|Ahead of print publication
Future of digital health and precision medicine in rheumatology practice in India
Joydeep Samanta1, Debashish Mishra2
1 Department of Rheumatology and Clinical immunology, Institute of Medical sciences and SUM hospital, Bhubaneswar, Odisha, India
2 Specialist Rheumatologist, Department of Rheumatology, Lifecare hospital, VPS healthcare, Abu Dhabi, UAE
|Date of Submission||18-Jun-2022|
|Date of Acceptance||20-Aug-2022|
|Date of Web Publication||20-Sep-2022|
Department of Rheumatology, Lifecare Hospital, VPS Healthcare, Near Village Mall, Musaffah, Abu Dhabi
Source of Support: None, Conflict of Interest: None
With the digitalization of the services across various sectors in an Indian setting, health care is also influenced by the same. It was evidenced during the COVID-19 pandemic that Indian patients were orienting themselves toward more teleconsultations and digital and smartphone-based health care. This not only saves time and money but also reduces the chances of hospital-acquired cross infections. This is more important for patients with rheumatic diseases who try to avoid frequent hospital visits despite the need for regular health-care consultations due to the aforementioned reasons. Apart from the telemedicine and smartphone apps, health care is expanding to robotics and artificial intelligence-based machine learning. Healthcare digitalization will lead to the expansion of precision based medicine. When more robust genomics, proteomics, metabolomics, and transcriptomics data become available for Indian patients with rheumatic diseases, management then would be more personalized than blanket therapy. However, such futuristic advancements face challenges of their own which are neither time nor knowledge bound. We are currently just at the tip of this massive iceberg. We describe various aspects of the future of digital health and precision medicine in rheumatology in an Indian setting.
Keywords: Digital rheumatology, health apps, India, omics, precision medicine, telemedicine
| Introduction|| |
Digitalization and precision in decision-making have not only embarked in the financial sector like unified payment interface, investment planning, or brokerage but also in the health-care industry. Gone are the days when Indians used to travel kilometers for a doctor visit, wait for days to get tested, or settle for the least available treatment. Indians are now in a better position to make informed decisions about their health. Rheumatology, in itself, is at an early phase of life, taking into consideration the factors such as the number of practicing rheumatologists (<1500; 209,000 patients with rheumatic complaints per rheumatologist), awareness about it among general people, the standard of rheumatology care available at primary/community health centers, early referral-based system to trained specialists, or best affordable therapeutics at all levels. The digital revolution that has taken shape during and post-coronavirus disease (COVID) times has at least outdone a few of these barriers. Digital health can be a blessing in disguise in the Indian scenario, provided its potential to benefit is explored without blindfolding to its infirmities.
Another trending concept in modern medicine is “Precision medicine.” It usually means tailoring therapeutic strategy on an individual basis. It is often used interchangeably with terms like “personalized medicine.” However, the personal approach to a patient, which is considered the cornerstone of precision medicine is being practiced for centuries and is not a novel thing. However, with the continuously expanding knowledge regarding diseases and their pathogenesis including pan-omics analysis like genomics, transcriptomics, metabolomics, and proteomics and therapeutic options, scopes of therapeutic individualization are also growing. Many argue that the term “personalized medicine” should better be replaced with the term “precision medicine.” However, to date, there is no well-accepted definition of precision medicine. As per the National Institute of Health, “precision medicine is an emerging approach for disease prevention and treatment that takes into account people's individual variation in genes, environment, and lifestyle.”
| Digital Health in Rheumatology|| |
Digital health is the use of telecommunication, virtual platforms, social media sites, or wearable devices for disease awareness, evaluation, monitoring, and treatment. Telemedicine, as a virtual platform, is not a novel concept, but its potential was realized during pan India COVID lockdown. Patients, primary care physicians or health-care providers, specialists, and experts could all be brought together at a given time point by virtual video calling apps. Images can be captured, analyzed, and recorded for future reference as well. This reduces travel costs and hospital bills, which can be utilized to fund medications and other assisted therapies.
Using tracker apps such as MyRA, PainScale, My Pain Diary, rheumatoid arthritis (RA) monitor, and Arthritis Tracker, patients are actively involved in assessing their disease activity and then consulting their physicians for therapy alterations. SMART-RA study by Syngle et al. showed that RA patients who monitored their disease activity via a mobile phone application had better disease control and quality of life compared to nonusers. Portals such as myRAteam or Wellness4U and social media sites such as Facebook, Twitter, and Instagram can connect patients with rheumatic diseases under a single community, and they can be group motivated for therapy compliance, physical rehabilitation, dietary modifications, positive reinforcements, social engagements to allay anxiety, and fear of unknown. They can, as well, create awareness (in vernacular languages too) about these undiagnosed diseases, their available therapies, and trained specialists to contact.
