Evaluation of Pain Sensitization in Rheumatoid Arthritis: Analysis on a Cohort of Tofacitinib Treated Patients

NCT03815578 | Completed

• 1 other identifier: CHUBX 2017/39
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

Persistent pain and chronic fatigue are very common complaints in rheumatoid arthritis (RA) patients, whatever the anti-inflammatory treatment response. Interestingly, pain remaining despite good clinical response was associated with high disability and low inflammation at baseline, suggesting a mechanism of pain independent of inflammation in these patients. Such patients, with discordantly high patient-reported DAS28 components, fatigue and mood disturbance might represent a subgroup of RA patients who have specific clinical needs, not resolved by classical conventional or biologic DMARDs. In this way, neuropathic pain and pain sensitization have been demonstrated in 20 to 30% of RA patients, neuropathic pain scores being associated with worsen disease activity scores. Thus, pain sensitization may contribute to amplification of pain in active RA, and should be responsible for persisting pain and fatigue even after inflammation has resolved. Pain sensitization is associated with neuroplastic changes in sensory pathways at peripheral and central levels. Interestingly, major mediators responsible for this neuroplasticity operate via a JAK/STAT signaling pathway, which is specifically targeted by new RA treatments. New drug targeting JAK/STAT signalling pathway have been recently designed for RA treatment, based on the implication of this pathway on the signaling of various cytokines implicated in the pathophysiology of RA, such as IL-6, IL-12, IL-23 and IFNs. Two Jak-inhibitors have been put on the market: Tofacitinib and Baricitinib. In randomized clinical trials, Tofacitinib have shown a remarkable efficacy on pain and other patient reported outcomes, suggesting a specific effect or jak-inhibitors on pain control. Recent data suggest that Jak-inhibitors could have a direct effect on sensory neurons.

Conditions

Rheumatoid Arthritis

Keywords

pain sensitization; Tofacitinib; miRNA

Outcome Measures

Primary Outcomes (1)

• Variation of the mean Pressure Pain Thresholds (PPTs)

  At 6 months from baseline

Secondary Outcomes (14)

• Variation of Mechanical Temporal Summation (MTS)

  At 1, 3 and 6 months from baseline

• Variation of Pressure Pain Thresholds (PPTs)

  At 1, 3 and 6 months from baseline

• Variation of Diffuse noxious inhibitory control (DNIC) values

  At 1, 3 and 6 months from baseline

• Variation of Daily joint pain intensity

  At 1, 3 and 6 months from baseline

• Disease activity evaluated by the Disease Activity Score on 28 joints (DAS28)

  At 1, 3 and 6 months from baseline

Study Arms (1)

Rheumatoid Arthritis (RA) patients

EXPERIMENTAL

RA according to the ACR/EULAR 2010 classification criteria

Other: Clinical examination; Other: Pain assessment; Other: blood sample; Other: Patient Reported Outcomes

Interventions

Clinical examination OTHER

* Number of painful joints, * Number of swollen joints, * Patient Global assessment VAS (0 - 100) * and Physician Global assessment VAS (0 - 100)

Rheumatoid Arthritis (RA) patients

Pain assessment OTHER

* Pressure Pain Thresholds (PPTs), * Mechanical Temporal Summation (MTS) * and Diffuse Noxious Inhibitory Control (DNIC)

Rheumatoid Arthritis (RA) patients

blood sample OTHER

18 ml whole blood for ELISA analysis and miRNAs detection

Rheumatoid Arthritis (RA) patients

Patient Reported Outcomes OTHER

* Health Assessment Questionnaire (HAQ), * Rheumatoid Arthritis Impact of Disease score (RAID), * Daily joint pain intensity VAS (0-100), * Hospital Anxiety and Depression scale * and Coping Strategy Questionnaire.

Rheumatoid Arthritis (RA) patients

Eligibility Criteria

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

You may qualify if:

• Patients aged over 18 year-old ;
• Diagnosis of RA according to the ACR/EULAR 2010 classification criteria ;
• Patient eligible for tofacitinib treatment in agreement with European treatment labelling and French recommendation for RA treatment ;
• Oral prednisone intake is allowed until 10 mg, stable for at least 1 week at study entry ;
• Starting tofacitinib treatment for an active RA defined by a DAS28-ESR \> 3.2 ;
• Affiliated person or beneficiary of a social security scheme ;

You may not qualify if:

• Diagnosis of a systemic autoimmune disease other than RA ;
• Peripheral neuropathy ;
• Centrally-acting pain medications use within 3 months of enrolment (amitriptyline, gabapentin, duloxetine), or during the study ;
• Any opioid use within 1 month of enrolment or during the study ;
• Corticosteroid treatment over 10 mg of prednisone or equivalent ;
• Patient who present contraindications to tofacitinib treatment ;
• Patient presenting with a history of active tuberculosis or chronic infectious disease with a need of regular use of antibiotic ;
• Patients with active bacterial or viral infection, or presenting with an episode of infection that required treatment with antibiotics within 30 days prior to screening ;
• Patient presenting with a history of lymphoma or leukaemia or other malignancy besides non-melanoma skin cancer within 5 years ;
• Patient presenting with any uncontrolled medical condition ;
• Pregnancy or breast-feeding ;
• Patient unable to understand and follow recommendations or unable to perform self-evaluation ;
• Patient who refuse to participate to the study.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Pfizer: collaborator

Study Sites (2)

CHU de Bordeaux - Service de rhumatologie

Bordeaux, France

Location

CHU de Limoges - service de rhumatologie

Limoges, France

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Restraint, Physical; Blood Specimen Collection; Patient Reported Outcome Measures

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Behavior Control; Therapeutics; Immobilization; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Health Care Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Health Services Research; Health Planning; Health Care Economics and Organizations; Patient Outcome Assessment; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms; Public Health; Environment and Public Health

Study Officials

• Thierry SCHAEVERBEKE, Prof

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: January 24, 2019
• Study Start: June 17, 2019
• Primary Completion: April 28, 2023
• Study Completion: April 28, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)