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Effectiveness of Tofacitinib in the treatment of Rheumatoid Arthritis


There are several misconceptions around arthritis and rheumatoid arthritis. While arthritis refers to the inflammation of the joint caused by wear and tear, rheumatoid arthritis is an auto-immune disorder (1).The body’s immune system attacks tissues, mistaking them for a foreign pathogen.  Delayed diagnosis and treatment may lead to permanent joint damage or even heart disease. Timely diagnosis is critical to avoid long-term complications (1,2).


Rheumatoid arthritis affects the urban population more than the rural population. Approximately 0.70% of the Indian population is affected by this condition which translates to roughly 1.4 million Indians. The numbers are staggering. Gender-wise, females are more prone to rheumatoid arthritis than the male population (3).


Tofacitinib, a novel treatment option for rheumatoid arthritis


Tofacitinib (XELJANZ) is a novel treatment option approved by FDA to treat moderate to severe rheumatoid arthritis. It has proven to be useful in controlling the advancement of the condition. Tofacitinib is recommended in patients with rheumatoid arthritis who cannot tolerate one or more disease-modifying rheumatoid drugs (DMARDs) like Methotrexate. It can be prescribed as a monotherapy or in combination with methotrexate in patients with mild-to-moderate rheumatoid arthritis. The effectiveness of Tofacitinib in reducing pain and swelling is well-established in multiple clinical trials (4).


RA pathophysiology and the mechanism of action of Tofacitinib


The Janus kinase (JAK) enzymes are involved in innate and adaptive immune responses in immune-mediated inflammatory diseases. Janus kinases are a group of cytoplasmic tyrosine kinases and are classified into four subtypes; JAK1, JAK2, JAK3, and TYK2. These enzymes transduce cytokine-mediated signals via the JAK-STAT pathway. They can phosphorylate and activate downstream proteins involved in the signal transduction pathways (JAK-STAT pathways) (5,6). The cytokines attach themselves to the receptors on the immune cells and attack the joint capsule.


Janus Kinase Inhibitor, or JAK inhibitor, is an immune-modulating drug that can inhibit the activity of one or more Janus kinase enzymes by interfering with JAK-STAT pathways in lymphocytes. They are considered immune modulator molecules (5,8).


Tofacitinib inhibits intracellular signaling pathways mediated by cytokines involved in rheumatoid arthritis pathology. It helps to ease joint inflammation and pain. The JAK inhibitor dampens the hyperactive immune system that damages the joints causing inflammation and pain. 


Efficacy and Safety of Tofacitinib: Clinical evidence


The efficacy of Tofacitinib is well-established in multiple clinical trials. Data from 6 clinical trials with 4200 study participants demonstrated the efficacy of Tofacitinib in reducing joint pain and swelling and improving the ability to accomplish certain daily activity (9).

Data from the most recent landmark trial, The ORAL Solo Study provided more critical evidence on the efficacy of Tofacitinib. The study included adult patients with moderate to severe RA in whom biologic or nonbiologic DMARDs did not work well or could not be tolerated. Patients were prescribed Tofacitinib alone or just the placebo. Patients who received a placebo were switched to Tofacitinib at 3 months. The key finding were as follows (9):


  • At 2 weeks, 30% of patients on Tofacitinib had improvement in RA signs and symptoms vs 12% on placebo

  • At 3 months, more than half (59%) of patients on Tofacitinib had improvement in RA signs and symptoms vs 25% on placebo

  • At 3 months, 60% of patients on Tofacitinib had improvement in physical function vs 39% on placebo

  • At 6 months, 69% of patients on Tofacitinib had improvement


The ORAL Start & ORAL Scan Studies have further established the efficacy of Tofacitinib (9). Tofacitinib represents a new group of disease-modifying antirheumatic drugs that can be placed on an equal footing with the available biological drugs.  

Indications


Tofacitinib is prescribed for mild to moderate chronic RA (4). Besides RA, it is also prescribed for chronic inflammatory conditions like axial spondyloarthritis, psoriatic arthritis, ulcerative colitis, and atopic dermatitis (6).

Dosage


Immediate-release tablets are prescribed 5 mg orally twice daily for adults (7). If it is an extended-release tablet, the dosage is 11 mg orally once daily.  

About the Author


Dr. Abhaya Prabhu is a freelance medical writer with a passion for medical research and medical writing. She strives to write medical content that is accurate, engaging, and easy to understand. Her current focus is on Rheumatoid arthritis and new drugs that help in controlling the disease.


References


  1. Grassi W, De Angelis R, Lamanna G, et al. The clinical features of rheumatoid arthritis. Eur J Radiol. 1998 May;27 Suppl 1:S18-24

  2. Richard-Eaglin A, Smallheer BA. Immunosuppressive/Autoimmune Disorders. Nurs Clin North Am. 2018 Sep; 53(3):319-334.

  3. Malaviya AN, Kapoor SK, Singh RR, et al. Prevalence of rheumatoid arthritis in the adult Indian population. Rheumatol Int. 1993;13(4):131-4.

  4. Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA). Cochrane Database Syst Rev. 2016 Nov 17;11(11):CD012437

  5. Dhillon S. Tofacitinib: A Review in Rheumatoid Arthritis. Drugs. 2017 Dec; 77(18):1987-2001.

  6. Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017 Dec 28;17(1):78. 4.

  7. Fleischmann R, Mysler E, Hall S, et.al. ORAL Strategy investigators. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomized controlled trial. Lancet. 2017 Jul 29;390(10093):457-468

  8. Benjamin O, Goyal A, Lappin SL. Disease-Modifying Antirheumatic Drugs (DMARD). 2022 Jul 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 29939640.

  9. Xeljanz. Available at: https://www.xeljanz.com/ra/clinical-trials Accessed on 28 July, 2023  

Disclaimer


The matter published on this platform has been developed by independent medical writers from various healthcare backgrounds including members of MedWriters Alumni Network. Although great care has been taken in compiling and checking the information, the authors, Rxnews team and its partners or agents, and sponsors shall not be responsible or in any way liable for any errors, omissions, or inaccuracies in this blog article whether arising from negligence or otherwise, however or for any consequences arising therefrom. The inclusion and exclusion of any product do not mention that the publisher advocates or rejects its use generally or in any particular field or field. For any complaints or feedback please write to content@rxnews.in

 

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