|Year : 2019 | Volume
| Issue : 1 | Page : 7-8
Advanced therapies for inflammatory rheumatic diseases in resource-poor settings
Department of Medicine and Laboratory Medicine and Pathobiology, University of Toronto; Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, University Health Network, Toronto, Ontario; Department of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada
|Date of Web Publication||14-Mar-2019|
Dr. Vinod Chandran
Toronto Western Hospital, 1E 416, 399 Bathurst Street, Toronto M5T 2S8, Ontario
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Chandran V. Advanced therapies for inflammatory rheumatic diseases in resource-poor settings. Indian J Rheumatol 2019;14:7-8
Targeted biological and synthetic disease-modifying antirheumatic drugs (DMARDs) have revolutionized the management of autoimmune inflammatory rheumatic diseases. The first proof-of-principle clinical trial of a biologic, initially with ten patients, was conducted in 1992 using infliximab (then called cA2) in severe rheumatoid arthritis (RA) by Feldman and Maini and was an example of effective academia–industry collaboration. Since then, several biologicals and more recently small molecules targeting specific molecules and pathways have been approved for the management of inflammatory rheumatic diseases including RA, axial spondyloarthritis (SpA), psoriatic arthritis, systemic lupus erythematosus, vasculitis, and juvenile idiopathic arthritis.
Although more effective than traditional agents for the management of these diseases, safety and cost have been the two main concerns while recommending treatment with these agents. The advent of biosimilars has led to lower cost of treatment; the cost remains a significant barrier for access to these medications for most patients worldwide. Although clinical trials have demonstrated that these drugs are largely safe, infections, malignancies, and autoimmune adverse events remain of concern. The safety when using these drugs in patients seen in routine practice, i.e., in those with comorbidities that would exclude them from inclusion in clinical trials, is of concern. Therefore, registries have been established to complement information from randomized controlled trials with “real-world” evidence on the effectiveness and safety of the newer agents in the treatment of inflammatory diseases in specific regional population-based cohorts. Significant challenges to initiating and maintaining such registries include cost, clinical and administrative burden to the physician, and incomplete data capture, leading to methodological challenges in conducting studies with the data. In Europe, these registries are largely funded jointly by pharmaceutical companies, with the conduct, analysis, and publications being done independently by academics. The government mandates support for such registries because it funds treatment for all patients receiving these medications through national health-care systems.
There are regional variations in the use of biologics. In the Indian context, the need to manage patients in a cost-constrained setting, lack of uniform and adequate government or private insurance funding for healthcare, and high prevalence of infections especially tuberculosis have led to “innovative” strategies to minimize the use of biologics and targeted small-molecule inhibitors. However, there are few published reports on the clinical experience including response, drug survival, and adverse events in the management of immune-mediated inflammatory diseases using the newer therapies. In this issue of the Indian Journal of Rheumatology, Shobha et al. report the prescribing patterns and safety of the use of biologics in immune-mediated rheumatic diseases in patients registered in the Karnataka Biologics Cohort. This article and related publications from this cohort is a welcome addition to the literature on the use of these agents in resource-poor settings.,
The authors aimed to describe the prescription patterns, infections, and their relationship with the drugs prescribed in a multicentric study in Karnataka, India, organized by the Karnataka Rheumatology Association. The most common indication for treatment with biologics was SpA and not RA as reported from cohorts elsewhere, the reasons of which are unclear. Although there was a high prevalence of latent tuberculosis, treatment prevented overt tuberculosis because no patient developed tuberculosis after receiving prophylactic treatment with isoniazid and rifampicin. However, ten patients (4.1%) developed tuberculosis within the time period of the study, none of whom had screened positive for latent tuberculosis. This could indicate the failure of screening or de novo exposure and infection. Significantly, there were four deaths, which is a high number within this short time period; one from disseminated tuberculosis and one from sepsis (two cause not reported). Almost a third of the patients used reduced dosage or frequency of drugs and more than 10% stopped treatment following significant improvement.
There are, however, many drawbacks to the study which have been recognized by the authors. The results indicate many differences in the prescribing practice, treatment regimen, and adverse events in India compared to registries elsewhere. For better understanding of the disease course, treatment, and prognosis, I would suggest that the Indian Rheumatology Association set up prospective registries of all major disease groups irrespective of treatment to better understand prescribing practices, effectiveness, and safety. These multi-centre cohorts could also be used to conduct pragmatic clinical trials with DMARDs, lower doses of biologics, and combination of DMARDs and biologics, perhaps at a lower dose, as well as biosimilars. Funding and administrative burden would be significant challenges that would, however, need to be overcome. With support from the government, philanthropic organizations, academic institutions, and pharmaceutical industry with unrestricted grants, such an initiative would greatly benefit millions of patients suffering from inflammatory rheumatic diseases in India and inform clinical practice not only in India, but also in other resource-constrained settings.
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