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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05567380
• Other study ID #: Soh-Med-22-09-06
• Status: Not yet recruiting
• Start date: October 2022
• Est. completion date: June 2023

Study information

• Verified date: October 2022
• Source: Sohag University
• Contact: Esraa Mahmoud, MBBCh
• Phone: +201016090864
• Email: esraamahmoud[@]med.sohag.edu.eg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: June 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sohag University

References & Publications (14)

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. Erratum in: Ann Rheum Dis. 2011 Aug;70(8):1520. — View Citation

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. — View Citation

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:ii111-5. doi: 10.1136/annrheumdis-2012-202576. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, Kvien TK, Navarro-Compán 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, Östör 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. Review. — View Citation

Smolen JS, Landewé 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. — View Citation

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. Erratum in: J Rheumatol. 2016 May;43(5):998. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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