Lower limb degenerative arthritis, most commonly presenting as osteoarthritis of weight-bearing joints, is a major cause of chronic pain, mobility restriction, and disability worldwide [1]. It is now recognized as a whole-joint disorder involving cartilage, subchondral bone, synovium, and periarticular structures rather than an isolated cartilage disease [2]. In India, the burden is substantial and continues to rise with population ageing, occupational joint stress, and increasing chronic disease burden [3].

Current management emphasizes non-pharmacological measures such as exercise, rehabilitation, and weight reduction, but many patients continue to experience persistent symptoms requiring pharmacological treatment [4]. Nonsteroidal anti-inflammatory drugs remain an important option for symptomatic relief, and selective cyclooxygenase-2 inhibitors such as etoricoxib are widely used because they provide effective analgesia with improved gastrointestinal tolerability compared with non-selective agents [5]. Clinical trials have demonstrated that etoricoxib improves pain and physical function in osteoarthritis [6], and real-world evidence has also supported its effectiveness in routine practice [7].

Despite its widespread use, there is limited short-format real-world evidence from Indian tertiary-care settings evaluating pain, function, and safety together in the same cohort. The present study was therefore undertaken to evaluate the efficacy and safety of etoricoxib in patients with lower limb degenerative arthritis by assessing changes in pain intensity and functional status over time, along with structured monitoring of adverse drug reactions.

MATERIALS AND METHODS

This prospective, observational, single-arm study was conducted at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, in collaboration between the Departments of Pharmacology and Orthopaedics, after approval from the Institutional Ethics Committee (IEC No. 85/24). Patients attending the Orthopaedics outpatient department with lower limb degenerative arthritis were screened for eligibility and enrolled after written informed consent. Eligible participants were aged 50–70 years, of either sex, and had unilateral or bilateral degenerative arthritis involving the lower limb. Patients with limb deformity, inflammatory arthritis, life-threatening comorbid illness, bleeding or coagulation disorders, or malnutrition were excluded. A total of 98 patients were enrolled by purposive sampling. Baseline evaluation included age, sex, height, weight, body mass index (BMI), and comorbidities. Pain intensity was assessed using the Visual Analog Scale (VAS) [8], and functional status using the Lower Extremity Functional Scale (LEFS) [9]. All patients received etoricoxib 60 mg twice daily with physical therapy for 4 weeks, followed by physical therapy alone for a further 4 weeks. Follow-up assessments were performed at week 4 and week 8. Adverse drug reactions (ADRs) were monitored throughout the study and causality was assessed using the WHO–UMC system [10]. Continuous variables were expressed as mean ± SD or median (IQR), and categorical variables as frequency and percentage. VAS scores were analyzed using the Friedman test with Wilcoxon signed-rank post-hoc comparisons, while LEFS scores were analyzed using paired t-tests. A p value <0.05 was considered statistically significant.

RESULTS

Baseline characteristics

A total of 98 patients were included in the final analysis. Females comprised 60.2% of the study population. The median age was 55.0 (IQR 52.0–60.0) years, and mean BMI was 26.81 ± 3.41 kg/m². Hypertension was the most common comorbidity, followed by diabetes mellitus and thyroid disorder. These findings indicate that the study population largely represented middle-aged to older adults with symptomatic lower limb degenerative arthritis and relevant cardiometabolic comorbidity burden.

Table 1. Baseline characteristics of the study population (N = 98)

Efficacy outcomes

Pain intensity showed significant improvement over time. Median VAS score decreased from 6.0 (IQR 6.0–7.0) at baseline to 5.0 (4.0–5.0) at week 4 and remained 5.0 (4.25–6.0) at week 8. Friedman test showed a significant difference across the three time points (χ² = 168.20, df = 2, p<0.001). On pairwise comparison, pain decreased significantly from baseline to week 4 and from baseline to week 8 (both p<0.001), while a small but significant worsening was observed between week 4 and week 8 (p<0.01).

Functional status improved progressively throughout follow-up. Mean LEFS score increased from 39.03 ± 7.87 at baseline to 50.15 ± 7.86 at week 4 and 55.02 ± 7.40 at week 8. Pairwise analysis showed significant improvement from baseline to week 4 (mean difference 11.12; t = 49.37; p<0.001), baseline to week 8 (mean difference 15.99; t = 54.54; p<0.001), and week 4 to week 8 (mean difference 4.87; t = 29.03; p<0.001).

Table 2. Main efficacy outcomes over follow-up (N = 98)

Safety

ADRs were reported in 21 of 98 patients (21.4%). The most frequent ADRs were headache and dyspepsia/epigastric discomfort, with 7 cases each. Other less frequent events included raised blood pressure (3 cases), pedal edema (2 cases), nausea (1 case), and diarrhoea (1 case). Most ADRs were mild or moderate in severity. On WHO–UMC assessment, 10 ADRs were classified as probable/likely, 7 as possible, 2 as certain, and 2 as unlikely. All reported ADRs recovered, and no long-term sequelae were observed.

DISCUSSION

The present study showed that etoricoxib was associated with significant improvement in both pain intensity and functional status in patients with lower limb degenerative arthritis. VAS scores decreased significantly by week 4 and remained lower than baseline at week 8, while LEFS scores improved progressively across all follow-up points. These findings are consistent with randomized trials showing that etoricoxib provides effective symptomatic relief in osteoarthritis and improves physical function in routine clinical use [11,12].

