|Year : 2016 | Volume
| Issue : 1 | Page : 33-37
Prescription pattern in patients with rheumatoid arthritis in a teaching tertiary care hospital
Akhil Dahiya, Bhupinder Singh Kalra, Anmol Saini, Uma Tekur
Department of Pharmacology, Maulana Azad Medical College, New Delhi, India
|Date of Web Publication||25-Jan-2016|
Bhupinder Singh Kalra
Department of Pharmacology, Maulana Azad Medical College, New Delhi
Source of Support: None, Conflict of Interest: None
Objective: This study was conducted, with the aim to analyze the pattern of use of antirheumatic drugs in a Tertiary Care Hospital in Delhi, India. Methodology: The study was carried out in 150 patients who were on treatment with antirheumatic drugs at least for the past 6 months. Patient demographic details, duration of illness, comorbid conditions, drugs prescribed, adverse drug reactions (ADRs), and usage of complementary and alternative medicine (CAM) were used to analyze the pattern of drug use. Results: In our study, we observed that in patients with rheumatoid arthritis (RA), the most commonly prescribed disease-modifying antirheumatic drugs (DMARD) was methotrexate followed by hydroxychloroquine and sulfasalazine. DMARD combination with 3 drugs (59.3%) was the most common regimen followed by DMARD combination with 2 drugs (32.6%). Polypharmacy was seen in most of the prescriptions, but 76.3% of the drugs were from Essential Medicine List of Government of National Capital Territory, Delhi. About 40.7% of the prescriptions were prescribed by generic names. CAM was used by 13.3% of the study patients. Conclusion: The drug use pattern in RA was found to be DMARDs dependent. The concomitant use of three DMARDs was the preferred therapy. Biologics were not being used although indicated as per guidelines. ADRs associated with RA treatment were generally mild in severity and involved gastrointestinal tract.
Keywords: Drug utilization, prescription pattern, rheumatoid arthritis
|How to cite this article:|
Dahiya A, Kalra BS, Saini A, Tekur U. Prescription pattern in patients with rheumatoid arthritis in a teaching tertiary care hospital. MAMC J Med Sci 2016;2:33-7
|How to cite this URL:|
Dahiya A, Kalra BS, Saini A, Tekur U. Prescription pattern in patients with rheumatoid arthritis in a teaching tertiary care hospital. MAMC J Med Sci [serial online] 2016 [cited 2020 Apr 2];2:33-7. Available from: http://www.mamcjms.in/text.asp?2016/2/1/33/174835
| Introduction|| |
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that may lead to erosion of cartilage and bone. Uncontrolled RA is associated with joint deformity and significant health care related expenses. RA affects approximately 1% of adult population globally. The prevalence of RA in the adult population in India is approximately 0.75%.
Disease-modifying antirheumatic drugs (DMARDs) control disease activity, reduce joint erosions and improve quality of life of patients in RA. The 2012 American College of Rheumatology guidelines for the treatment of RA advocates early initiation and aggressive use of DMARDs in patients with RA. These guidelines recommend the initiation of DMARDs in early RA of <6 months duration as monotherapy for patients with low disease activity and as combination therapy for moderate- or high-disease activity. Biologics should be the initial choice of drugs in persons with high RA activity and poor prognostic factors. The use of DMARDs and other drugs for RA are associated with number of adverse drug reactions (ADRs) such as gastritis, leucopenia, hepatotoxicity, stomatitis, pruritus, and thrombocytopenia. Earlier studies have shown that most monitored ADRs requiring discontinuation were seen early in therapy, with median time of onset of <6 months., The data on the incidence of ADRs of these drugs in Indian setting are very limited. Prashker and Meenan observed that the cost of monitoring and treating side effects contributed to over 60% of the total cost of all drugs in RA. A study in Mumbai concluded that cost of drugs such as antisecretory agents, calcium supplements, and bisphosphonates which were given for the treatment or prevention of ADRs increased the total cost of RA therapy. Hence, cost is an important consideration in the management of RA.
Complementary and alternative medicine (CAM) is frequently used by patients with RA both in western countries as well as in developing countries such as India. It has also been reported that patients using CAM are likely to withhold the use of CAM from their treating physicians. In addition, the ADRs and drug-drug interactions with CAM and the mainstream medicines remain largely unknown.
There is a paucity of data on ADRs associated with antirheumatic drugs in the Indian population. The prescribing trends and the economics of RA treatment are largely unknown. Hence, this study was planned to assess the current prescribing trends in RA treatment, the ADRs associated with the treatment, and the concomitant usage of CAM.
| Methodology|| |
This prospective observational study was conducted in RA Clinic of Lok Nayak Hospital, New Delhi, after the approval of the Institutional Ethics Committee. The study was conducted over a period of 1 year between June 2014 and June 2015. A total of 150 patients were enroled in the study as per the inclusion criteria. Written and verbal informed consent was taken from all the patients. Patients were diagnosed and treated by senior residents.
The inclusion criteria that were followed:
- Diagnosed patients with RA of either sex
- On treatment for at least 6 months with minimum of 2 contact periods
- Adult patients willing to give informed consent.
