Reconstitution of CD4+CD25highCD127low/-Tcell

NCT03736044 | Completed DMC

• 1 other identifier: PRUa1GR-2013 -00000156
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

Rheumatoid arthritis (RA) is a systemic disabling inflammatory disease, of autoimmune origin characterized by chronic synovial inflammation resulting in joint damage. Treg cell function in patients with active RA is assumed to be impaired, a trend that seems to be reversed by TNFalpha antagonist therapy. Remission is the current treatment goal in RA. An increasing number of patients in clinical trials achieve this goal raising the question whether patients who have been in remission for a prolonged period (sustained remission) still need medication indefinitely. From a decade TNF-blocker therapy have represented a new treatment option for RA patients non responders to conventional DMARDs and some evidence are now available showing that sustainable remission can be maintained achieved after withdrawal of TNF blocker. Objectives: to verify whether in RA patients in prolonged clinical and instrumental remission the percentages of CD4+CD25highCD127low/- T cells could represent a reliable marker of immunological remission and, even more relevant, if the pharmacological reconstitution of this "immune-modulator" Tcell population could contribute to better identify patients with a low risk of relapse after cessation of TNF-blocker therapy. Methods: in RA patients, who fulfilled the 1987 ACR revised criteria, with disease duration ! 5 years, clinical \[Disease Activity Score on 28 joints-DAS28 0.56 ×√(TJC28) + 0.28×√(SJC28) + 0.70×ln(ESR) + 0.014×GH.TJC= Tender Joints Count (from 0 to 28); SJC= Swollen Joints Count (from 0 to 28) ESR=Erythrocyte Sedimentation Rate GH= patient's assessment of general health (VAS range from 0 to 100 mm); disease's flare was considered if: DAS44 \>=2.4/DAS28 \>=3.2.)\], instrumental (joint ultrasonography: sites to be explored wrists are II-III metacarpophalangeal joint bilaterally using Power Doppler signal (grading 0-3); any other joint will be studied if symptomatic) and immunological (circulating CD4+CD25highCD127low/-Tcells and inflammatory cytokines levels) examination will be performed in order to asses, at different levels, disease activity status. Expected results: to identify in RA patients treated with anti-TNF an "exit-strategy" from these drugs based on clinical, imaging and immunologic features indicative of a sustained remission and to verify whether such conditions are able to predict a low incidence of relapse.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Remission; T regulatory lymphocytes; Tumor Necrosis Factor-blocker therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects who flare-up after cessation of anti-TNF therapy after 24 months

  disease flare-up defined as DAS 28 \>3.2

  24 months

Secondary Outcomes (6)

• Proportion of subjects who are still in remission or il low disease activity after 3, 6, 9, 12, 15, 18, 21, 24 months

  24 months

• Swollen joint counts after 3, 6, 9, 12, 15, 18, 21, 24 months

  24 months

• Tender joint counts after 3, 6, 9, 12, 15, 18, 21, 24 months

  24 months

• Patient self assessment of pain (VAS) after 3, 6, 9, 12, 15, 18, 21, 24 months

  24 months

• Physician's and patient's assessment of global disease activity (VAS) after 3, 6, 9, 12, 15, 18, 21, 24 months

  24 months

Study Arms (2)

TNF-blockers withdrawal

EXPERIMENTAL

Patients on treatment with TNF-blockers plus DMARDs in which a withdrawal of anti-TNF therapy was made.

Drug: TNF-blockers suspension in patients with rheumatoid arthritis

DMARDs control group

NO INTERVENTION

Patients treated with DMARDs only (Methotrexate/Leflunomide), never treated with anti-TNF.

Interventions

TNF-blockers suspension in patients with rheumatoid arthritis DRUG

in patients treated with anti-TNF the intervention consisted in anti-TNF drug withdrawal, after a preliminary careful examination of remission status; a 18 months (at least) follow up was performed.

TNF-blockers withdrawal

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with RA fulfilling the 1987 ACR classification criteria (10) treated with anti-TNF and/or conventional DMARDs for at least 12 months, in prolonged remission (DAS28 \<2.6 or DAS44 \<1.6) for at least 6 months (checked in two consecutive visits 3 months apart), without Glucocorticosteroid (for at least 3 months, before), on a stable treatment for at least 3 months.

You may not qualify if:

• assumption of glucocorticosteroids within the three months before; confounding comorbidities such as fibromyalgia; chronic inflammatory disease other than RA; ongoing infections at the time of enrolment; recent trauma.

Sponsors & Collaborators

• University Hospital of Ferrara: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Rheumatology Physician assistant/Principal investigator

Model Details: * Group A: patients on treatment with TNF-blockers plus DMARDs * Group B: patients treated with DMARDs only (Methotrexate/Leflunomide), never treated with anti-TNF. In addition a cohort of healthy subjects matched for sex and age used as a control.

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: November 8, 2018
• Study Start: November 25, 2013
• Primary Completion: March 13, 2017
• Study Completion: March 13, 2017
• Last Updated: November 8, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share