Optimization of Psoriatic and Seronegative Rheumatoid Arthritis Patients Selection and Treatment Outcomes of Biologic Therapies.
Study Details
Study Description
Brief Summary
Different classes of biological targeted therapies (b-DMARDs) are available for psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (RA) (TNF inhibitors, anti-IL23, anti-IL17). A variable percentage of subjects, however, does not respond the first b-DMARD. Musculoskeletal ultrasound (US) and synovial tissue analysis could provide useful information on the top of clinical variables to predict response. The primary aim of this project is to create a global single-cell RNA sequencing atlas of PsA synovitis and to evaluate the predictive value of clinical, US and synovial variables (inflammatory cells and synovial tissue-single cell signature) on disease trajectory outcome and treatment response.
Patients with PsA or seronegative RA at different disease stages will be enrolled. Clinical and US examination will be performed at baseline, 3, 6 and 12 months, while synovial biopsy at baseline and 6 months. The optimal combination of clinical, US and synovial variables to stratify treatment response will be developed. The sensitivity to change of US and synovial variables and their evaluation in patients achieving clinical remission will also be considered as secondary aims.
The expected results will help the optimisation of treatment strategies in patients with PsA and seronegative RA.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| PsO patients at risk of PsA development
|
Other: Phenotyping of synovial immune and stromal cells
Generate a comprehensive cellular and molecular atlas of PsA by CITE-Seq (single cell protein and transcriptomics) and spatial transcriptomics of synovium of PsO at risk of developing PsA and PsA patients across different disease stages.
|
| naive to treatment PsA
|
Other: Phenotyping of synovial immune and stromal cells
Generate a comprehensive cellular and molecular atlas of PsA by CITE-Seq (single cell protein and transcriptomics) and spatial transcriptomics of synovium of PsO at risk of developing PsA and PsA patients across different disease stages.
|
| TNF-inhibitor resistant PsA
|
Other: Phenotyping of synovial immune and stromal cells
Generate a comprehensive cellular and molecular atlas of PsA by CITE-Seq (single cell protein and transcriptomics) and spatial transcriptomics of synovium of PsO at risk of developing PsA and PsA patients across different disease stages.
|
| IL-17-inhibitor resistant PsA
|
Other: Phenotyping of synovial immune and stromal cells
Generate a comprehensive cellular and molecular atlas of PsA by CITE-Seq (single cell protein and transcriptomics) and spatial transcriptomics of synovium of PsO at risk of developing PsA and PsA patients across different disease stages.
|
| TNF-inhibitor induced remission PsA
|
Other: Phenotyping of synovial immune and stromal cells
Generate a comprehensive cellular and molecular atlas of PsA by CITE-Seq (single cell protein and transcriptomics) and spatial transcriptomics of synovium of PsO at risk of developing PsA and PsA patients across different disease stages.
|
| IL-17-inhibitor induced remission PsA
|
Other: Phenotyping of synovial immune and stromal cells
Generate a comprehensive cellular and molecular atlas of PsA by CITE-Seq (single cell protein and transcriptomics) and spatial transcriptomics of synovium of PsO at risk of developing PsA and PsA patients across different disease stages.
|
| c-DMARDs resistant PsA
|
Other: Phenotyping of synovial immune and stromal cells
Generate a comprehensive cellular and molecular atlas of PsA by CITE-Seq (single cell protein and transcriptomics) and spatial transcriptomics of synovium of PsO at risk of developing PsA and PsA patients across different disease stages.
|
| c-DMARDs resistant RA
|
Other: Phenotyping of synovial immune and stromal cells
Generate a comprehensive cellular and molecular atlas of PsA by CITE-Seq (single cell protein and transcriptomics) and spatial transcriptomics of synovium of PsO at risk of developing PsA and PsA patients across different disease stages.
|
Outcome Measures
Primary Outcome Measures
- Minimal Disease Activity status achievement [6 months]
This outcome will be recorded for all study cohorts
- PsA development (Fulfilment of the CASPAR criteria) [12 months]
This outcome will be recorded only for PsO patient with arthralgia at risk of PsA development
- Remission maintenance [12 months]
This outcome will be recorded only for PsA patients in sustained remission
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients fulfilling the CASPAR classification Criteria for PsA
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Patients fulfilling the 2010 ACR/EULAR classification criteria for RA
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Clinically active arthritis, with at least one joint clinically involved;
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Subject eligible to treatment (c-or b-DMARD) as indicated by the treating rheumatologist according to usual clinical practice
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Subjects with PsA in sustained clinical and ultrasound remission (MDA)
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Patients with PsO and arthralgia
Exclusion Criteria:
-
Severe and uncontrolled infections such as sepsis and opportunistic infections.
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Patients who are currently included in any interventional clinical trial in PsA or RA.
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Patients treated with more than one biologics.
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Subjects who are impaired, incapacitated, or incapable of completing study-related assessments
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Subjects with active vasculitis of a major organ system, with the exception of rheumatoid nodules.
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Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, whether or not related to RA or PsA and which, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study.
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Female subjects who have had a breast cancer screening that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded by additional clinical, laboratory, or other diagnostic evaluations.
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Subjects with a history of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ. Existing non-melanoma skin cell cancers should be removed, the lesion site healed, and residual cancer ruled out before administration of the study drug.
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Subjects who currently abuse drugs or alcohol.
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Subjects with evidence (as assessed by the investigator) of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of human immunodeficiency virus (HIV) detected during screening.
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Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months before the informed consent document was signed.
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Subjects who have received any live vaccines within 3 months of the anticipated first dose of study medication.
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Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any chronic bacterial infection (eg, chronic pyelonephritis, osteomyelitis, or bronchiectasis).
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Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be subjects with a history of active TB within the last 3 years, even if it was treated; a history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type; current clinical, radiographic, or laboratory evidence of active TB; and latent TB that was not successfully treated (≥ 4 weeks).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Division of Rheumatology | Rome | Italy | 00168 | |
| 2 | School of Immunity and Infection | Glasgow | United Kingdom |
Sponsors and Collaborators
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2784