Oral NSAIDs

Among the 34 high-quality, 23 moderate-quality, and 1 low-quality studies that met the inclusion criteria, non-selective and selective clyclooxygenase-2 (COX-2) oral nonsteroidal anti-inflammatory drugs (NSAID) consistently improved pain and function compared to controls in the treatment of osteoarthritis of the knee (Reginster 2017; Lee 2017; Gordo 2017; Strand 2017; Essex 2014; Kongtharvonskul 2016; Altman 2015; Gibofsky 2014; Ishijima 2014; Conaghan 2013; Essex 2012; Singh 2012; Elsaman 2016; Schnitzer 2011; Kivitz 2004; Fleischmann 1997; Lee 1986; Davies 1999; Sandelin 1997; Puopolo 2007; Gibofsky  2003; Bensen 1999; Kivits 2002; Clegg 2006; Sangdee 2002; Sheldon 2005; Tannenbaum 2004; Lehmann 2005; Rother 2007; Simon 2009; Svensson 2006; Schnitzer 2010; Doherty 2011; McKenna  2001 (a); Paul 2009; Bolten 2015; Essex 2016; Ekman 2014; Ohtori 2013; Selvan 2012; Pavelka 2007; Ehrich 1999; Lee 1985; Dwicandra 2018; Asmus 2014; Smugar 2006; Bingham 2007; Altman 1998; Schnitzer  1999; Birbara 2006; Williams 2001; Miceli 2004; Mckenna 2001 (b); Pincus 2004; Lohmander 2005; Schnitzer 2005b; Williams 2000; Fleischmann 2006). Although meta-analysis of non-selective oral NSAIDs compared to controls demonstrated a meaningful reduction in pain, the results need to be interpreted with caution due to the relatively high degree of heterogeneity. The meta-analysis of non-selective oral NSAIDs compared to controls demonstrated a meaningful improvement in function with an acceptable degree of heterogeneity. In terms of selective COX-2 oral NSAIDs, the meta-analysis of celecoxib, the only available selective COX-2 oral NSAID on the United States market, demonstrated a meaningful reduction in pain and improved function with an acceptable degree of heterogeneity. The comparison of non-selective and selective COX-2 oral NSAIDs shows no significant difference in the effectiveness between the types of oral NSAIDs (Gordo 2017; Essex 2014; Essex 2016; Essex 2012; Bensen 1999; Kivits 2002; Kivitz 2004; Puopolo 2007; Hochberg 2011; Mckenna 2001 (b); Schnitzer 2005b; Malik 2017). Although NSAIDs effectively reduce pain and improve function in the treatment of osteoarthritis of the knee, providers should consider patient comorbidities, the type of NSAID administered, dose, and duration of administration. In fact, the United States Food and Drug Administration (FDA) has a black-box warning for NSAIDs citing an increased risk of serious cardiovascular thrombotic events and serious gastrointestinal events. Therefore, we recommend the lowest effective dose for the shortest duration possible for the patient. Although selective COX-2 oral NSAIDs were developed to reduce gastrointestinal adverse events compared to non-selective oral NSAIDs, meta-analysis did not reveal a significant reduction in gastrointestinal adverse events.

Benefits/Harms of Implementation

Although oral NSAIDs are widely used to treat osteoarthritis of the knee, providers must recognize the specific risks associated with each medication. Specific patient contraindications need to be assessed on an individual basis (Example: patient with cardiac conditions have an increased risk of myocardial infarction). 

Outcome Importance

The most important consideration will be removal of oral narcotics from the medications prescribed in the treatment of osteoarthritis of the knee. This becomes particularly significant due to the rise of the opioid epidemic in the United States.

Cost Effectiveness/Resource Utilization

Evidence based decision making in selecting the optimal systemic treatment for the treatment of symptomatic knee osteoarthritis should result in improved pain and function. For a given systematic treatments as effectiveness increases without raising the risk of adverse events so will its cost-effectiveness. To date, the most cost-effective systemic treatment is still to be determined.

Acceptability

Currently oral NSAIDs are commonly utilized approach in treating symptomatic knee osteoarthritis, hence there should be no issues implementing this recommendation as it does not influence a major change in clinical practice, and it provides further evidence to support and guide these practices. 

Feasibility

This recommendation may be implemented immediately having a potential positive impact in clinical practice.

Future Research

Most important future research will provide high quality investigation through either prospective randomized trials or prospective cohort studies to establish efficacy within specific subgroups and populations to tailor systemic medications increasing efficacy and decreasing risk of adverse effects