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

NCT05567380 | Unknown DMC

• 1 other identifier: Soh-Med-22-09-06
• Study Type: observational
• Target: 150
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rheumatoid Arthritis

Keywords

JAK Inhibitors; TNF Inhibitors

Outcome Measures

Primary Outcomes (5)

• Assessment of TJC and SJC

  Assessment of Tender Joints Count (TJC) and Swollen Joints Count (SJC), both are parameters to describe disease severity.

  Change from baseline number of tender and swollen joint count at 6 months

• Assessment of Visual Analogue Scale (VAS)

  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.

  Change from baseline Visual Analogue Scale (VAS) at 6 months

• Assessment of disease activity by DAS28 (Disease Activity Score for 28 Joints)

  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.

  Change from baseline Disease Activity score for 28 joint (DAS28) at 6 months

• Clinical Disease Activity Index (CDAI) score.

  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.

  Change from baseline Clinical Disease Activity Index at 6 months

• Structural joint damage

  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.

  Change from baseline structural joint damage as measured by Larsen Scoring System at 6 months

Study Arms (3)

Methotrexate

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

Other: Observation

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

Interventions

Observation OTHER

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; Methotrexate + JAK Inhibitors; Methotrexate + TNF Inhibitors

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Sohag University: lead

Related Publications (14)

• Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet. 2007 Dec 1;370(9602):1861-74. doi: 10.1016/S0140-6736(07)60784-3.

  PMID: 17570481 BACKGROUND

• Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoid arthritis rising?: results from Olmsted County, Minnesota, 1955-2007. Arthritis Rheum. 2010 Jun;62(6):1576-82. doi: 10.1002/art.27425.

  PMID: 20191579 BACKGROUND

• Aletaha D, Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA. 2018 Oct 2;320(13):1360-1372. doi: 10.1001/jama.2018.13103.

  PMID: 30285183 BACKGROUND

• Ting YT, Petersen J, Ramarathinam SH, Scally SW, Loh KL, Thomas R, Suri A, Baker DG, Purcell AW, Reid HH, Rossjohn J. The interplay between citrullination and HLA-DRB1 polymorphism in shaping peptide binding hierarchies in rheumatoid arthritis. J Biol Chem. 2018 Mar 2;293(9):3236-3251. doi: 10.1074/jbc.RA117.001013. Epub 2018 Jan 9.

  PMID: 29317506 BACKGROUND

• O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013 Apr;72 Suppl 2(0 2):ii111-5. doi: 10.1136/annrheumdis-2012-202576.

  PMID: 23532440 BACKGROUND

• Kitas GD, Gabriel SE. Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives. Ann Rheum Dis. 2011 Jan;70(1):8-14. doi: 10.1136/ard.2010.142133. Epub 2010 Nov 24.

  PMID: 21109513 BACKGROUND

• Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, Kvien TK, Navarro-Compan MV, Oliver S, Schoels M, Scholte-Voshaar M, Stamm T, Stoffer M, Takeuchi T, Aletaha D, Andreu JL, Aringer M, Bergman M, Betteridge N, Bijlsma H, Burkhardt H, Cardiel M, Combe B, Durez P, Fonseca JE, Gibofsky A, Gomez-Reino JJ, Graninger W, Hannonen P, Haraoui B, Kouloumas M, Landewe R, Martin-Mola E, Nash P, Ostergaard M, Ostor A, Richards P, Sokka-Isler T, Thorne C, Tzioufas AG, van Vollenhoven R, de Wit M, van der Heijde D. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016 Jan;75(1):3-15. doi: 10.1136/annrheumdis-2015-207524. Epub 2015 May 12.

  PMID: 25969430 BACKGROUND

• Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O'Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T; American College of Rheumatology. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2016 Jan;68(1):1-25. doi: 10.1002/acr.22783. Epub 2015 Nov 6.

  PMID: 26545825 BACKGROUND

• Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, Emery P, Gaujoux-Viala C, Gossec L, Nam J, Ramiro S, Winthrop K, de Wit M, Aletaha D, Betteridge N, Bijlsma JW, Boers M, Buttgereit F, Combe B, Cutolo M, Damjanov N, Hazes JM, Kouloumas M, Kvien TK, Mariette X, Pavelka K, van Riel PL, Rubbert-Roth A, Scholte-Voshaar M, Scott DL, Sokka-Isler T, Wong JB, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014 Mar;73(3):492-509. doi: 10.1136/annrheumdis-2013-204573. Epub 2013 Oct 25.

  PMID: 24161836 BACKGROUND

• Brennan FM, McInnes IB. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest. 2008 Nov;118(11):3537-45. doi: 10.1172/JCI36389.

  PMID: 18982160 BACKGROUND

• Burmester GR, Kaeley GS, Kavanaugh AF, Gabay C, MacCarter DK, Nash P, Takeuchi T, Goss SL, Rodila R, Chen K, Kupper H, Kalabic J. Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab. RMD Open. 2017 Sep 17;3(2):e000465. doi: 10.1136/rmdopen-2017-000465. eCollection 2017.

  PMID: 28955494 BACKGROUND

• Tanaka Y, Emoto K, Cai Z, Aoki T, Schlichting D, Rooney T, Macias W. Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study. J Rheumatol. 2016 Mar;43(3):504-11. doi: 10.3899/jrheum.150613. Epub 2016 Feb 1.

  PMID: 26834213 BACKGROUND

• Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, Beattie SD, Koch AE, Cardillo TE, Rooney TP, Macias WL, de Bono S, Schlichting DE, Smolen JS. Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247.

  PMID: 27028914 BACKGROUND

• Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, Lee CH, Fidelus-Gort RK, Luchi ME, Rooney TP, Macias WL, Genovese MC. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis. 2015 Feb;74(2):333-40. doi: 10.1136/annrheumdis-2014-206478. Epub 2014 Nov 27.

  PMID: 25431052 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Observation

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)

Methods; Investigative Techniques

Study Officials

• Esraa Mahmoud, MBBCh

  Sohag University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Esraa Mahmoud, MBBCh

CONTACT

+201016090864; esraamahmoud@med.sohag.edu.eg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 22, 2022
• First Posted: October 5, 2022
• Study Start: October 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: June 1, 2023
• Last Updated: October 12, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share