A PROSPECTIVE STUDY OF DRUG UTILIZATION AND QUALITY OF LIFE IN PSORIASIS PATIENTS IN DERMATOLOGY DEPARTMENT OF A TERTIARY CARE TEACHING HOSPITAL

Purpose/aim: To assess the current prescription pattern, efficacy, tolerability and impact on Quality of life(QoL) in psoriasis patients. Material: An observational, prospective study of 18 months was carried out in a tertiary care teaching hospital. Newly diagnosed patients of psoriasis, aged ≥ 18 years were included in the study. The demographic, clinical profile, psoriasis area severity index (PASI) and drug utilization were recorded. Follow up was done at 15 days interval for two and a half months. Patient’s QoL was assessed using Psoriasis Disability Index (PDI). Results: A total 100 patients were enrolled in the study. At the time of diagnosis, 43 patients had PASI score ≤10 and 57 had > 10. At the last follow up 96 patients had PASI sore ≤ 10 and 4 had > 10. Mean of QoL at the time of diagnosis was 10.43 and at the last follow up 6.1. Pre and posttreatment PASI score showed direct intermediate significant correlation with pre and post-treatment QoL score. Most frequently fixed drug combination(FDC)of steroid and keratolytic agent were prescribed followed by anti-histaminics, steroids, minerals, anti-microbial agents, emollients, vitamins, H2-blockers, immunosuppressants, and NSAIDS.WHO core indicators were used to analyse drugs prescribed. Conclusions: In this study, the treatment of psoriasis is according to the “NICE” guideline. Patient’s treatment adherence increased because of the QoL improvement. Thus, the QoL tools are important measure of patient satisfaction and treatment monitoring.


Introduction
Psoriasis is a chronic inflammatory immune mediated proliferative skin disorder characterized by keratinocyte hyperproliferation, vascular endothelial proliferation, and inflammatory cell infiltration. The exact pathogenesis is not well understood, but it is known to be multifactorial, having both genetic and environmental influences. 1 It affects 1-3% of world's population and characterized by sharply marginated scaly, erythematous plaques that develop in a relatively symmetrical distribution. 2 Psoriasis is a serious condition associated with depression and anxiety. It affects patient's lifestyle, employment and social conditions. Thus, it has negative impact on patient's quality of life. Quantification of the impact of psoriasis on the Quality of life(QoL), along with clinical severity assessment, could provide a measure of the clinical efficacy of the dermatological therapies. 3 Surprisingly, very few Indian study have looked into drug utilization pattern and impact on QoL in psoriasis patients. Hence, this study is aimed to assess the current prescription pattern, efficacy, tolerability, cosmetic acceptability of treatment and impact on QoL in psoriasis patients.

Materials and Methods
This was an observational, prospective study of 18 months duration from December 2015 to May 2017.It was carried out in tertiary care teaching hospital, Rajkot after taking permission from Institutional Ethics Committee (IEC) and head of the department of Dermatology and Venereology. Ethical approval was obtained from IEC on 30/11/2015(Letter no.-18689). Patients newly diagnosed as having psoriasis, aged above 18 years were included and patients already on treatment of psoriasis were excluded. Informed written consent of patients was taken before collection of the data.
The baseline data including demographic profile, clinical profile, psoriasis area severity index(PASI)score and drug utilization were recorded from patient's OPD case paper in preformed case record form (CRF). Follow up was done regularly at every 15 days interval for two and half months. During each follow up presenting complaints, drug utilization, PASI score were analysed. Patient's QoL was assessed at first visit and after 5 th follow up visit to evaluate the effect of treatment on it, by investigator by using psoriasis disability index (PDI) which was taken from Department of Dermatology at Cardiff University School of Medicine. Recorded data were analysed by using Microsoft excel 2013 and Graph pad prism 7. Chi square test was applied to see the significance between two variables. D'Agostino-Pearson Omibus normality test was used to check normality of PASI and QoL score. Wilcoxon matched pairs signed rank test was used to see the significance between pre and post treatment PASI and QoL score. Spearman correlation test was used to check the correlation between PASI score and QoL score. P value < 0.05 was considered statistically significant.

