi-IR participants than in matched healthy controls. Baseline IL-6, CRP, and SAA levels were associated with baseline DAS28-CRP. IL-17A and IL-17F levels were associated with baseline PASI score and psoriasis BSA. Baseline swollen or tender joint counts did not associate with baseline biomarker levels. At Week 24, significant decreases from baseline in CRP, SAA, IL-17A, IL-17F, and IL-22 levels were seen in guselkumab, but not placebo-, treated participants. IL-17F and IL-22 levels at Week 24 in guselkumab-treated participants did not significantly differ from those of matched healthy controls. Guselkumab-treated participants achieving ACR20 response at Week 24 exhibited higher baseline IL-22 and IFNɣ levels versus nonresponders. Conclusions Results from COSMOS participants with active, TNFi-IR PsA suggest guselkumab reduces levels of effector cytokines associated with the IL-23/IL-17 pathway, including those associated with baseline arthritis and skin disease activity. Trial registration ClinicalTrials.gov: NCT03796858.

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“…Regarding soluble biomarkers, the concentration of serum IL-22 has been recognized as a predictor of DAPSA-REM after one year of IL-17i therapy. 51 On the other hand, Shimauchi et al 52 evaluated serum levels of IL-22 and vascular endothelial growth factor (VEGF) and found that both were unable to predict response to treatment with ustekinumab or TNFi. In a prospective substudy, Wagner et al 53 analyzed baseline levels of 92 biomarkers in 100 patients from the GO-REVEAL trial investigating the response of PsA patients to golimumab.…”

Section: Precision Medicinementioning

confidence: 99%

Unmet needs in psoriatic arthritis, a narrative review

Lopez-Medina,

Kalyoncu,

Gossec

2024

Arch Rheumatol

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Psoriatic arthritis is a chronic rheumatic disease that poses challenges in its diagnosis, evaluation, and management. The heterogeneity in the manifestations and the absence of definitive diagnosis biomarkers often complicates the process of accurate diagnosis. Furthermore, the involvement of multiple disease domains poses difficulties in assessing disease activity and defining the concept of remission. Despite therapeutic advancements, a subset of patients remains refractory to treatment, leading to the emergence of the concept of “difficult-to-treat” patients and the necessity for novel therapeutic approaches (e.g., drugs with novel mechanisms of action; combinations of treatments). This review addresses key unmet needs in psoriatic arthritis, in terms of diagnosis, classification, evaluation, comorbidities and treatment.

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Impact of serum interleukin-22 as a biomarker for the differential use of molecular targeted drugs in psoriatic arthritis: a retrospective study

Cited by 7 publications

References 25 publications

Modulation of Interleukin‐23 Signaling With Guselkumab in Biologic‐Naive Patients Versus Tumor Necrosis Factor Inhibitor–Inadequate Responders With Active Psoriatic Arthritis

Modulation of Interleukin‐23 Signaling With Guselkumab in Biologic‐Naive Patients Versus Tumor Necrosis Factor Inhibitor–Inadequate Responders With Active Psoriatic Arthritis

Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: results from the COSMOS phase 3b study

Unmet needs in psoriatic arthritis, a narrative review

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