INTRODUCTION:

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe disability and premature mortality.¹It is one of the most common autoimmune inflammatory arthritis in adults.²about 1% of the world population and approximately 0.75% of the adult Indian population is affected by RA.^3,4 RA significantly reduces patient health-related quality of life, progressive destruction of joint tissue leads to loss of body function, pain and fatigue.²which not only impacts the patient’s ability to perform daily activities but also increases mortality and exerts a heavy economic burden.^2,2Gradual onset of symmetrical arthralgia, synovitis of small joints of the hands, feet, and wrists, and morning stiffness are the characteristic features of RA.⁵ The primary goal of treatment of Rheumatoid arthritis should aim to reach clinical remission, to prevent structural damage and to provide improved quality of life in patients.⁵RA is regarded as a systemic illness because its^6,7 pathogenesis which affects internal organs, particularly heart, lungs, kidneys, blood vessels, brain.

The possibility of developing a serious infection is more in patients with RA. The pathobiology of the disease, the chronic comorbid conditions, as well as the sequelae of immunosuppressive treatment increases the susceptibility of RA patients to develop a serious infection. Evaluation of prescriptions and drug utilization studies help in the analysis of the recent trend of prescription patterns which will further help to identify the problems and provide feedback to prescribers.⁸Hence, this study aims to study the drug utilization pattern in rheumatoid arthritis.

MATERIALS AND METHODS:

Study Design, Duration and Site:

A retrospective study for six months in orthopaedics department of Justice K.S. Hegde Charitable Hospital: a tertiary care teaching hospital located in Dakshina Kannada district, Karnataka.

Inclusion and Exclusion Criteria:

Hospitalized patients in the orthopaedics department, presented from January 2013 to December 2017 of either sex. All Patients diagnosed with RA and were admitted at least once in the hospital were included in the study. Whereas patients treated in the outpatients department and patients with incomplete records were excluded from the study.

Sample Size:

The sample size required for this study was calculated as 400 patients. The sample size was arrived at taking into consideration the availability of patients during the study period at the study site.

Study Procedure:

Ethical approval from Institutional Ethics Committee was obtained before conducting the study (NGSMIPS/IEC/10/2018-19). A suitable data collection form was prepared to collect the details of patient demographics and prescription patterns. The relevant data of the patients who satisfy all inclusion criteria were collected to conduct the study. Details of inpatients diagnosed with rheumatoid arthritis such as complete patient demographic profile, diagnosis by the treating orthopedician and drug therapy details including drug name, a dose of the drug, route of administration, and duration of hospital stay were collected from the patient case records. In addition to that, relevant data on associated co-morbid conditions and infections with their management was also recorded from the medical records in a suitable data collection form. Qualitative characteristics were documented by using frequency/percentage and presented with suitable diagrams and graphs. Quantitative characteristics were presented with mean ± standard deviation. Data collected were entered in an excel spreadsheet and analyzed by using Statistical Package for Social Science. (SPSS-version 20.0)

RESULTS:

Demographic details of the study subjects:

A total of 400 inpatients diagnosed with Rheumatoid arthritis and treated for the same in the department of orthopaedics were included in the study. Among them, 317 (79.2%) were females, and 87 (20.8%) were males. The majority of the subjects belonged to the age group of 50-69years (48.9%). The age of the study population ranged from 18 - 89 years, with a mean value of 51.84 ± 18.842 standard deviations. The majority of the patients were admitted to the hospital for 1-7 days (26.5%). The number of drugs prescribed per encounter ranged from 1-20 with a mean value of 7 ± 2.77 standard deviations.

Drugs used in the management of Rheumatoid Arthritis:

Categories of drugs prescribed for the management of RA are summarised in Table 1.

Table 1: Categories of drugs prescribed for the management of RA.

Class of Drugs	No of Drugs
Class of Drugs	Frequency	Percentage (%)
DMARDS	600	39.2%
NSAIDS	340	22.2 %
Analgesics	386	25.2 %
Corticosteroids	205	13.4 %

Distribution of various DMARDs prescribed for the management of RA:

Out of the total 600 DMARDS prescribed to the patients, Methotrexate was the most prescribed drug (52.7%) followed by Hydroxychloroquine sulphate (42.5%) and Azathioprine (0.3%) was the least prescribed drug. DMARDS prescribed in RA patients are summarised in Table 2.

