Prospective observational study was conducted in the Department of Orthopaedics in collaboration with Department of Pharmacology in a tertiary care teaching hospital over a period of one year (November 2014-December 2015). The study was initiated after obtaining permission from the Institutional Ethics Committee (Code No: 87/2014). Sample size was calculated using the formula 4pq/l² considering 16% improvement in QoL by pharmacotherapy in OA patients [12]. With 10% non-response rates and 95% confidence interval, the sample size was calculated as 256. Confidentiality was maintained throughout the study. Total of 285 eligible patients diagnosed with OA, attending Orthopaedic (outpatient and inpatient) Department at a tertiary care hospital were screened for the study. The details about the study were explained to each patient in their vernacular language. Written informed consent was obtained from all of them. The OA patients were screened and who had met the eligibility criteria were enrolled in the study.

Inclusion criteria

Exclusion criteria

The general physical examination and baseline investigations were advised to rule out any co-morbid medical condition. Patient’s demographic details namely name, age, sex, occupation, address and phone/mobile number were noted. Details of patient complaints, duration of the disease, affected joint and progression of the disease were recorded. Data on drug details in terms of dose, route of administration and duration of the course were also recorded.

The WOMAC index scale was used in OA patients to assess the QoL during their first and second visit after one month (follow-up). WOMAC is widely used by healthcare professionals, a proprietary set of standardised questionnaires to assess OA patients. Patients were explained about the WOMAC index scale in their vernacular language. Literate patients were asked to personally complete the WOMAC index scale and in case of illiterate patients, the questions were asked verbally and their responses were recorded to assess baseline pain characteristics, stiffness factors and physical function parameters. The WOMAC index scale for Indian population (i.e.,) the WOMAC scale modified CRD Pune version was used [14].

Two scales are available in WOMAC index namely: a) Likert scale; and b) Visual analogue scale [15].

Data were entered and analysed using SPSS software version 16.0 version and expressed in descriptive statistics. WOMAC scores (pain, stiffness and physical function) were expressed as mean±standard deviation (SD). WOMAC scores at the first visit and follow-up visit were analysed using student paired t-test. The p-value <0.05 was considered as statistically significant.

A total of 285 OA patients were screened and among them 275 patients who satisfied the eligibility criteria were recruited for the study. Nineteen patients lost their follow-up visits even after sending more than three reminders and finally analysis were done for 256 patients data. Among the study population, females were predominant accounting for 64.8% (166) and 35.2% (90) were males. Majority of the patients 62.9% (161) belonged to the age group of 40 to 60 years. More than half of the patients had bilateral OA knee (58.6%) [Table/Fig-1]. Most frequent co-morbid conditions were hypertension seen in 19 patients (7.4%) followed by diabetes mellitus in 14 patients (5.5%), asthma in 4 patients (1.6%), Coronary Artery Disease (CAD) in 2 patients (0.8%) and hypothyroidism in 2 patients (0.8%). The study observed that about 71.5% (183) of the patients received four and more than four drugs. Only one patient received nine drugs [Table/Fig-2]. Among the various drug class prescribed, NSAIDS (Paracetamol-500 mg TID, Diclofenac-50 mg BID, Aceclofenac-100 mg BID, Ibuprofen-400 mg BID, Indomethacin-25 mg BID, Etodolac-300 mg BID, Ketorolac-60 mg) prescribed were estimated to be 35.8% (379) followed by Opioids (Tramadol-50 gm BID, Tapentedol-100 mg BID) 3.7% (33) and others (Diacerein-50 mg OD) 1.3% (14), gastro protective agents 23.1% (244), calcium supplements 16.3% (172), multivitamins 16.5% (174). Ferrous sulfate, Pregabalin, Trypsin, Atorvastatin were the other drugs 3.9% (42) out of 1058 drugs used for OA patients [Table/Fig-3]. The common route of drug administration in OA patients was oral in 220 patients (85.9%) followed by intramuscular in 21 patients (8.2%) and topical in 15 patients (5.9%). There was statistically significant reduction in the pain, stiffness and physical function score in the follow-up visit when compared to first visit (p<0.0001) after a month of pharmacotherapy [Table/Fig-4]. Statistically significant reduction in WOMAC score was also observed in the follow-up visit when compared to first visit for Aceclofenac and Paracetamol, Diclofenac, Tramadol with Paracetamol, Etodolac with Paracetamol, Paracetamol (p<0.0001) and Diacerein (p<0.01) [Table/Fig-5,6]. Percentage reduction in Womac score was calculated from first visit and follow-up visit scores using the formula P=a/b×100 where P is Percentage reduction, a is reduction difference between first and follow-up visit and b is original percentage value that was reduced. Based on this Pain, Stiffness and Physical function scores, reduction was 28%, 17%, 20%, respectively.

Two hundred and fifty six OA patients completed the present study with female preponderance (64.8%) as supported by Gupta R et al., and Poornima B et al., [1,16]. This female predominance was the major risk factor for OA and this could be due to their lack of physical activity, mobility and social issues. Majority of the patients (62.9%) were in the age group of 40 to 60 years which is similar to the study conducted by Gurung S et al., [17]. Dominance of knee OA with the duration of illness being 1 to 3 years (42.2%) was observed in the present study and this could be attributed with probable excessive use of squatting and cross-leg sitting positions in Indian customs. The present study results were comparable with the study conducted by Poornima B et al., and Venkatachalam J et al., where knee joint was commonly involved in OA [16,18]. The most frequent co-morbid conditions were hypertension, diabetes, CAD, asthma and hypothyroidism which was similar to study done by Gurung S et al., [17].

