Pfizer's Innovative Oral JAK Inhibitor Xeljanz® (Tofacitinib Citrate Tablets) Receives New Indication Approval in China for Active Psoriatic Arthritis

On October 26, according to a post on Pfizer's WeChat Official Account, the National Medical Products Administration (NMPA) of China approved Xeljanz® (tofacitinib citrate tablets) on October 11, 2022, and tofacitinib citrate extended-release tablets on October 18, 2022, for adult patients with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). The simultaneous approval of both immediate-release and extended-release formulations will provide new treatment options for PsA patients in China. The recommended dosage for Xeljanz® (tofacitinib citrate tablets) immediate-release formulation is 5mg each time, twice daily; the recommended dosage for Xeljanz® extended-release formulation (tofacitinib citrate extended-release tablets) is 11mg each time, once daily.

As the first pharmaceutical company in the world to develop the JAK (Janus kinase) pathway for inflammatory and immune diseases, Pfizer has been exploring the clinical application value of JAK inhibitors for over 30 years. In 2000, Pfizer screened out the JAK inhibitor tofacitinib from more than 1,000 compounds. In 2017, Xeljanz® (tofacitinib citrate tablets), the world’s first oral JAK inhibitor for the treatment of rheumatoid arthritis, was approved in China for the treatment of moderate to severe rheumatoid arthritis, with expanding indications for the treatment of active ankylosing spondylitis and active psoriatic arthritis.

JAK Inhibitors Show Promise for PsA Patients

Unmet Clinical Needs

PsA is a chronic inflammatory immune-mediated arthritis characterized by joint inflammation and damage, psoriatic skin lesions, enthesitis, dactylitis, spondylitis, progressive disability, and adverse impact on quality of life1,2.

In the 2010 published guidelines for the diagnosis and treatment of PsA, the reported prevalence rate was 0.123%3. Patient-reported outcomes reflect that the disease has caused significant functional impairment in Chinese patients, with approximately 30%-40% of patients reporting PsA-related unemployment, and one-third of patients reporting a reduction in income4,5. PsA also imposes a substantial economic burden5 and psychological burden; in China, about 20%-30% of PsA patients suffer from anxiety and depression6.

Traditional synthetic disease-modifying antirheumatic drugs (csDMARDs) are recommended as the first-line treatment for PsA with peripheral polyarthritis involvement. However, it has been observed that despite more than half of the patients receiving csDMARD therapy, 47% of patients still developed bone erosion within the first two years. For patients with an inadequate response to csDMARDs, biologic disease-modifying antirheumatic drugs (bDMARDs) are recommended, such as TNF inhibitors, IL-17 blockers, IL-12/IL-23 antagonists, IL-23 antagonists, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), and tsDMARD treatments. However, most bDMARDs are injectable formulations, which are inconvenient to use, pose long-term safety and drug resistance issues, and surveys have found that most patients prefer oral treatments rather than intravenous infusion or injectable biologics. Reports indicate that the long-term treatment persistence of TNFi is only 24.8%-33.6%.

As a severe chronic disease, traditional treatment regimens for PsA have significant issues with efficacy and safety. Moreover, no biologics (e.g., TNFi, IL-17A, etc.) have been approved for the treatment of PsA in China. Given the current lack of alternative therapies, patients with PsA urgently need safe, convenient, and adherence-friendly treatments for long-term standardized management.

Tofacitinib's recent approval in China for the PsA indication is based on two global pivotal Phase III studies (A3921091 and A3921125) and one long-term extension study (A3921092) in PsA. In patients with inadequate response to csDMARDs who were TNFi-naïve, tofacitinib demonstrated efficacy comparable to TNFi, and it also achieved the primary efficacy endpoint in TNFi-IR populations. As an oral JAK inhibitor, tofacitinib holds promise in addressing the currently unmet medical needs of PsA patients12,13,14. Xeljanz® (tofacitinib citrate), the world’s first approved oral targeted small molecule drug for PsA treatment, blocks the JAK-STAT pathway and inhibits various cytokines associated with PsA. It is effective for multiple symptoms such as joint swelling and pain, skin lesions, enthesitis, dactylitis, etc., as well as for patients with inflammation-related comorbidities (e.g., IBD). Unlike biologics, Xeljanz® is administered orally, significantly improving patient adherence to treatment and promoting the sustainability of long-term therapy12,13,14.

Currently, Xeljanz® (tofacitinib citrate tablets) has been approved for the treatment of PsA in more than 80 countries and regions, including China, the United States, and the European Union. Tofacitinib citrate extended-release tablets have been approved for the treatment of PsA in more than 20 countries and regions, including China, the United States, and the European Union.

References:

1.Gladman DD, Antoni C, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii14 17.

2.McHugh NJ. Traditional schemes for treatment of psoriatic arthritis. J Rheumatol. Suppl. 2009 Aug; 83:49 51.

3. Chinese Rheumatology Association. Guidelines for the Diagnosis and Treatment of Psoriatic Arthritis. Chin J Rheumatol, 2010 Sep; 149(9): 613-633

4.Leung YY, Tam LS, Kun EW, et al. Impact of illness and variables associated with functional impairment in Chinese patients with psoriatic arthritis. Clin Exp Rheumatol. 2008 Sep Oct; 26(5):820-6

5.Zhu TY, Tam LS, Leung YY, et al. Socioeconomic burden of psoriatic arthritis in Hong Kong: direct and indirect costs and the influence of disease pattern. J Rheumatol. 2010 Jun;37(6):1214-20

6.Yue T, et al. Comparison of Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in Evaluating Anxiety and Depression in Patients with Psoriatic Arthritis. Dermatology. 2020;236(2):170-178

7.European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Gossec L, et al. Ann Rheum Dis 2015;0:1–12

8.Kane D, Stafford L, Bresnihan B, FitzGerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology (Oxford) 2003; 42: 1460-8

9.Barclay N, Tarallo M, Hendrikx T, et al. Patient Preference for Oral Versus Injectable and Intravenous Methods of Treatment for Rheumatoid Arthritis. Value in Health 2013;16:A568

10. Buckley C, Cavill C, Taylor G, et al. Mortality in psoriatic arthritis — a singlecenter study from the UK. J Rheumatol 2010; 37: 2141-4.

11. Tymms K. et al. Treatment patterns among patients with rheumatic disease (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated arthritis (UnA)) treated with subcutaneous TNF inhibitors. Clin Rheumatol. 2018 Jun;37(6):1617-1623.

12. N Engl J Med 2017; 377:1537-1550, DOI: 10.1056/NEJMoa161597.

13. N Engl J Med 2017; 377:1525-1536, DOI: 10.1056/NEJMoa1615977,

14. Rheumatol Ther. 2020 Sep;7(3):553-580. doi: 10.1007/s40744-020-00209-4. 

15. Michelsen B, Fiane R, Diamantopoulos AP, et al. A comparison of disease burden in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. PLoS One 2015; 10(4): 0123582.

16. Kotsis K, Voulgari PV, Tsifetaki N, et al. Anxiety and depressive symptoms and illness perceptions in psoriatic arthritis and associations with physical health-related quality of life. Arthritis Care Res (Hoboken) 2012; 64: 1593-601.

17. Tillett W, Shaddick G, Askari A, et al. Factors influencing work disability in psoriatic arthritis: first results from a large UK multicentre study. Rheumatology (Oxford) 2015; 54: 157-62.

18. Arumugam R, McHugh NJ. Mortality and causes of death in psoriatic arthritis. J Rheumatol Suppl 2012; 89: 32-5.

Editor: Dadasiva

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