Physical rehabilitation and exercises form an essential part of rheumatological services. Patients who are unable to adhere to the same due to financial, traveling, or accessibility constraints can very well benefit from digital applications for physiotherapy (Virtual Health Coach) like Enhance Fitness and Workout For Arthritis or connect in real time to expert tutors via video calling apps. Ultimately, target is wholesome patient care which includes disease activity assessment, therapy modifications, physical rehabilitation, positive enforcements, regular follow-up, and a final goal of low disease activity with satisfying quality of life.
| Physician Support|| |
Does digitalization help physicians as well? Wearables like smartwatches that track daily activity and sleep patterns (subjectively) or apps like RheumaHelper and MdCal (objectively) help physicians to monitor disease activity., Artificial intelligence (AI)-based imaging reporting is targeted to minimize human errors and escalate clinical–radiological correlation. Various apps for disease activity assessments, drug dosing, and checking interactions help in daily clinical practice. Similarly digital updates on platforms such as Up-To-date, Medscape, and WebMd help to brush up on existing knowledge on any given topic and improvise medical decision-making abilities. Social media and digital platforms can facilitate distant education of young trainees in situations such as lockdown or another national crisis.,
Digital services such as Practo, Apollo 24/7, and 1MG have physicians who interact with distant patients, and the entire outpatient scenario is virtually created. The service providers arrange for home-based blood tests and medication delivery as well, which significantly cuts down on health-care costs. In 2019, the Government of India also launched eSanjeevani, an integrated platform for virtual consultations. Apart from patient consultation, even online surveys, research, registry formations, multicentric studies, and international collaborations can be done on various digital platforms. Maintenance of electronic health records on various clouds or data storage applications can help to retrieve previous clinical findings during patient follow-up, analyze data for study purposes, create evidence for modern medical practice, and propagate precision medicine-based practice.
| COVID-19 and Digital Health|| |
The biggest boost to digital health and teleconsultation was given during the COVID-19 national lockdown. Shenoy et al. have shown that the use of teleconsultation via WhatsApp during the COVID-19 pandemic helped almost 75% of patients with rheumatic diseases to continue medications safely. Similar findings were corroborated by Naveen et al. in myositis and Sandhu et al. in RA and showed patient satisfaction with teleconsultation services.
Due to the widespread use of telemedicine services, the Government of India formulated “Telemedicine Practice Guidelines” released on 25 March 2020. Furthermore, telemedicine departments are being created by the Government of India in various tertiary care centers for health-care delivery and capacity building in remote areas by a “hub and spoke model.” A “COVID-19 Global Rheumatology Alliance” registry was formed by digital crowdsourcing to collect information related to COVID-19 infection in patients with rheumatic diseases. Not only the teleservices but also the use of health tracker apps, AI-based robotic devices, and virtual health coaches saw a boost in use during the lockdown period.
| Precision Medicine in Rheumatology|| |
The idea of “Precision Medicine” is derived from oncology therapeutics like the use of trastuzumab for breast cancer patients expressing Her-2 receptor or tyrosine kinase inhibitor for lung cancer showing EGFR mutation. However, precision medicine in rheumatology is far more intricate due to the complex interplay of genetic and environmental factors. It may not be precise “Precision Medicine,” but personalized medicine is practiced in India where therapeutic decisions are made based on age, gender, comorbidities, fertility concerns, disease activity status, organs affected, seropositivity, and financial constraints. Better efficacy of rituximab in rheumatoid factor (RF) positive RA patients or relapsing ANCA associated vasculitis (AAV) patients, avoiding azathioprine in Thiopurine-methyltransferase (TPMT) or Nudix hydrolase 15 (NUDT 15) deficient patients 21 and better response to anti-tumor necrosis factor therapy in spondyloarthritis patients with active bone marrow edema on MRI23 are few examples where therapeutic decisions are taken based on personalized clinical, genetic or imaging information respectively. Similarly, prognostication of patients is feasible based on certain available knowledge like the titer of RF or anti-citrullinated peptide antibodies in RA, anti-proteinase 3, or myeloperoxidase positivity in AAV, or risk of scleroderma renal crisis in anti-polymerase III and anti-SCL-70-positive patients.