Results
A total of 100 patients were included with follow up at 15 days interval for two and half months. Thus a total of 600 prescriptions were analysed. Out of 100 patients, 63 were males and 37 were females. Male to female ratio was 1.7:1.The Mean age of patients was 43.65 ± 13.36 years. Based on Kupuswamy socioeconomic class scale, 81 patients were from middle socioeconomic class and 19 were from lower socioeconomic class. All the patients presented with multiple symptoms. The most common being itching, scaly plaque, powdery scales and burning sensation ( Table  1). History of stress induced exacerbation of disease was present in 6 patients out of which 2 were males and 4 were females. History of sore throat was present in 40 patients, tonsillitis in 6 patients and one patient had both sore throat and tonsillitis. Positive history of smoking, alcohol consumption, and tobacco chewing was present in 29 patients. Family history was positive in 7 patients. Co-morbid conditions like hypertension, diabetes were present in 23 patients, for which the patients were treated with antihypertensives (amlodipine, atenolol, atorvastatin, losartan and metoprolol) and antidiabetics (metformin, glipizide).    Table-2, most frequently prescribed fixed dose combination was steroid and keratolytic agents.  Percentage of drug prescribed by generic name 100% 3.
Percentage of prescription containing fixed dose combination 17.95% 5.
Percentage of drug prescribed from WHO list of Essential Medicines (2015) 48.76% 6.
Percentage of drug prescribed from National List of Essential Medicines (2011)

65.29%
Adverse drug reaction profile: Adverse drug reactions (ADRs) caused by drugs used in the treatment of psoriasis were staining, skin irritation, nausea, and skin dryness. Causality assessment was done by WHO causality scale which indicated that all ADRs were "possible". Severity and preventability of ADRs were assessed with Modified Hartwig and Siegel scale and Schumock and Thornton preventability scale respectively. Out of all ADRs, 23 were of "level 3 severity" and 6 were of "level 2 severity". All the ADRs were 'not preventable' (Table  4). Upper respiratory tract infections especially those caused by streptococci may cause flareup of existing psoriasis or may precipitate an attack of acute guttate psoriasis. 13 Role of bacterial superantigens in the pathogenesis of variant psoriasis has been postulated. 14  In our study Co-morbid conditions like hypertension, diabetes was seen. The exact mechanism underlying these associations is unknown, but it may be due to alterations to the renin-angiotensin system, elevated endothelin-1 level, and increased oxidative stress. 18 Th-1 cytokines that are overproduced in psoriasis are thought to promote insulin resistance as well. 18 The PASI is the most widely used measurement tool for psoriasis. It combines the assessment of the severity of lesions and the area affected into a "single score" in the range of 0 (no disease) to 72 (maximal disease). 10 In our study baseline PASI score was measured and it ranged from 0.3 to 15.7. There was significant improvement seen in patient's PASI score after 2 ½ months of treatment. Thus, PASI was used to assess efficacy of given treatment in psoriasis. Studies done by Ramani YR et al and Raghunandan R et al also showed significant improvement in PASI after 8 weeks and 12 weeks of treatment respectively. 6,8 In our study, we used psoriasis disability index (PDI) to assess QoL of patients. The PDI is calculated by summing the score of each of the 15 questions after four months of treatment. Categorical scores were given to each question according to the severity in which score 3 means "very much" (severe), score 2 means "a lot" (moderate), score 1 means "very little" (mild), and score 0 means "not at all" (unaffected) and the resulting score ranged from 0 to 45. The higher the score, the more QoL is impaired. PDI can also be analysed under five subsets, namely, daily activities, work, personal relationship, leisure and treatment. In our study, percentage of patients affected in particular subset of PDI was measured. Majority of patient's QoL was affected in daily activities (100%) followed by leisure (83%), work (75%), treatment (52%) and personal relationships (13%). These findings were in accordance with the study done by Manjula VD et al in Kottayam which reported the QoL was most affected in "daily activities" (90.6%) followed by "work" (84.4%). 19 In our study, significant improvement was seen in patient's quality of life after 10 weeks of therapy. Correlation between pre-treatment and post-treatment PASI score and QoL were done using Spearman Rank correlation test which shows direct intermediate significant correlation between pre and post-treatment PASI score and QoL score with correlation value (r)-0.3726, and 0.3902 respectively. Similar findings were seen in studies conducted by Gelfand  WHO core indicators were used to analyse drug utilization. The average number of drugs prescribed per prescription was 5.37 which is higher than that reported in previous studies done by Barot 6,9 It is also more than the WHO recommendation (<3/ prescription) indicating a trend of polypharmacy. 23 Polypharmacy is known to cause unnecessary adverse reactions, drug interactions, complications, medication nonadherence, various medication errors, and increased cost of therapy. In our study, 100% drugs were prescribed by generic names which may reduce overall expenditure on drugs and avoiding medication error. According to NICE guideline, treatment of psoriasis varies in all patients depending on the type of psoriasis, severity and body sites involved. First line therapy describes traditional topical therapies like topical steroids, emollients and keratolytics. Second line therapy includes phototherapy and third line therapy includes systemic immunosuppressants. Anti-microbial agents are prescribed at the time of acute exacerbation and infection. Anti-histaminics, H 2 blockers, vitamins, minerals are used as adjuvant drugs. 22

Conclusion
In our study, the treatment of psoriasis is according to the NICE guideline. Patient's adherence to the treatment increased because of the improvement in the Quality of Life (QoL). Thus, the QoL tools are important measure of patient satisfaction and treatment monitoring in the developing world.