Not all NSAIDs are created equal: How do they differ?

20160825060000, Mak Wen Yao 
NSAIDs, Pain Killer, side effects
Not all NSAIDs are created equal: How do they differ?
Nonsteroidal anti-inflammatory drugs, or NSAIDs, are widely used to treat pain and inflammation due to their documented efficacies. Typically they are an integral part of the treatment plan for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, soft-tissue injuries, back pain, gout, dental pain or even common headache. There is at least half a dozen of different types of NSAIDs available, and each one comes in different strengths and forms. In addition, clear distinctions in terms of efficacies and side effects may not be well known to many people, even healthcare professionals may sometimes find them confusing. Heavy advertisement and campaigning by pharmaceutical companies also helped to spread incorrect perceptions that newer classes of selective NSAID, in particular, are more effective than other "traditional" NSAIDs (1).

In this article, we attempt to provide an overview of the efficacies and side effect profiles of different NSAIDs in order to help doctors and pharmacists to select an appropriate treatment regimen.

Mechanism of action and classification of NSAID

NSAIDs work by inhibition of the pro-inflammatory enzyme cyclo-oxygenase (COX) (2). The COX enzyme can be further classified into two categories: COX-1 and COX-2. Nonselective NSAIDs, otherwise known as traditional NSAIDs, indiscriminately bind to both isomers. Newer selective NSAIDs, however, are capable to selectively inhibit COX-2 only (2).

Efficacies of NSAIDs

A Drug Effectiveness Review Project was undertaken by the Oregon Health & Science University in 2010. The project compared approximately 160 related publications and discovered that, for pain relief in the short-term (or less than 6 months), all different types of NSAIDs had similar efficacies with no significant difference (3). The finding was based on pain reduction in the adult population which suffer from chronic pain of osteoarthritis, rheumatoid arthritis, soft-tissue pain, back pain and ankylosing spondylitis. The group also discovered no difference between oral and topical formulations of NSAIDs. Most interestingly, the results indicated no difference in efficacy for the use of celecoxib up to 800mg a day compared to nonselective NSAIDs. For partially selective NSAIDs such as meloxicam and nabumetone, their efficacies were also demonstrated to be on par with each other.

Another group of scientists, the Oxford pain group, had a slightly different approach to this problem. They constructed the Oxford League Table of Analgesic Efficacy to compare analgesics in acute pain by using the parameter known as the number-needed-to-treat (NNT). NNT represents the number of patients that need to be treated to achieve at least 50% pain relief compared to placebo (2) On the top of the list is ibuprofen 800mg with an NNT of 1.6, followed by diclofenac 100mg with NNT of 1.9. Codeine (not a NSAID) was at the bottom of the chart with an NNT of 16.7 (4).

Side effects

The appropriate use of NSAIDs should not solely rely on their efficacies alone; side-effect profiles should be rightly taken into considerations. Healthcare professionals must be aware of the two main problems of NSAID: Gastrointestinal events, and thrombotic events.

Gastrointestinal Events
The bottom line here is that all NSAIDs are associated with significant risk of gastrointestinal toxicity regardless of their types. Piroxicam, ketoprofen and ketorolac were found to associate with the highest risk while ibuprofen when taken at a low or moderate dose, was associated with the lowest risk of GI events. Indometacin, diclofenac and naproxen were associated with intermediate risks (5).

Selective COX-2 inhibitors were found to associate with a lower risk of GI events compared to nonselective NSAIDs in general (3,5).

Thrombotic Events

Similarly, all NSAIDs are associated with a small increase in the risk of having a thrombotic event. COX-2 inhibitors are particularly at risk, together with diclofenac (at 150mg daily) and ibuprofen (at 2.4g daily). However, naproxen (1g daily) is associated with a lower thrombotic risk; and low dose ibuprofen (<1.2g daily) had not been associated with an increased risk of MI (5).

Thus, healthcare professionals should remember that diclofenac and selective COX-2 inhibitors are not suitable for patients with ischaemic heart diseases, and should be cautious with NSAID use in patients with renal impairment.

Lastly, the table below shows the drug classification of various NSAIDs in Malaysia in accordance to the Formulari Ubat Kementerian Kesihatan Malaysia (dated March 2016) to help those working in the public sector to prescribe and dispense NSAID accordingly.

Generic Name               Category
Celecoxib                        A or A*
Diclofenac                      B (tablet), A (gel & suppository)
Etoricoxib                       A*
Ibuprofen                       B
Indomethacin                 B
Meloxicam                      A/KK
Mefenamic Acid             B
Naproxen                       A or A/KK

Reference:
1. Brody H, Light DW. The inverse benefit law: How drug marketing undermines patient safety and public health. Am J Public Health. 2011;101(3):399–404.
2. Ong CKS, Lirk P, Tan CH, Seymour RA. An evidence-based update on nonsteroidal anti-inflammatory drugs. Clin Med Res. 2007;5(1):19–34.
3. Peterson K, McDonagh M, Thakurta S, Dana T, Roberts C, Chou R, et al. Drug Class Review: Nonsteroidal Antiinflammatory Drugs (NSAIDs). 2010;(November):72.
4. Richards D. Table 1: The Oxford Pain Group League table of analgesic efficacy [Internet]. Nature. 2004 [cited 2016 Jul 11]. Available from: http://www.nature.com/ebd/journal/v5/n1/fig_tab/6400237t1.html
5. Is the most suitable NSAID being used? Pharm J. 2014;292(7794):84.

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