|Ahead of print publication
Prescribing patterns and safety of biologics in immune-mediated rheumatic diseases: Karnataka biologics cohort study group experience
Vineeta Shobha1, Vijay Rao2, Anu Mohan Desai1, Ramesh Jois3, Chandrashekara Srikantiah4, BG Dharmanand5, Sharath Kumar6, Pradeep Kumar7, Chethana Dharmapalaiah7, KM Mahendranath8, Shiva Prasad9, Manisha Daware10, Yogesh Singh2, Uma Karjigi3
1 Department of Clinical Immunology and Rheumatology, St. John's Medical College Hospital, Bengaluru, Karnataka, India
2 Department of Rheumatology, Manipal Hospital, Bengaluru, Karnataka, India
3 Department of Rheumatology, Fortis Hospital, Bengaluru, Karnataka, India
4 Chanre Rheumatology and Immunology Research Centre, Bengaluru, Karnataka, India
5 Department of Rheumatology, Sakra Hospital, Bengaluru, Karnataka, India
6 Department of Rheumatology, Columbia Asia Hospital, Bengaluru, Karnataka, India
7 Department of Rheumatology, Apollo Hospital, Bengaluru, Karnataka, India
8 Samarpan Health Centre, Bengaluru, Karnataka, India
9 Department of Rheumatology, Vikram Hospital and Heart Care, Mysore, Karnataka, India
10 Department of Rheumatology, Narayana Hrudalaya, Bengaluru, Karnataka, India
St. John's Medical College and Hospital, Sarjapur Road, Bengaluru - 560 034, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Biologics are widely used in Autoimmune rheumatologic diseases (AIRDs), however the need to capture real life data which monitors indications, adverse reactions cannot be over emphasized.
Methods: This is a cross-sectional ambidirectional multi-center study conducted over 8 months from January 2016 to August 2016, across 12 tertiary care rheumatology centers in Karnataka, India conducted by members of the Karnataka Rheumatology Association.
Results: The most common biologic prescribed is tumour necrosis factor antagonist etanercept. Commonest indication for biologics being Spondyloarthropathy group of disorders. The most common cause for stopping biologics is clinical improvement. Only 4.8% of patents discontinued biologics due to ADRs.
Conclusion: The prescribing patterns, mode of use, prebiologics screening methods, and adverse event profile are similar across centres. Pre-screening for latent tuberculosis (TB) is consistent across centres, and TB prophylaxis appears to be effective in preventing its reactivation.
Keywords: Autoimmune, biologics, India, Karnataka biologics cohort, Karnataka, rheumatic diseases
|How to cite this URL:|
Shobha V, Rao V, Desai AM, Jois R, Srikantiah C, Dharmanand B G, Kumar S, Kumar P, Dharmapalaiah C, Mahendranath K M, Prasad S, Daware M, Singh Y, Karjigi U. Prescribing patterns and safety of biologics in immune-mediated rheumatic diseases: Karnataka biologics cohort study group experience. Indian J Rheumatol [Epub ahead of print] [cited 2019 Jan 18]. Available from: http://www.indianjrheumatol.com/preprintarticle.asp?id=248775
| Introduction|| |
Autoimmune rheumatologic diseases (AIRDs) afflict approximately 1% of Indian population. Mainstay of the treatment of AIRDs is conventional synthetic disease-modifying antirheumatic drugs. Biologic response modifiers or simply termed biologics are recommended in specific recommended circumstances while treating AIRDs., In the Indian market, both biologics as well as biosimilars are available, but at a substantially high cost. Therefore, biologics are utilized infrequently and that too for short term, with an intention to push for decent disease control rather than aiming for good disease control.
Biologics have stood the test of time nearing two decades, but there is a lack of formal data collection which systematically captures prescribing pattern and choice in real-life clinical practice. Rheumatologists across Karnataka state, India, pooled together information on prescribing patterns and adverse events encountered during biologics use in day-to-day clinical practice. The current study is first of its kind approach that methodically captures this information and attempts to highlight the usage and safety profile of both biologics and biosimilars in real-life clinical practice.
The objectives of our this study were – (1) to describe prescription patterns of patients who receive biologics and biosimilars, (2) to delineate the frequency and types of infections in biologic-experienced patients, and (3) to study the relationship between various biologic response modifiers and types of infections encountered.
| Methods|| |
This is a cross-sectional ambidirectional multicenter study conducted over 8 months from January 2016 to August 2016, across 12 tertiary care rheumatology centers in Karnataka, India, using a comprehensive prestructured pro forma. This study is organized by Karnataka rheumatology association. Patients suffering from rheumatoid arthritis (RA), spondyloarthropathies such as ankylosing spondylitis, psoriatic arthritis (PsA), systemic lupus erythematosus, vasculitis, and other autoimmune diseases are typically treated with a combination of conventional disease-modifying antirheumatic drugs (DMARDs) as the first line of management. Patients with aggressive disease, who have poor relief or intolerance to DMARDs/immunosuppressants, are advocated biologic therapy (tumor necrosis factor [TNF] blockers, interleukin-6 antagonists, abatacept, rituximab, and their biosimilars). Patients older than 18 years who received ≥1 dose of biologic/biosimilar were included in this study. Their baseline characteristics, prescribing pattern, baseline prebiologics screen, duration of prescription, and adverse effects were examined. Their data were retrieved from hospital records and by direct questioning of patients. A subgroup of 272 subjects was extracted from main study and analyzed separately for infections and tuberculosis.