Pharmacological treatment is aimed to relieve the signs and symptoms and indeed, to reduce the disease progression with improvement in QoL. Based on this, the most frequently prescribed drug class was NSAIDs similar to the study done by Sahayam JSA et al., where NSAIDs were commonly prescribed [19]. Gastro protective agents were commonly prescribed in OA patients to prevent non-selective NSAIDs induced Gastrointestinal adverse effects and also calcium supplements were prescribed to increase bone strength in the OA patients which was in accordance with study done by Poornima B et al [16]. Paracetamol was most frequently prescribed as combination therapy along with Aceclofenac, Tramadol and Etodolac whereas Diclofenac was commonly used as monotherapy. In contrast to present study, Poornima B et al., study showed Etoricoxib and Aceclofenac were the frequently prescribed drug as monotherapy and among the combination therapy, Paracetamol was prescribed with Aceclofenac, Diclofenac and Tramadol as compared with present study observation [16]. Tramadol combined with paracetamol has been used in only 32 patients (12.5%) in the present study.

This study utilised modified WOMAC index-CRD Pune version to assess the QoL which showed significant reduction in the pain, stiffness and physical function scores in the follow-up visit when compared to first visit with 28% reduction in pain score, 17% reduction in stiffness score and 20% reduction in physical function score, after a month of pharmacotherapy which is the supporting evidence for the efficacy of the NSAIDs being used globally. Jadhav MP et al., reported using WOMAC score that there were 20%, 30% and 16% reduction in pain subscale, stiffness and physical function, respectively after 12 weeks of pharmacotherapy in their study [12]. This reduction was in the all three domains in WOMAC score with 12 weeks of pharmacotherapy as compared with 4 weeks of therapy in the present study.

It was also observed that combination of Aceclofenac with Paracetamol had caused significant reduction in all the three subscales of WOMAC score during follow-up visit when compared to first visit (p<0.0001). The study result was in accordance with Kanaki AR et al., who observed that Aceclofenac treated patients had statistically significant reduction (p<0.0001) in WOMAC scores when compared to Diclofenac group at the end of third month [20]. The improvement in WOMAC score with Aceclofenac therapy is attributed to its easy penetration into inflammatory tissue, such as joints and effectively suppressing prostaglandin production by the inhibition of cyclooxygenase (COX-1 and COX-2) enzyme with moderate selectivity for COX-2 inhibition. It also possesses inhibiting action on IL-β which in-turn has stimulatory effect on synthesis of cartilage matrix. Invitro studies have shown that, Aceclofenac causes stimulation of glycosaminoglycan synthesis in human osteoarthritic cartilage and protects chondrocytes. The anti-inflammatory effect of Aceclofenac could also be due to inhibition of various mediators like IL-6 and tumour necrosis factor in human osteoarthritic synovial cells and articular chondrocytes. It was also found that inhibition of reactive oxygen species ion and expression of cell adhesion molecules in human neutrophils ascribed to the action of Aceclofenac [21]. Paracetamol, a simple analgesic with minimal anti-inflammatory action was frequently recommended as a first line drug in the treatment of OA. This study also showed that Paracetamol significantly improved the pain and physical function score (p<0.0001) during follow-up when compared to first visit. However, reduction in stiffness score was not significant (p=0.268) in Paracetamol during follow-up visit [Table/Fig-6]. Paracetamol acts by inhibiting the COX isoenzymes and exhibits poor anti-inflammatory action [22]. Animal studies have shown that paracetamol modulates descending serotoninergic pathways involved in inhibition of pain sensation. It was also found that paracetamol inhibit L-Arginine/NO pathway in the nociceptive processes of the spinal cord that are activated by Substance P and N-methyl-D-aspartate receptors [23]. Surprisingly, this study also indicated that Coxibs were not prescribed in any of the patients with OA which could be due to their adverse effects. In addition to pharmacotherapy, patient’s education about the disease and beneficial role of other non-pharmacological measures like exercise should also be emphasised.

Though this study had demonstrated the improvement of QoL by pharmacotherapy, the OA patients were followed-up for one month only which has become the constraint of the present study. Moreover, present study was a hospital based study and not a community based with limited sample size. Regular prescription analysis should be recommended in larger sample size with repeated follow-ups in order to improve the awareness and enable suitable modification in the prescription of OA patients to increase the therapeutic benefits.

The study indicates that there is a significant improvement in QoL of the patients determined by WOMAC score (pain, stiffness and physical function) after a month of pharmacotherapy. Aceclofenac with paracetamol combination therapy and Diclofenac monotherapy were most frequently prescribed among the NSAIDs. Safety is the proven concern in treating chronic conditions in OA, hence Aceclofenac and Paracetamol is recommended as combination therapy. To infer, this study indicates that oral NSAIDs when promptly used could provide promising relief of pain, improve physical function and QoL.