Title

 

Authors

G. Minisola

Unità Operativa Complessa di Reumatologia
Ospedale di Alta Specializzazione “San Camillo”, Roma

 

Abstract

Rheumatic diseases are highly prevalent conditions, affecting more than 10% of the Italian population. Their prevalence is progressively rising, owing to an increase in life expectancy, an increased prevalence of obesity, and an increment of detrimental lifestyles, including poor physical activity and unhealthy dietary habits. Among chronic degenerative rheumatic diseases, osteoarthritis (OA) is the most common, while rheumatoid arthritis (RA) predominates as rheumatic inflammatory disorder. The main symptoms, characterizing both conditions, include pain and functional limitations. The burden of symptoms has a significant impact on daily activities and quality of life, and it requires frequent interaction between patients and physicians. Total expenditure associated with OA and RA ranges between 1.5 and 2.0% of western countries GDP, a major portion resulting from indirect costs, mainly attributable to chronic disability. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for symptomatic treatment of several rheumatic diseases. Their anti-inflammatory and analgesic effects are associated with different safety profiles, depending on their specific pharmacokinetica and pharmacodynamic patterns. NSAID use is associated with adverse reactions in the upper and lower gastrointestinal (GI) tract, including dyspepsia, non-symptomatic lesions, symptomatic ulcers, bleeding and perforations. NSAID effects on the lower GI tract, often underestimated, are associated with significant morbidity and increased mortality rate. The need for effective therapies with good GI safety profile led to the discovery of “coxibs”, selective COX-2 inhibitors able to ensure the analgesic and anti-inflammatory therapeutic benefits of traditional non-selective NSAIDs with a lower risk of GI complications, due to their lack of inhibitory effect on COX-1. Extensive clinical data support the anti-inflammatory and analgesic properties of coxibs and the lower risk of GI damage associated with their use. In 2006, the U.S. Agency for Healthcare Research performed a systematic literature review on non-opioid analgesics, NSAIDs and coxibs, concluding that acetaminophen is less effective than traditional NSAIDs and coxibs in reducing pain and improving functional capacity in OA patients. At that time, the PACES Study had shown results going in the same direction: celecoxib was more effective than acetaminophen, and better accepted by patients (preferred treatment: celecoxib 54% vs acetaminophen 24%). As compared with traditional NSAIDs, celecoxib is associated with a lower rate of GI symptoms (moderate-to-severe abdominal pain, dyspepsia and nausea) and, owing to its good tolerability, it is particularly suitable for long-term treatments. Upon comparison with active controls, randomized trials have shown significantly fewer endoscopically-evident lesions, symptomatic ulcers and upper GI complications in celecoxib-treated patients. Celecoxib appears also to be the only coxib displaying better tolerability than NSAIDs plus proton pump inhibitors throughout the whole GI tract. Treatment with coxibs should be considered for the symptomatic treatment of chronic rheumatic diseases (such as OA, RA, ankylosing spondylitis and gout), particularly when traditional NSAIDs are contraindicated due to risk factors for GI adverse events or previous therapeutic interventions with other drugs were ineffective or barely tolerated. In all cases, according to current criteria of good clinical practice, before starting a treatment with NSAIDs or coxibs the overall risk for both GI and cardiovascular adverse events should be assessed. At the same time, defeatist attitudes, leading to conditions of so-called "therapeutic paralysis", must be avoided. Physicians should rather be aware that a proper assessment of risk-benefit ratio is the basis of rational drug selection, which must always be customized to identify the most suitable and appropriate treatment for individual patients.