Abstract
Axial spondyloarthritis (axSpA), also known as ankylosing spondylitis (AS) is a chronic inflammatory condition affecting the spine and the sacroiliac joints. In India, with a prevalence ranging between 0.7 and 1.0 per 1,000 population, 1 the burden of axSpA is substantial. It mainly affects younger individuals before the age of 45 years. If treated inadequately, it results in severe impairment in the mobility of the spine and may even make the individuals handicapped. Effective treatment strategies are crucial to mitigate long-term complications, yet the availability and affordability of biologic therapies, which are considered the cornerstone in axSpA management, remain a challenge in resource-limited settings like India.
Assessment of the Spondyloarthritis International Society–European Alliance of Associations for Rheumatology (ASAS-EULAR) recommends nonsteroidal anti-inflammatory drugs (NSAIDs) as the first-line treatment and in case of insufficient response, biologic disease-modifying antirheumatic drugs (DMARDs), such as tumour necrosis factor (TNF) inhibitors and interleukin (IL)-17 inhibitors, or Janus kinase (JAK) inhibitors are suggested. 2
Although, the advent of biologics has transformed management strategies, yet disparities remain. In low-income countries like India, insurance coverage for advanced therapies is limited, and most patients bear the burden of out-of-pocket expenses for their medications. Even though very effective biosimilars have been available in India since 2014, many people still continue to struggle with the prices.
Tofacitinib, a targeted synthetic DMARD, inhibits JAK1 and JAK3 and hence inhibits production of inflammatory cytokines such as IL-17, IL-23 and many more. In 2012, the U.S. Food and Drug Administration approved it for the treatment of rheumatoid arthritis, but not for active axSpA until 2021. In November 2020, generic versions of tofacitinib were introduced in the Indian market, costing one-tenth of the monthly price of the innovator tofacitinib. Furthermore, in India, the monthly cost of generic tofacitinib is almost 10 times lower than the most economical adalimumab biosimilar. The convenience of oral administration, combined with the inexpensive cost of tofacitinib, has benefitted and enhanced the quality of life of patients who could not previously afford biologicals.
In this issue of the journal, a double-blind, placebo randomised controlled trial (RCT) by BV et al. 3 discusses the efficacy and safety of tofacitinib in 48 Indian AS patients. The authors have shown that over 12 weeks of trial, the tofacitinib group has shown significant improvement in disease activity scores ASAS20 and ASAS40. All secondary endpoints including disease activity and functional measures (BASDAI, ASDAS-CRP, BASMI and BASFI) and inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) also showed significant improvement. Patients on tofacitinib also showed a substantial decrease in serum TNF-α and IL-17A after 12 weeks. Previously, two placebo, RCTs, phase II and phase III by van der Heijde et al. 4 and Deodhar et al., 5 respectively, have shown similar results with tofacitinib in axSpA patients.
Another interesting study from India by Goswami et al. 6 has studied effectiveness and cost analysis of generic tofacitinib versus generic adalimumab in axSpA in real-world setting. In this study, the efficacy of tofacitinib was similar to that observed in previously conducted RCTs by van der Heijde et al. and Deodhar et al. Although retrospective data were compared to placebo-controlled data in this multicentric study, still, at 4 months, ASDAS low disease activity (LDA) was achieved in 47.9% versus 53.9% and 38.9%, respectively. These numbers are better than the placebo group but less than the adalimumab group. But, according to Goswami et al., at 6 months, the ASDAS LDA was comparable for the tofacitinib and adalimumab groups. Moreover, the cost of adalimumab per patient was about 10 times more than that of tofacitinib per patient.
The use of tofacitinib did not reveal any new safety signals, according to the Indian investigations by BV et al. and Goswami et al. Adverse metabolic consequences and total bouts of infections were rare and minor. Upper respiratory tract infections and diarrhoea were frequent side effects. The tofacitinib and placebo groups had similar infection rates. Herpes zoster, tuberculosis (TB), cytopenias, dyslipidaemia, thromboembolic events and significant cardiovascular events were not detected. The absence of cardiovascular events may be due to a younger patient group. India, being an endemic zone for TB, screening for latent TB before starting tofacitinib is a critical step. Similarly, due to immunosuppressive effects of tofacitinib on T-cells, reactivation of herpes zoster is always a risk and should be kept in mind. If possible, patients with age >50 years should be vaccinated with recombinant zoster vaccine prior to starting tofacitinib. But again, current cost of the vaccine is an issue in India.
The authors did well in presenting Indian data that shown good efficacy and safety with the usage of generic tofacitinib at a reasonable cost. There are avenues that could enhance the accessibility and affordability of tofacitinib in resource-limited settings. Local production of generic tofacitinib, which India has proven expertise in, could drastically reduce costs and make the medication more accessible to the general population. Additionally, initiatives by pharmaceutical companies, in collaboration with government health systems, could make tofacitinib more affordable, much like the model used for HIV and tuberculosis treatments.
Another crucial step is raising awareness about axSpA and its management. Early diagnosis, along with appropriate treatment protocols, can significantly reduce disease progression and improve patient outcomes. The role of medical societies and patient advocacy groups in educating both the public and healthcare providers cannot be overstated in this regard.
In conclusion, even if tofacitinib may give hope for better management of axSpA, the emphasis in India must continue to be on making sure that this optimism is translated into practical, reasonably priced treatment alternatives for the great majority of patients who live in environments with low resources.