Various Corticosteroids prescribed for treatment of RA:

In this study, 205 Corticosteroids were prescribed to RA patients, out of which Deflazacort (46.8%) was the most prescribed drug, followed by Prednisolone (37.1%), and Hydrocortisone (3.9%) was the least prescribed corticosteroid. A detailed report of corticosteroids prescribed for the treatment of RA is summarized in Table 3.

Table 2: DMARDS prescribed in RA.

DMARDS	No of drugs
DMARDS	Frequency	Percentage
Methotrexate	316	52.7 %
Hydroxychloroquine sulphate	255	42.5 %
Sulfasalazine	17	2.8 %
Leflunomide	10	1.7 %
Azathioprine	2	0.3 %

Table 3: Corticosteroids prescribed in RA patients.

Corticosteroids	No of drugs
Corticosteroids	Frequency	Percentage
Prednisolone	76	37.1%
Methyl prednisolone	25	12.2 %
Deflazacort	96	46.8 %
Hydrocortisone	8	3.9 %

Various NSAIDs prescribed for treatment of RA:

A total of 340 NSAIDs were prescribed in the study population. The most commonly prescribed was Diclofenac (34.4%), followed by Indomethacin (27.6%). The least prescribed NSAID was found to be Etodolac (1.5%). A detailed report of the prescribed NSAIDs is summarized in Table 4.

Table 4: NSAIDS prescribed in RA patients.

NSAIDS	No of prescriptions
NSAIDS	Frequency	Percentage
Diclofenac	117	34.4 %
Aceclofenac	11	3.2 %
Etoricoxib	33	9.7 %
Indomethacin	94	27.6 %
Ibuprofen	12	3.5 %
Piroxicam	20	5.9 %
Etodolac	5	1.5 %
Naproxen	8	2.4 %
Flurbiprofen	24	7.1 %
Aspirin	16	4.7 %

Table 5: Comorbidities observed in RA patients

Co-morbidities		No of patients		Percentage %
		Male	Female	Percentage %
	Hypertension	14	56	21.1%
	Type II Diabetes Mellitus	16	46	18.7%
	Hypothyroidism	1	27	8.5%
	Anemia	15	85	30.2%
	Osteoarthritis	4	14	5.4 %
	IHD	4	12	4.8 %
	COPD	6	25	9.4%
	ILD	1	5	1.8%

Distribution of patients, according to co-morbidities observed:

Out of the total 400 RA patients included in the study, 331 patients were observed to have comorbidities. The Co-morbid diseases mostly identified were Anaemia, Hypertension, Type II Diabetes Mellitus, COPD, IHD, Hypothyroidism, Osteoarthritis, and Interstitial Lung Disease. The majority of the RA patients had Anemia as co-morbidity (30.8%) followed by Hypertension (21.1%). ILD (1.8%) was the least observed comorbidity. A detailed report on the comorbidities observed is summarized in Table 5.

DISCUSSION:

In the current study, a total of 400 medical records of the study subjects were analysed and found that RA was predominant in female patients (79.2%) than in male (20.8%) patients, and the similar results were found in a study conducted by Gurung S et al., Rejimon G et al., Bernatsky S et al.,^9-11. Therefore, it can be explained as the prevalence of RA is known to be comparatively higher in females than in males. Also, study patients were categorised based on their age groups, and the highest frequency of RA was seen in patients belonging to the age group of 50-69, which was also in accordance to the results obtained in the studies conducted by Gurung S et al., Rejimon G et al., Bernatsky S et al.,^9-11. However, a study conducted by Germano V et al.¹² showed a different result wherein the frequency of RA was the highest in patients aged less than 50 years. In addition to that, during the study, length of hospital stay of patients was observed, and it was found that a maximum number of patients was admitted for 1-7 days, and the minimum number of patients was admitted for more than 21days. Out of 400 patient medical records analysed, and it was found that a total of 2856 drugs were prescribed, in which 57.8% of the study subjects were prescribed with 6-10 drugs, and thus the average number of drugs per prescription was found to be 7. Whereas, in the study conducted by Rejimon G et al.,¹⁰the average number of drugs per prescription was found as 3.9. This may be attributed to the difference in prescribing patterns; however, it is ideal to have lesser drugs in the prescriptions to reduce the risk of drug related problems.