The exclusion criteria that were followed:
- Patients requiring hospitalization
- Patients with neurobehavioral disorder or psychiatric illness.
Following details were recorded from each prescription: (1) Patient's demographic details; (2) details about patient's disease; (3) concomitant illness; and (4) treatment details.
To study the prescription pattern, following prescribing indicators were used: (1) Percentage (%) of drugs prescribed by generic name; (2) average number of drugs per encounter; (3) percentage of drugs with injections prescribed; (4) average drug cost per contact; (5) percentage (%) of drugs prescribed from the Essential Medicines List of Government of National Capital Territory (NCT) of Delhi.
ADRs were recorded using the Central Drugs Standard Control Organization ADR performa. The outcome parameters were (1) types of ADRs; (2) incidence of each ADR; (3) symptomatic treatment required for ADR; (4) requirement of de-challenge; (5) whether re-challenge was performed, if ethically allowed. Causality assessment for the ADRs was performed as per the WHO causality assessment Uppsala Monitoring Centre (UMC) Scale. ADRs were graded as mild, moderate, severe, and severe life-threatening as follows: (1) Mild - transient or mild discomfort; no limitation in activity; no medical intervention/therapy required. (2) Moderate - limitation in physical activity; some assistance may be needed for normal activity; no or minimal medical intervention/therapy required. (3) Severe - marked limitation in physical activity; some assistance usually required; medical intervention/therapy required, hospitalization possible. (4) Severe life-threatening - extreme limitation in physical activity; significant assistance required; significant medical intervention/therapy required, hospitalization necessary.
The usage of CAM was assessed. Patients were asked about the type and duration of CAM usage.
| Results|| |
One hundred fifty patients with a diagnosis of RA were enroled in the study. Among the 150 patients, 115 (76.7%) were females and 35 (23.3%) were males. The mean age was 43.6 years. The demographic details and disease-related information have been represented in [Table 1] and [Table 2], respectively.
In our study, the average number of drugs per prescription was 8.06. Approximately 41% of drugs were prescribed by their generic name [Table 3]. Approximately 76.3% drugs were prescribed from the Essential Medicine List 2013, Government of NCT of Delhi. Only 5 prescriptions (3.3%) contained injectable drugs.
Among the drugs prescribed for RA, DMARDs comprised 35.4% of all the drugs [Table 4]. Nonsteroidal anti-inflammatory drugs constituted 13.7% of all the drugs prescribed. Corticosteroids constituted 4.02% of all the drugs prescribed. No drug was prescribed from the class of biologics [Figure 1].
|Figure 1: Classes of drugs prescribed. DMARDs: Disease-modifying antirheumatic drugs, NSAIDs: Nonsteroidal anti.-inflammatory drugs|
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Monotherapy was prescribed in only 3 prescriptions; rest all (98%) received combination therapy. Majority of the prescriptions (95.3%) contained DMARDs. Eighty-nine prescriptions (59.3%) comprised DMARDs with 3 drugs. Forty-nine prescriptions had DMARDs with 2 drugs. Five prescriptions had only one DMARD. Among the DMARDs, methotrexate was present in 136 prescriptions (90.7%). Hydroxychloroquine was present in 132 prescriptions (88%). Sulfasalazine was prescribed in 100 prescriptions (66.7%).
Various combinations of drug classes were used [Figure 2]. The combinations used have been summarized in [Table 5].
|Figure 2: Various combinations of drug classes used. DMARDs: Disease-modifying antirheumatic drugs, NSAIDs: Nonsteroidal anti-inflammatory drugs|
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Adverse drug reactions
ADRs were reported in 77 (51.3%) of patients. The most common ADR was nausea and vomiting (29.3%) followed by epigastric pain (21%). The other common side effect included headache and constipation [Table 6].
Symptomatic treatment was required in five patients. During our study, no patient was hospitalized due to an ADR. In two cases, drugs were discontinued due to a suspected ADR. The first case was with methotrexate; the patient developed derangement in liver function test. The second case was with hydroxychloroquine; the patient developed vision problems. No rechallenge was performed in either of these cases.
In terms of severity, majority (81%) of the ADRs were mild. Five ADRs were moderate. The causality assessment was carried out according to the WHO-UMC causality assessment scale. This assessment revealed that ADRs in two patients were “Probable.” In 59 patients, the ADRs were “Possible.” In 16 patients, the ADRs were “Unlikely.”
Complementary and alternative medicine usage
In our study, we observed that CAM was used by 20 patients (13.3%). Thirteen patients used Ayurveda; three patients used Unani System of Medicine [Table 7]. Two patients used Homeopathy system, whereas two patients used both Homeopathy and Ayurveda. Majority of these patients were using CAM since last 1 year and reported no benefit. None of these patients reported or recalled any ADR while on CAM therapy.
| Discussion|| |
The findings of the prescription pattern study conducted in a Tertiary Care Hospital, Delhi, provide information about the demographic data, prescribing patterns, and ADRs. Majority of the patients were females, and the age of onset was middle age. RA is one of the many chronic inflammatory diseases that predominate in females. The prevalence is about 2.5 times higher in females than males. Our study showed a considerable female predominance of RA, i.e., 77%. A recent study conducted by Mittal et al. in India has reported that more than 80% of the RA patients were females, in agreement with our study. Another study conducted in India has shown that female patients constituted 83.46% of the sample population; 32% patients had other comorbid conditions. This finding is also in line with the other studies.
