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

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

Rheumatoid Arthritis
(RA) is one of the most debilitating chronic autoimmune affecting joints
leading to inflammation, pain, persistent synovitis, and eventual joint
destruction. RA primarily affects small joints and may have extra-articular
involvement in organs such as the lungs, heart etc. Prima facie, this disease
causes severe disability, decreased quality of life and life expectancy. RA
disease progression leads to bone erosion and deformities limiting the
patient’s daily activities. RA is a chronic disease associated with high
healthcare utilisation (direct costs) and productivity loss (indirect costs) in
adults. [1,2]

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,

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.


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.

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.

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

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