In the current study, commonly prescribed classes of drugs for the treatment of RA are Disease-modifying antirheumatic drugs (DMARDs), Corticosteroids, biologic therapies, and Nonsteroidal anti-inflammatory drugs. Among this, Disease Modifying Anti Rheumatic Drugs (DMARDs) were the mostly prescribed agents (39.2%) to manage the disease. Similar results were also seen in studied conducted by Gurung S et al.,⁹ and Bernatsky S et al.,¹¹as the DMARDs are the mainstays in the management of RA. Among all the patients prescribed with DMARDs, it was observed that Methotrexate was the most commonly prescribed (52.7%) DMARD, which was also supported by the results of studies conducted by Bernatsky et al.,¹¹In contrast with this, in studies conducted by Gurung S et al.,⁹ Agarwal S K et al.,¹² Hydroxychloroquine was found to be the most commonly prescribed DMARD and Sulfasalazine followed by Methotrexate was the widely prescribed DMARD according to a Sulaiman W et al.,^13.Therefore,this study concludes that even though there is a difference in opinions in the selection of DMARDs, still they are considered to play a vital role in the management of RA. Furthermore, it was found that among the different classes of Corticosteroids prescribed for the management of RA, Deflazacort (46.8%) was the most highly prescribed whereas in the study conducted by Gurung S et al.,⁹Prednisolone was having the highest prescription frequency and, in a study, conducted by Black R J et al.,¹⁴it was seen that Glucocorticoids were more frequently prescribed. This variation in choice of drug therapy can be attributed to severity, the extent of disease progression, comorbidities, and related problems. Paracetamol (55.4%) was the most prescribed analgesic whereas in studies conducted by Gurung S et al.,⁹and Rejimon G et al.,¹⁰it was found that Tramadol and Etoricoxib were the most commonly prescribed drug and in a study performed by Nagla A et al.,¹⁵it was seen that a combination of Paracetamol + Tramadol was the most commonly prescribed analgesic agent. These studies show that better pain management is achieved by Non-Steroidal anti-inflammatory drugs and synthetic opioids. Whereas the study shows, among all the NSAID, Diclofenac (34.4%) was the most commonly prescribed NSAID which was by the result of studies conducted by Gurung S et al.,⁹and studies conducted by Rejimon G et al.,¹⁰ showed Etoricoxib as the most commonly.

The study also shows the most common associated co-morbidity was Anaemia (30.2%), whereas in studies by Birshi J et al.,⁶Shakti B D et al., ⁷ and Nagla A et al.,¹⁵ Hypertension was the most common associated co-morbidity seen. The types of infections associated with RA were also evaluated in the study, and it was found that Tuberculosis (54.5% each) was the most common infection seen, which was also supported by the results seen in the study conducted by Van Der Veen M J et al., ¹⁶and Germano V et al.,¹²Therefore the results show that use of Biological and traditional DMARDs are associated with higher risk of developing TB.

CONCLUSION:

The prescribing trends in the pharmacological management of RA and its associated comorbidities and infections were analyzed. During the study, it was observed that females were more prone to RA than males, and the most affected age group was found to be 50-69 years. Among the 400 patients included in the study, the majority of the patients were prescribed with DMARDs (39.2%), followed by Analgesics (25.2%) and NSAIDS (22.2%) for the treatment of RA. It was observed that Methotrexate was the most commonly prescribed drug among DMARDs, followed by Hydroxychloroquine sulphate. The use of steroids in the management of RA was less compared to DMARDs. TB was found to be the most common infection in the study population and was managed well by appropriate antibiotic therapy. Therefore, the study provides an insight into the health care providers on the importance of rational use of drugs in the treatment of Rheumatoid arthritis, and the findings will also help various health care providers to get a better understanding of recent trends in the management of RA. This will, in turn, help in minimizing the overall duration of hospital stay as well as the risk of infections associated with RA.

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Received on 23.10.2019 Modified on 29.01.2020

Research J. Pharm. and Tech. 2020; 13(11):5263-5266.

DOI: 10.5958/0974-360X.2020.00920.8