Comparative Study of Janus Kinase (JAK) Inhibitors Vs Tumor Necrosis Factor (TNF) Inhibitors in Rheumatoid Arthritis

Sponsor

Sohag University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05567380

Collaborator

(none)

150

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Rheumatoid arthritis is a systemic autoimmune disease characterized by inflammatory synovitis and progressive joint destruction, which are associated with severe disability and increased mortality. It occurs at an incidence of 5 per 1000 with Women being 2 times more likely to be affected by Rheumatoid Arthritis than men. The peak incidence in both groups is in the sixth decade of life.

Management of RA has improved substantially in recent years. In addition to the reduction of signs and symptoms, improvement of physical function, and inhibition of structural damage, better patient outcomes, and clinical remission are now considered achievable goals. Therefore, the current recommended primary target for the treatment of RA should be a state of clinical remission.

Methotrexate (MTX) should be initiated, typically as monotherapy. If treatment response is inadequate, other Disease-modifying antirheumatic drugs (DMARDs) may be added to (rather than replacing) methotrexate to enhance efficacy and reduce the potential for the formation of anti-drug antibodies. TNF inhibitors are the first-line biologic therapies used in the event of incomplete response or adverse reaction to conventional DMARDs as TNF alpha is an important proinflammatory cytokine produced by macrophages and other cells, with myriad actions relevant to the pathogenesis of RA, including stimulation of other proinflammatory cytokine production, expression of endothelial cell adhesion molecules, production of metalloproteinases, and stimulation of osteoclasts. Activated Janus kinases (JAKs) play pivotal roles in intracellular signaling from cell-surface receptors for multiple cytokines implicated in the pathologic processes of rheumatoid arthritis. Baricitinib, an orally available small molecule, provides reversible inhibition of Janus Kinase 1 (JAK1) and Janus Kinase 2 (JAK2) and has shown clinical efficacy in studies involving patients with moderate to severely active Rheumatoid Arthritis who are either intolerant to MTX treatment or who have had an inadequate response to DMARDs, either conventional or biologic.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Other: Observation

Detailed Description

Aims of the Study:

To determine the outcome of patients with moderate to severely active rheumatoid arthritis (RA) - despite methotrexate treatment - on JAK inhibitors (Baricitinib).
To determine the outcome of patients with moderate to severely active rheumatoid arthritis (RA) - despite methotrexate treatment- on TNF inhibitors (Golimumab and Etanercept).
To compare the outcome between these 2 groups of patients in terms of improvements in signs and symptoms, physical function, patient-reported outcomes, and progression of structural joint damage.
Detection of any adverse effects that may emerge during the course of treatment.

Patients will be classified into 3 groups:

group (1): patients receiving Methotrexate group (2): patients receiving Methotrexate in addition to JAK inhibitors (Baricitinib at 4 mg once daily by oral route) group (3): patients receiving Methotrexate in addition to TNF inhibitors (Golimumab at 50 mg/month or Etanercept at 50mg/ week by subcutaneous injections)

Study Design

Study Type:

Observational

Anticipated Enrollment :

150 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Comparative Study of JAK Inhibitors Vs TNF Inhibitors in Patients With Rheumatoid Arthritis

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Methotrexate Patients newly diagnosed with active Rheumatoid Arthritis and receiving lowest effective dosage of Methotrexate as initial therapy.	Other: Observation Observation of Rheumatoid arthritis disease response to JAK inhibitors and TNF inhibitors after definite timepoints from the initialization of treatment in comparison to the current standard of care of therapy with conventional DMARDs.
Methotrexate + JAK Inhibitors Patients diagnosed with active Rheumatoid Arthritis and have shown intolerance or inadequate response to Methotrexate so JAK Inhibitor (Barcitinib) was added at 4mg/day orally to their therapy.	Other: Observation Observation of Rheumatoid arthritis disease response to JAK inhibitors and TNF inhibitors after definite timepoints from the initialization of treatment in comparison to the current standard of care of therapy with conventional DMARDs.
Methotrexate + TNF Inhibitors Patients diagnosed with active rheumatoid arthritis and have shown intolerance or inadequate response to Methotrexate so TNF Inhibitor was added to their therapy (either Golimumab at 50mg subcutaneous injection/m, or Etanercept at 50mg subcutaneous injection/wk)	Other: Observation Observation of Rheumatoid arthritis disease response to JAK inhibitors and TNF inhibitors after definite timepoints from the initialization of treatment in comparison to the current standard of care of therapy with conventional DMARDs.

