Real-World Effectiveness and Safety of Etoricoxib in Patients with Chronic Musculoskeletal Pain: An Observational Cohort Study > 자유게시판

Abstract

Background: Etoricoxib, a selective cyclooxygenase-2 inhibitor, is widely used for pain and inflammation, but real-world data on its long-term effectiveness and tolerability remain limited. This observational study aimed to evaluate the clinical outcomes and adverse events associated with etoricoxib in a routine care setting. Methods: We conducted a retrospective cohort study using electronic medical records from two tertiary hospitals between January 2020 and December 2023. Adults with chronic musculoskeletal pain (osteoarthritis, rheumatoid arthritis, or chronic low back pain) who initiated etoricoxib (60–120 mg/day) were included. Outcomes included pain improvement (numerical rating scale reduction ≥2 points at 3 months), discontinuation rates, and adverse events (gastrointestinal, cardiovascular, renal). Cox proportional hazards models were used to identify predictors of discontinuation. Results: A total of 1,248 patients were analyzed (mean age 58.4 years, 62% female). At 3 months, 74% achieved clinically meaningful pain reduction. The median treatment duration was 8 months (IQR 4–14). Discontinuation occurred in 38% (n=474), primarily due to lack of efficacy (18%) or adverse events (14%). Gastrointestinal adverse events were most common (10%), followed by hypertension (5%) and pedal edema (3%). Cardiovascular events occurred in 1.2% (n=15). Age >65 years (HR 1.32, 95% CI 1.08–1.61) and baseline hypertension (HR 1.45, 95% CI 1.18–1.79) were associated with higher discontinuation risk. Conclusion: In this real-world setting, etoricoxib provided effective pain relief for most patients, but a substantial proportion discontinued therapy due to lack of efficacy or adverse events. Gastrointestinal and cardiovascular risks warrant careful patient selection and monitoring.

Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) are cornerstone therapies for chronic musculoskeletal pain. However, traditional NSAIDs carry risks of gastrointestinal (GI) ulceration and bleeding due to non-selective cyclooxygenase (COX) inhibition. Selective COX-2 inhibitors (coxibs), such as etoricoxib, were developed to reduce GI toxicity while preserving anti-inflammatory efficacy. Etoricoxib has demonstrated efficacy in osteoarthritis, rheumatoid arthritis, and acute pain in randomized controlled trials (RCTs). Yet RCTs often exclude complex patients with comorbidities, limiting generalizability. Real-world observational studies are needed to understand how etoricoxib performs in routine clinical practice—including patterns of use, effectiveness, tolerability, and predictors of treatment persistence. This study aimed to describe the real-world experience of etoricoxib in a diverse cohort of patients with chronic musculoskeletal pain.

Methods

Study Design and Setting: Retrospective observational cohort study using electronic health records (EHRs) from two large tertiary hospitals. Data were extracted from January 2020 to December 2023. The study was approved by the institutional review board.

Population: Adults (≥18 years) with a diagnosis of osteoarthritis (knee, hip, or hand), rheumatoid arthritis, or chronic low back pain (≥3 months) who were prescribed etoricoxib for the first time (no prior coxib use in previous 6 months). Patients with prior GI bleeding, cardiovascular events within 6 months, or estimated glomerular filtration rate <30 mL/min were excluded.

Exposure: Etoricoxib dose was classified as standard (60 mg/day) or high (90–120 mg/day) based on initial prescription. Duration and adherence were assessed via prescription refill records.

Outcomes: Primary effectiveness outcome was pain improvement at 3 months, defined as a ≥2-point reduction on the 0–10 numerical rating scale (NRS) compared to baseline. Secondary outcomes included treatment discontinuation (stopping etoricoxib for ≥30 days) and reasons (lack of efficacy, adverse events, patient choice, physician decision). Safety outcomes included any adverse event leading to dose reduction or discontinuation, specifically GI (dyspepsia, nausea, abdominal pain, bleeding), cardiovascular (hypertension, edema, myocardial infarction, stroke), renal (acute kidney injury), and hepatic (transaminase elevation >3 times upper limit).

Statistical Analysis: Descriptive statistics summarized baseline characteristics. Kaplan-Meier methods estimated time to discontinuation. Multivariable Cox regression examined predictors of discontinuation (age, sex, comorbidity burden, baseline NSAID use, etoricoxib dose). Sensitivity analyses were performed for patients with different pain diagnoses. All analyses used R version 4.2.

