Clinical trial NCT05567380: Comparative Study of Janus Kinase (JAK) Inhibitors Vs Tumor Necrosis Factor (TNF) Inhibitors in Rheumatoid Arthritis
Official title: Comparative Study of JAK Inhibitors Vs TNF Inhibitors in Patients With Rheumatoid Arthritis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Rheumatoid Arthritis
Keywords: JAK Inhibitors
TNF Inhibitors
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2022-10-05
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study will include all patients presented to the Rheumatology department-Sohag University Hospitals from October 1st , 2022 till June 30th , 2023, and were diagnosed with Rheumatoid Arthritis according to the 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology Classification Criteria for RA and received conventional DMARDs, TNF inhibitors (Golimumab or Etanercept) or JAK inhibitors (Barcitinib).

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.

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)

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of TJC and SJC
timeFrame: Change from baseline number of tender and swollen joint count at 6 months
measure: Assessment of Visual Analogue Scale (VAS)
timeFrame: Change from baseline Visual Analogue Scale (VAS) at 6 months
measure: Assessment of disease activity by DAS28 (Disease Activity Score for 28 Joints)
timeFrame: Change from baseline Disease Activity score for 28 joint (DAS28) at 6 months
measure: Clinical Disease Activity Index (CDAI) score.
timeFrame: Change from baseline Clinical Disease Activity Index at 6 months
measure: Structural joint damage
timeFrame: Change from baseline structural joint damage as measured by Larsen Scoring System at 6 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Sohag University
name: Esraa Mahmoud, MBBCh
role: PRINCIPAL_INVESTIGATOR
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