An important finding in the present study was the pattern observed after drug discontinuation. Although a small worsening in pain was seen between week 4 and week 8, VAS scores remained significantly better than baseline, and functional improvement continued during this period. This suggests that early analgesic control with etoricoxib may help patients participate more effectively in continued physical therapy, thereby supporting longer-term functional recovery. Such an interpretation is clinically plausible within current osteoarthritis management strategies, which emphasize multimodal treatment and the central role of exercise and rehabilitation [4,13].

The improvement in LEFS scores is particularly relevant because functional recovery is a major treatment goal in degenerative joint disease. In the present study, function improved not only during active etoricoxib treatment but also during the subsequent rehabilitation-only phase, indicating that symptom control and physical therapy may have acted synergistically. This finding is in line with previous studies showing improvement in physical function and quality of life with etoricoxib in osteoarthritis, including older patient populations and short-term interventional settings [14,15].

With regard to safety, ADRs were observed in 21.4% of patients, and the overall tolerability profile was acceptable. The most frequent events were headache and dyspepsia/epigastric discomfort, most reactions were mild to moderate, and all recovered without long-term sequelae. This pattern is broadly compatible with the known safety profile of etoricoxib, particularly its gastrointestinal tolerability profile when used appropriately [16]. The use of WHO–UMC causality assessment added methodological strength to safety evaluation [10]. The study should, however, be interpreted in light of its limitations, including single-arm design, modest sample size, single-center setting, and short follow-up. Overall, the findings support the pragmatic use of etoricoxib for short-term symptom control as part of a combined pharmacological and rehabilitation-based approach.

CONCLUSION

In this prospective single-arm study, etoricoxib was associated with significant short-term reduction in pain and progressive improvement in functional status in patients with lower limb degenerative arthritis. Pain relief achieved during the first 4 weeks remained better than baseline at week 8, while functional improvement continued even after drug discontinuation during ongoing physical therapy. Adverse drug reactions were observed in a minority of patients, were largely mild to moderate, and all recovered without long-term sequelae. Overall, these findings support the pragmatic use of etoricoxib as part of a combined pharmacological and rehabilitation-based approach for short-term symptomatic management in selected patients with lower limb degenerative arthritis.

REFERENCES

1. Hunter DJ, Bierma-Zeinstra SMA. Osteoarthritis. Lancet. 2019;393(10182):1745-59.
2. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64(6):1697-707.
3. Singh A, Das S, Chopra A, Danda D, Paul BJ, March L, et al. Burden of osteoarthritis in India and its states, 1990-2019: findings from the Global Burden of Disease Study 2019. Osteoarthritis Cartilage. 2022;30(8):1070-8.
4. Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578-89.
5. Arden NK, Perry TA, Bannuru RR, Bruyère O, Cooper C, Haugen IK, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2021;17(1):59-66.
6. Leung AT, Malmstrom K, Gallacher AE, Sarembock B, Poor G, Beaulieu A, et al. Efficacy and tolerability profile of etoricoxib in patients with osteoarthritis: a randomized, double-blind, placebo and active-comparator trial. J Rheumatol. 2002;29(8):1623-30.
7. Lin HY, Cheng TT, Wang JH, Lee SH, Wang CR, Chen DY, et al. Etoricoxib improves pain, function and quality of life: results of a real-world effectiveness trial. Int J Rheum Dis. 2010;13(2):144-50.
8. Langley GB, Sheppeard H. The visual analogue scale: its use in pain measurement. Rheumatol Int. 1985;5(4):145-8.
9. Binkley JM, Stratford PW, Lott SA, Riddle DL. The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. Phys Ther. 1999;79(4):371-83.
10. The use of the WHO-UMC system for standardised case causality assessment. Uppsala: Uppsala Monitoring Centre; 2013.
11. Wiesenhutter CW, Boice JA, Ko A, Sheldon EA, Murphy FT, Wittmer BA, et al. Evaluation of the comparative efficacy of etoricoxib and ibuprofen for treatment of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2005;80(4):470-9.
12. Puopolo A, Boice JA, Fidelholtz JL, Littlejohn TW 3rd, Miranda P, Berrocal A, et al. A randomized placebo-controlled trial comparing the efficacy of etoricoxib 30 mg and ibuprofen 2400 mg for the treatment of patients with osteoarthritis. Osteoarthritis Cartilage. 2007;15(12):1348-56.
13. Raposo F, Ramos M, Cruz AL. Effects of exercise on knee osteoarthritis: a systematic review. Musculoskeletal Care. 2021;19(4):399-435.
14. Huang WN, Tso TK. Etoricoxib improves osteoarthritis pain relief, joint function, and quality of life in the extreme elderly. Bosn J Basic Med Sci. 2018;18(1):87-94.
15. Moss P, Benson HA, Will R, Wright A. Fourteen days of etoricoxib 60 mg improves pain, hyperalgesia and physical function in individuals with knee osteoarthritis: a randomized controlled trial. Osteoarthritis Cartilage. 2017;25(11):1781-90.
16. Feng X, Tian M, Zhang W, Mei H. Gastrointestinal safety of etoricoxib in osteoarthritis and rheumatoid arthritis: a meta-analysis. PLoS One. 2018;13(1):e0190798.