Results

Baseline Characteristics: Among 1,248 patients, mean age was 58.4 years (SD 14.2); 62% were female. Most common diagnoses: osteoarthritis (54%), chronic low back pain (28%), rheumatoid arthritis (18%). Mean baseline pain NRS was 6.7 (SD 1.8). Comorbidities included hypertension (35%), diabetes (18%), and prior NSAID use (72%). Standard-dose etoricoxib (60 mg) was prescribed for 81% of patients; 19% received 90–120 mg. Median follow-up was 12 months (IQR 6–18).

Effectiveness: At 3 months, 74% of patients (95% CI 71–77) achieved a ≥2-point pain reduction. Mean NRS decreased from 6.7 to 3.7 (mean difference –3.0, p<0.001). Similar improvements were observed across diagnostic subgroups. Among those with available data at 6 months (n=682), 68% maintained improvement.

Treatment Discontinuation: Overall, 38% discontinued etoricoxib during follow-up (incidence rate 0.64 per person-year). Median time to discontinuation was 11 months. Reasons: lack of efficacy (18% of all patients), adverse events (14%), patient choice (4%), and physician decision (2%). Discontinuation was higher in patients with rheumatoid arthritis (45%) compared to osteoarthritis (35%) and low back pain (34%) (p=0.01).

Adverse Events: A total of 312 adverse events were reported. GI events were most frequent (10% overall): dyspepsia (4.5%), abdominal pain (3.0%), diarrhea (1.5%), and GI bleeding (0.6%; n=8). Hypertension (new-onset or worsening) occurred in 5% of patients; pedal edema in 3%. Cardiovascular events (myocardial infarction, stroke, or arterial thromboembolism) occurred in 1.2% (n=15). Renal adverse events (acute kidney injury or fluid retention) affected 1.5%. Hepatic transaminase elevation occurred in 0.8%. No fatal events were attributed to etoricoxib.

Predictors of Discontinuation: In multivariable analysis, age >65 years (HR 1.32, 95% CI 1.08–1.61), baseline hypertension (HR 1.45, 95% CI 1.18–1.79), and higher baseline pain severity (NRS ≥8) (HR 1.21, 95% CI 1.00–1.46) were significantly associated with increased risk of discontinuation. High-dose etoricoxib (≥90 mg) showed a trend towards higher discontinuation (HR 1.18, 95% CI 0.96–1.45, p=0.11). Female sex and concurrent use of proton pump inhibitors were not significantly associated.

Discussion

This observational study provides a comprehensive real-world assessment of etoricoxib in chronic musculoskeletal pain. Three-quarters of patients reported meaningful pain relief at 3 months, corroborating RCT evidence. However, nearly 40% discontinued therapy, primarily due to inefficacy or adverse events. This discontinuation rate is higher than reported in some controlled trials, likely reflecting a less selected patient population and longer follow-up.

The adverse event profile mirrors known COX-2 risks: GI symptoms remained common, though serious GI bleeding was rare (<1%). Hypertension and edema were notable, consistent with etoricoxib’s dose-dependent effect on blood pressure. Cardiovascular events were infrequent but present, reinforcing caution in patients with pre-existing cardiovascular risk. Our finding that baseline hypertension predicted discontinuation underscores the need for blood pressure monitoring.

Comparison with other coxibs: etoricoxib’s 74% pain response is similar to that of celecoxib in real-world studies, but the GI event rate (10%) is lower than with non-selective NSAIDs. The relatively high discontinuation due to lack of efficacy (18%) may reflect inadequate dosing or irreversible joint damage.

Limitations include retrospective design, potential selection bias, incomplete data on over-the-counter NSAID use, and lack of a comparator. Residual confounding may affect predictor analyses. Nevertheless, the large sample, long follow-up, Clenbuterol 40mcg prezzo basso €2.16 : Clenbuterol (doctorpool.it) and clinically relevant outcomes enhance generalizability.

Conclusion

In routine practice, etoricoxib provides effective pain relief for most chronic musculoskeletal pain patients, but a substantial minority discontinue due to inefficacy or adverse events. Older age, hypertension, and severe baseline pain increase discontinuation risk. These findings support the use of etoricoxib with careful patient selection and monitoring of blood pressure, renal function, and GI symptoms. Future prospective observational studies should include patient-reported outcomes and longer-term cardiovascular safety.