This study was approved by the ethics committees of respective institutes. Informed written consent was obtained from all patients prior to their enrollment in this study.
| Results|| |
During the study, information was collated from 411 biologics-experienced patients. Comprehensive results of adverse events and infections such as TB were also collated (objective 3) and being published separately. [Table 1] describes their overall characteristics. Their disease indications and biologics/biosimilars used are described in [Table 2] and [Table 3], respectively. The most common disease indication for biologics use was ankylosing spondylitis, and the most common biologics group used was TNF blockers, with the most frequently used being etanercept and its biosimilar. 82/411 (19.9%) were using concomitant steroids at the time of data collection, 150/411 (36.4%) patients were using one or more DMARDs/immunosuppressants, and methotrexate was being coprescribed in 116/411 (28.2%).
All patients underwent screening for latent TB, which included tuberculin test or TB QuantiFERON or both. A chest X-ray was performed in all patients; high-resolution computed tomography chest was performed if there was high index of suspicion of pulmonary TB (n = 37). Screening investigations are depicted in [Figure 1]. Based on the screening tests, latent TB infection (LTBI) was diagnosed in 35 patients. All of them were treated with prophylactic antituberculous therapy and then subsequently treated with biologics.
During biologics/biosimilars treatment, ten patients (4.1%) suffered TB at varying time intervals. All of them had tested negative for Mantoux (10) and or interferon-gamma release assay (7). The pattern of TB included pulmonary/extrapulmonary/disseminated (3/3/4). Importantly, none of the patients who were administered prophylactic anti-TB treatment (ATT) developed TB postexposure to biologics. Eight of these ten TB patients responded well to ATT, one patient developed meningeal TB on treatment which responded to six-drug regimen of ATT, and one patient succumbed to disseminated TB.
The risk for TB infection was higher in those administered infliximab, concomitant steroids, DMARDs (two or more), female sex, non-RA indication for biologic use and those with coexisting medical conditions. Patients treated with etanercept had least incidence of TB. None of the patients treated with rituximab or tocilizumab developed TB. For an average use of biologics for 11.64 months/per patient, for 411 patients, this is a fairly a small number, considering approximately 40% prevalence of LTBI in India.
Adverse drug reactions (ADRs) were noted in 68 (16.5%) of biologics experienced patients. They were mild-moderate in 42 (10.2%) patients, while serious adverse events were noted in 26 (6.3%). The most common mild-to-moderate adverse events included local site reactions, infusion reactions, and minor infections. Patients with coexistent medical illnesses, concomitant steroid use were more likely to experience adverse events (Supplementary online Tables) [Additional file 1].
It was noted that 31% of patients receive a lower dosage of biologic/biosimilar than the standard recommendation. The most common cause for stopping biologic/biosimilar is clinical improvement. Only 4.8% of patients stopped biologic/biosimilar due to ADRs.
| Discussion|| |
This is first kind of data from India demonstrating prescribing patterns, prebiologics workup, and adverse events including infections and TB encountered during its use. This study was not designed to study the efficacy of biologics. India is uniquely placed in terms of numerical burden of patients, economic considerations, availability of numerous biosimilar molecules, and rising patient expectations due to easy media access to information on recent medical advances.
The results of this study should be interpreted in light of some limitations. First, medical record abstraction might be subject to errors and/or omissions as these have been obtained from busy medical practice setups, predominantly private clinics and corporate hospitals. Second, interhospital differences, familiarity of rheumatologists with different biologics, ease of availability of biologics, and financial consequences widely contribute to treatment choices.
Structured registry data from many centers have shown that etanercept is one of the most commonly used biologics. Asian data from Hong Kong also document that etanercept is the most commonly used biologic for various indications. With respect to adverse events, no specific deviation from published literature was noted.
Most incidences of TB are typically related to infliximab use. Most patients across the world receive prebiologic TB prophylaxis for LTBI. Choice of antituberculous regimen is typically determined based on the prevalent sensitivity pattern. British registry reports that LTBI prophylaxis with isoniazid (INH) was administered for 768/2399 patients; in our study, 35/411 patients received INH and rifampin prophylaxis for LTBI. The risk factor for the development of TB in the current cohort has previously been detailed.
This study reconfirms the usefulness of prescreening methods in risk stratification of patients at greater risk for developing TB and efficacy of anti-TB prophylaxis regimens being used in everyday clinical practice. Maximum risk for developing TB was treatment with TNF inhibitors, especially infliximab, or its biosimilar. None of the patients who were administered prophylactic ATT developed TB postexposure to biologics.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]