Arm

Intervention/Treatment

Methotrexate

Patients newly diagnosed with active Rheumatoid Arthritis and receiving lowest effective dosage of Methotrexate as initial therapy.

Other: Observation

Observation of Rheumatoid arthritis disease response to JAK inhibitors and TNF inhibitors after definite timepoints from the initialization of treatment in comparison to the current standard of care of therapy with conventional DMARDs.

Methotrexate + JAK Inhibitors

Patients diagnosed with active Rheumatoid Arthritis and have shown intolerance or inadequate response to Methotrexate so JAK Inhibitor (Barcitinib) was added at 4mg/day orally to their therapy.

Other: Observation

Methotrexate + TNF Inhibitors

Patients diagnosed with active rheumatoid arthritis and have shown intolerance or inadequate response to Methotrexate so TNF Inhibitor was added to their therapy (either Golimumab at 50mg subcutaneous injection/m, or Etanercept at 50mg subcutaneous injection/wk)

Other: Observation

Outcome Measures

Primary Outcome Measures

Assessment of TJC and SJC [Change from baseline number of tender and swollen joint count at 6 months]
Assessment of Tender Joints Count (TJC) and Swollen Joints Count (SJC), both are parameters to describe disease severity.
Assessment of Visual Analogue Scale (VAS) [Change from baseline Visual Analogue Scale (VAS) at 6 months]
A patient is asked to indicate his/her perceived pain intensity along a 100 mm horizontal line, and this rating is then measured from the left edge. Minimum score is zero indicating no pain, while maximum score is 100 indicating severe pain.
Assessment of disease activity by DAS28 (Disease Activity Score for 28 Joints) [Change from baseline Disease Activity score for 28 joint (DAS28) at 6 months]
DAS28 (Disease Activity Score for 28 Joints) is a widely used scoring system for assessment of disease activity in Rheumatoid Arthritis patients. Minimum value is zero, which indicates disease remission while maximum value is 9.4, which indicates highest disease activity.
Clinical Disease Activity Index (CDAI) score. [Change from baseline Clinical Disease Activity Index at 6 months]
CDAI score is used in routine assessment of disease activity in RA patients. Minimum score is 0 indicating disease remission , while maximum score is 600 indicating highest disease activity.
Structural joint damage [Change from baseline structural joint damage as measured by Larsen Scoring System at 6 months]
measured by the modified Larsen scoring system using plain x-rays (AP view) on both hands and feet. Minimum score is zero indicating normal joint, while maximum score is 5 indicating complete joint deformation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age: patients >18 years old.
Patients with Rheumatoid arthritis diagnosed according to the 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology Classification Criteria for RA.
Patients with moderate to severely active RA as evaluated by DAS28-Score, who have never been treated with biologic DMARDs and who expressed a lack of adequate response or intolerability to conventional DMARDs.

Exclusion Criteria:

Age < 18 years.
Any autoimmune disease other than Rheumatoid arthritis.
Previous treatment with biologic DMARDs.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Sohag University

Investigators

Principal Investigator: Esraa Mahmoud, MBBCh, Sohag University

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Esraa Mohamed Mahmoud, Principal Investigator, Sohag University

ClinicalTrials.gov Identifier:

NCT05567380

Other Study ID Numbers:

Soh-Med-22-09-06

First Posted:

Oct 5, 2022

Last Update Posted:

Oct 12, 2022

Last Verified:

Oct 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Esraa Mohamed Mahmoud, Principal Investigator, Sohag University

JAK Inhibitors

TNF Inhibitors

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Study Results

No Results Posted as of Oct 12, 2022