In our study, the average number of drugs per prescription was found to be 8.1, which is more than the WHO recommendations. It has been recommended that the limit of number of drugs prescribed per prescription should be two and that justification for prescribing more than two drugs would be required because of the increased risk of drug interactions. The increase in the number of drugs per se also increases the cost of prescription and patients may not purchase or take the prescribed drugs. This nonadherence to the therapy can deteriorate the said condition, prolonging the treatment duration. The present study observed that only 41% drugs were prescribed by their generic name. However, approximately 76% of the drugs were prescribed from the Essential Medicine List, NCT of Delhi. This is a relatively higher number.
Methotrexate was the DMARD of choice by the prescribing physician. Approximately 60% patients were on DMARDs with 3 drugs. These included methotrexate, sulfasalazine, and hydroxychloroquine. In the study conducted in Mumbai, it was seen that DMARDs with 2 drugs were commonly preferred. Another study by Sukhpreet et al. also found that combination of 2 DMARDs was commonly prescribed. Study by Shini et al. reported that majority of the patients were on single DMARD. The variation in number of DMARDs prescribed might be due to the varied severity of disease encountered in different hospital settings. Calcium supplements and gastroprotective agents were also present in a significant number of prescriptions. These were probably given to prevent drugs ADRs such as epigastric pain and steroid-associated osteoporosis. Folic acid was added to prevent methotrexate associated anemia. ADRs were reported from a significant number of patients (51%). However, majority of the ADRs were mild in nature and did not require any minor intervention.
Biological agents (non-tumor necrosis factor [TNF] and anti-TNF) approved for treatment of RA were neither prescribed nor administered to patients. Drugs such as abatacept, rituximab, etanercept, and adalimumab are not included in essential drug list; as a result, these drugs are not available for patients free of cost and are not being prescribed too for the same reason.
The usage of CAM was relatively low in the study population. None of the patients reported any benefit from the usage of CAM. However, no ADRs were recorded from the use of these systems of medicine.
| Conclusions|| |
The drug use pattern in RA was found to be primarily based on DMARDs. The concomitant use of three DMARDs was the preferred therapy. ADRs reported were generally mild in severity. Significant fraction of drugs prescribed was for prevention of ADRs. CAM usage was relatively low in the study population. Usage of biological agents for the treatment of RA should be undertaken as evidence shows them to be effective with minimal adverse effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wong JB, Ramey DR, Singh G. Long-term morbidity, mortality, and economics of rheumatoid arthritis. Arthritis Rheum 2001;44:2746-9.
Kvien TK. Epidemiology and burden of illness of rheumatoid arthritis. Pharmacoeconomics 2004;22 2 Suppl 1:1-12.
Mijiyawa M. Epidemiology and semiology of rheumatoid arthritis in third world countries. Rev Rhum Engl Ed 1995;62:121-6.
Choi HK, Hernán MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: A prospective study. Lancet 2002;359:1173-7.
Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al
.2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64:625-39.
Mody GM, Cardiel MH. Challenges in the management of rheumatoid arthritis in developing countries. Best Pract Res Clin Rheumatol 2008;22:621-41.
Bernatsky S, Ehrmann Feldman D. Discontinuation of methotrexate therapy in older patients with newly diagnosed rheumatoid arthritis: Analysis of administrative health databases in Québec, Canada. Drugs Aging 2008;25:879-84.
Alarcón GS, Tracy IC, Strand GM, Singh K, Macaluso M. Survival and drug discontinuation analyses in a large cohort of methotrexate treated rheumatoid arthritis patients. Ann Rheum Dis 1995;54:708-12.
Prashker MJ, Meenan RF. The total costs of drug therapy for rheumatoid arthritis. A model based on costs of drug, monitoring, and toxicity. Arthritis Rheum 1995;38:318-25.
Gawde S, Shetty Y, Merchant S, Kulkarni U. Drug utilization pattern and cost analysis in rheumatoid arthritis patients – A cross-sectional study in tertiary care hospital, Mumbai. Br J Pharm Res 2013;3:37-45.
Ramos-Remus C, Raut A. Complementary and alternative practices in rheumatology. Best Pract Res Clin Rheumatol 2008;22:741-57.
Mittal N, Mittal R, Sharma A, Jose V, Wanchu A, Singh S. Treatment failure with disease-modifying antirheumatic drugs in rheumatoid arthritis patients. Singapore Med J 2012;53:532-6.
Shini VK, Aboobacker S, Pahuja S, Revikumar KG, Bhasi R. Pharmacoeconomic study of DMARDs in the management of rheumatoid arthritis. Int J Pharm Sci Rev Res 2010;5:148-54.
Sukhpreet, Agarwal V, Tiwari P. Treatment and monitoring costs in rheumatoid arthritis: Preliminary results from an Indian setting. Indian J Pharm Sci 2007;69:226-31.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]