Decoding Safety and Efficacy of Generic Tofacitinib Tablets in Rheumatoid Arthritis: Indian Evidence

Managing Rheumatoid arthritis & Establishing Role of Targeted Synthetic DMARDs

The goal of treatment is to achieve remission or, if remission is not possible, to slow disease progression (low disease activity). Treatment modalities for RA include nonsteroidal anti-inflammatory medicines (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs), including conventional DMARDs (Methotrexate, Leflunomide, and Sulfasalazine), biologics DMARDs (Adalimumab, Etanercept, Infliximab, Rituximab, Tocilizumab) and targeted synthetic DMARDs (tsDMARDs) [Tofacitinib]. [1]

There’s a paradigm shift in the management of RA after the introduction of biologics DMARDs and tsDMARDs.[3] tsDMARDs such as Tofacitinib have been shown to reduce RA symptoms and improve quality of life. [1] According to European League Against Rheumatism (EULAR) guidelines, if the therapy targets are not met with the conventional DMARD strategy, a biologic DMARD or a tsDMARD such as Tofacitinib should be initiated. [4]

Tofacitinib is a Janus kinase (JAK) inhibitor that modulates immunological and inflammatory responses of cytokines - key players in the pathogenesis of RA. Tofacitinib is a reversible, competitive inhibitor that binds to the ATP-binding region in the catalytic cleft of the JAK kinase domain and inhibits JAK phosphorylation and activation, hence blocking STAT activation and gene transcription initiation in decreased cytokine production and immune response regulation. Tofacitinib offers a novel strategy for modifying immunological and inflammatory responses in patients with RA, which is especially relevant in individuals who do not respond to DMARDs or tumor necrosis factor inhibitors or who demonstrate a loss of responsiveness over time.[1]

Efficacy studies of Tofacitinib: Indian evidence [5]

There has been increased use of tofacitinib, in the Indian scenario, after its introduction. Phatak S et al. conducted a retrospective, single-centre analysis from Western India. The study was published in the Clinical Rheumatology journal (2022), reporting the safety and efficacy of Tofacitinib in treating 102 RA patients. The mean duration of therapy was 186 (74–505) days at evaluation. The study demonstrated a good response to generic tofacitinib treatment in Indian RA patients. Noteworthy parameters of the study include

• Significant reduction in simplified disease activity index (SDAI) from baseline among RA patients treated with Tofacitinib [ At onset (mean±SD) v/s at follow-up (mean±SD)-34.4±28.4 v/s 24.4±20.3, p=0.001]
• Significant reduction in C-reactive protein (CRP) from baseline in RA patients treated with Tofacitinib [At onset (mean±SD) v/s at follow-up (mean± SD)- 14.3±22.1 v/s 10.6±13.9 respectively, p=0.005]
• Disease activity score-28 (DAS28) was reduced among patients treated with Tofacitinib from baseline value [At onset (mean± SD) v/s at follow-up (mean± SD)- 4.79±1.54 v/s 4.27±1.4 respectively, p=0.002]
• Swollen joint count (SJC) reduction from its baseline value was observed in patients treated with Tofacitinib [At onset (mean± SD) v/s at follow-up (mean± SD)- 3.4±4.3 v/s 1.3 ± 2.3 respectively, p=0.000].
• Tender joint count (TJC) reduction was also seen in patients treated with Tofacitinib [At onset (mean± SD) v/s at follow-up (mean± SD)- 9 ± 7.8 v/s 5.2 ± 5.7 respectively, p=0.000].

The study did not report any major safety signals with Tofacitinib. No major serious adverse events (thrombosis, cardiovascular events, malignancies, mortality) were reported. Tuberculosis was reported in 4 patients. 13.75% of the patients suffered from minor side effects such as GI disorders, paraesthesia, rash, and itching. Considering the risk-benefit analysis, the benefits of tofacitinib outweigh the risk, justifying its rationale and for treating rheumatoid arthritis. In conclusion, tofacitinib showed excellent efficacy and a tolerable profile of adverse reactions in RA patients from India.

Takeaway Messages

Excruciating pain and reduced quality of life are among the most pressing concerns associated with rheumatoid arthritis. Several treatment options are available in the RA armamentarium. Tofacitinib provides an alternative option as an oral drug to the parenteral-administered biologic DMARDs. The safety and efficacy of tofacitinib have been demonstrated in several global studies. The introduction of targeted synthetic DMARDs like Tofacitinib has brought a new ray of light amongst RA patients.

References

1. Kawalec P, Śladowska K, Malinowska-Lipień I, Brzostek T, Kózka M. European perspective on the management of rheumatoid arthritis: clinical utility of tofacitinib. Ther Clin Risk Manag. 2017;14:15-29.

2. Bullock J, Rizvi SAA, Saleh AM, Ahmed SS, Do DP, Ansari RA, Ahmed J. Rheumatoid Arthritis: A Brief Overview of the Treatment. Med Princ Pract. 2018;27(6):501-507.

3. Tanaka Y. Recent progress in treatments of rheumatoid arthritis: an overview of developments in biologics and small molecules, and remaining unmet needs. Rheumatology (Oxford). 2021 Dec 24;60(Suppl 6):vi12-vi20.

4. Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023 ;82(1):3-18. Erratum in: Ann Rheum Dis. 2023;82(3):e76.

5. Phatak S, Khenat A, Malandkar M, Amin S. Real-world evidence of the effectiveness and safety of generic tofacitinib in rheumatoid arthritis patients: a retrospective, single-centre analysis from Western India. Clin Rheumatol. 2022 Oct;41(10):2961-2966.Decoding the Safety and efficacy of generic Tofacitinib tablets in Rheumatoid Arthritis: Indian Evidence