However, the question arises that how much “precision” is precise. With the rapidly developing pan-omics analysis, precision medicine has become far more complex and developed. Identification of various patient subgroups with the different pathophysiological processes with the help of molecular techniques has helped in tailoring treatment in different rheumatic diseases and thus has opened a new avenue in precision medicine. For example, molecular signatures in synovial tissue in RA patients have been shown to predict treatment response with myeloid gene signature in RA synovium associated with better response to TNF. Furthermore, in case of inadequate response to anti-TNF, synovial B-cell signature in RA patients can help in subsequent therapeutic decisions. Similarly in psoriatic arthritis, synovial T-cell phenotyping has been shown to predict treatment response to biological disease modifying anti-rheumatic drugs (DMARDs). A study in North Indian AAV patients showed an increased level of B-cell-activating factor (BAFF) in AAV patients compared to healthy control and thus indicating a potential role of anti-BAFF therapy in Indian AAV patients. In another study, a fall in urinary C3d level at 3 months in lupus nephritis after treatment initiation was found to be a predictor of good treatment response. These advances in transcriptomics and proteomics have helped to improvise the precision in clinical and therapeutic decision-making.
Singh et al. showed that the polymorphism in ATIC and ITPA genes was found to be predictors of methotrexate response in RA patients. One multicentric study in lupus nephritis patients had shown that the patients having CYP2C19*2 genetic variant are at increased risk of cyclophosphamide failure. Moreover, CYP2C19*2, CYP3A5*3, and GSTP1 genetic variants had a synergistic effect on cyclophosphamide failure. Recently, a multicentric study by Sharma et al. identified a monogenic type of polyarteritis nodosa patients with distinct clinical manifestation and good therapeutic response to anti-TNF therapy compared to other conventional immunosuppressants. These data from the genomic analysis have helped to further stratify and synchronize “precision” in clinical decision-making. Similarly, in the field of metabolomics, analysis of synovial fluid of reactive arthritis patients has shown synovial Phe/Tyr ratio being significantly higher compared to RA patients.
Despite more inroads in multi-omics analysis, due to the relative rarity of many rheumatic diseases, collecting an adequate amount of data for precision medicine can be difficult at times. This problem can be circumvented by the “machine learning” approach. In a given condition, from the available data, “machine learning” can stratify various patient subgroups by virtue of the “goodness-of-fit” model. Although still it is in infancy, with further research, “machine learning” can add another dimension to the field of precision medicine.
There are certain drawbacks of precision medicine too. Stratifications of various diseases based on multi-omics analysis are not always helpful. Like, despite lupus nephritis patients showing interferon (IFN) gene signature, anifrolumab (an anti-IFN therapy) was not successful in LN. Similarly, despite excessive BAFF production in AAV, belimumab, an anti-BAFF therapy failed in an initial study. Furthermore, many of these multi-omics analyses are very cumbersome and costly, thus making their application in a real-world setting very difficult.
However, even with all the limitations, one thing is obvious that the cornerstone of precision medicine is the knowledge of the pathophysiological and therapeutic aspects of various diseases. Hence, to make precision medicine a success, we need more data about various rheumatological diseases in an Indian setting. Indian Genome Variation database project, started in 2003, aims to provide data on reported and novel single nucleotide polymorphisms. “Genome India Project” started by the department of biotechnology in January 2020 aims to form a reference genome database. An Indian setting-specific proteomics database has been attempted under the flagship human protein reference database and other platforms such as Human Proteinpedia.
Limitations and challenges of digital health and precision medicine in India
Even though both the concepts of “Digital Health” and “Precision Medicine” [Figure 1] seem very futuristic and technology driven, there are multiple hurdles that need to be crossed. A few of the most obvious ones are highlighted below, along with their possible solutions [Table 1]. However, roadblocks are many on this untrodden and unknown path, which we will encounter as technology advances further.
|Figure 1: Various components of Digital Health and Precision medicine-based practice. At the interface of both these horizons a complete Digital-Precision based nation is possible|
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|Table 1: Various challenges and limitations of digital health and precision medicine in India with their relevant solutions|
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| Conclusion|| |
As India could digitalize nationwide unified payment services and make banking transactions hassle-free, similarly health-care digitalization is also possible. Once the health-care system gets digital and data are collected by linking to the UIN of every Indian citizen, precision medicine will also be quick to achieve. No doubt every habit formation and national project encounters challenges. Indians are now at a phase of accepting digitalization and personalized touch to every aspect of their life. Hence, the creation of a Digital-Precision based India could be a reality in near future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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