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

NCT ID: NCT03815578

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-17
• Study Completion Date: 2023-04-28

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Rheumatoid Arthritis (RA) patients

RA according to the ACR/EULAR 2010 classification criteria

Group Type: EXPERIMENTAL

Clinical examination

Intervention Type: OTHER

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

Pain assessment

Intervention Type: OTHER

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

blood sample

Intervention Type: OTHER

18 ml whole blood for ELISA analysis and miRNAs detection

Patient Reported Outcomes

Intervention Type: 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.

Interventions

Clinical examination

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

Intervention Type: OTHER

Pain assessment

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

Intervention Type: OTHER

blood sample

18 ml whole blood for ELISA analysis and miRNAs detection

Intervention Type: OTHER

Patient Reported Outcomes

• 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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients aged over 18 year-old ;
• Diagnosis of RA according to the ACR/EULAR 2010 classification criteria ;
• Active rheumatoid arthritis defined by a Disease Activity Score (DAS28) > 3.2 at inclusion ;
• 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 ;
• Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research).

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thierry SCHAEVERBEKE, Prof

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Locations

CHU de Bordeaux - Service de rhumatologie

Bordeaux, , France

CHU de Limoges - service de rhumatologie

Limoges, , France

Countries

France

Other Identifiers

CHUBX 2017/39

Identifier Type: -

Identifier Source: org_study_id