Addiction is Only One Concern for RA Patients on Opioids


For rheumatology patients, opioids have more immediate risks than addiction, says the University of Michigan's Daniel Clauw, M.D., in an interview with Rheumatology Network.

With opioid addiction and overdose on the rise in the United States, physicians are caught between the need to help patients control pain and the duty to protect them from the dangers of addiction.

As some doctors call for education on proper prescription of opioid pain medications, others advocate for firm regulations on these drugs. Meanwhile, evidence continues to accumulate that for rheumatoid arthritis patients, exposure to opioid painkillers can raise the risk of bone fracture.

As U.S. heroin use is up across all income levels and most age groups, according to the Centers for Disease Control and Prevention in Atlanta. Rates of heroin overdose deaths have quadrupled since 2002. The strongest risk factor for heroin addiction, according to the agency, is a previous addiction to prescription opioids.

Already, the U.S. Drug Enforcement Agency has reclassified hydrocodone from a schedule III to a schedule II drug, tightening the regulations around its use. A study published January 25 in the journal JAMA Internal Medicine found that in the year after the rescheduling, prescriptions for hydrocodone combination agents dropped by 26.3 million (a 22 percent decline), and prescriptions for hydrocodone combination tablets went down by 1.1 billion (16 percent).

Not everyone agrees that regulatory changes are the answer. Daniel Alford, M.D., M.P.H., a professor of medicine at Boston University, wrote in the New England Journal of Medicine in January that "blunt approaches" such as caps on prescriptions will leave patients who could potentially benefit from opioids out in the cold. Alford argues for physician education - perhaps even mandatory education linked to medical licensure - to solve the opioid crisis. Currently, the Food and Drug Administration offers voluntary education through its Risk Evaluation and Mitigation Strategy (REMS).

Meanwhile, there is mounting evidence that for rheumatology patients, opioids have more immediate risks than addiction. A population-based, nested case-control study published in January in the journal Arthritis & Rheumatology found that current opioid exposure increased the risk of non-vertebral fracture in patients with rheumatoid arthritis.

Researchers used administrative databases to gather cases of nonvertebral fractures in rheumatoid arthritis patients in Quebec between 1997 to 2012. These cases were then matched with controls on age, sex and date of rheumatoid arthritis diagnosis. Forty-two percent of the 1,723 cases and 23 percent of 8,046 controls had been exposed to opioids. The researchers indexed previous opioid use to the date of fracture for the cases.

Cumulative use was associated with the risk of fracture (1-20 days odds ratio: 11.49 (95% CI, 8.81-14.99); 21-155 days OR: 1.75 (95% CI, 1.31-2.33); 156-355 OR 1.54 (95% CI, 1.17-2.04); 356 or more days OR 1.73 (95% CI, 1.31-2.30).

The highest risk for fracture was within the first week of opioid use, followed by days 8 to 20, the researchers reported. Thus, it seems likely that opioids increase the risk of fracture by increasing the risk of falls, they wrote.

To better understand the use of opioids in rheumatoid arthritis, Rheumatology Network spoke with Daniel Clauw,  M.D., a professor of anesthesiology, medicine and psychiatry at the University of Michigan who has been outspoken about the risks of  opioids in treating chronic pain. 

1. What are the potential benefits of prescribing opioid drugs to rheumatoid arthritis patients? [[{"type":"media","view_mode":"media_crop","fid":"45885","attributes":{"alt":"Daniel Clauw, M.D.","class":"media-image media-image-right","id":"media_crop_5408851238898","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5280","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"Daniel Clauw, M.D.","typeof":"foaf:Image"}}]]

Opioids should always be considered the "last resort" for treating pain associated with rheumatoid arthritis. First, the inflammation underlying RA should be aggressively treated. Then, any number of drug- and non-drug therapies should be tried before opioids. Most physicians are aware of the drug options but might not be as aware of all of the non-drug therapies that can be extremely effective in treating pain, including simple things such as exercise (using regions of the body not affected by RA), better quality sleep, etc. 

2. What are the risks? 

Opioids have a tremendous number of side effects, with the most serious of course being death.  Last year in the U.S., approximately 25,000 individuals died of opioid overdose, about two-thirds of which were from prescription opioids (the remainder were from heroin). Opioids can also worsen pain when taken for long periods of time, especially at high doses.

3. How effective are opioids for chronic pain issues, and are there any good alternative treatments? 

Most studies show that opioids are not very effective (or not effective at all) for treating chronic pain. Individuals often will get initial relief from an opioids (opioids work well to treat acute pain) but this effect often seems to wane over time. It had previously been thought that if you continued to raise the dose you could continue to get an analgesic effect, but these higher doses of opioids are the doses that are particularly problematic with regards to side effects.   

3. Multiple studies, including the latest cited above, have found increased fracture risk for RA patients exposed to opioids. Why might this risk occur, and is there any way to mitigate it?  

There may be many reasons but the primary one is that people are much more likely to fall when they are taking opioids. Chronic opioid users are often literally in a "fog" from their opioids and are unaware of how much opioids are clouding their thinking, slowing their movements. 

4. Is opioid addiction/misuse a major problem in rheumatoid arthritis patients?

Individuals with RA are not any less likely to have misuse, addiction or other problems than individuals without RA.

5. What are the limitations to the current REMS strategies for dealing with opioid prescriptions? 

The current REMS strategies are somewhat misguided because they assume that most individuals newly starting opioids are purposefully started on an opioid for chronic pain by their physician. The problem is that at present, most U.S. physicians will not newly start an opioid for chronic pain, and instead individuals are more likely to get their first exposure to an opioid after a surgical procedure or ER visit.  Once they begin taking them and like them (which can be because they treat pain but more often is because they dull the person to their pain or make them feel less depressed) then the person’s treating physician is in a conundrum - do I continue prescribing even though I feel that this is a bad idea, or do I tell my patient I am unwilling to continue prescribing this class of drugs?    

6. How should the medical profession as a whole deal with the problem of opioid misuse? Voluntary education for physicians, mandatory education, labeling changes, caps on dosages, etc?  

All of the above. This is a very dangerous class of drugs. I feel that there are two areas that require specific attention. First, physicians should not give large doses of opioids for acute pain (e.g. following surgical procedures).  These end up causing many of our current problems because many individuals then continue taking these drugs for their chronic pain. 

The second related problem is that these large prescriptions often sit in a medicine cabinet and are taken by friends and family, who then become addicted to opioids - and move to heroin because it is the cheapest opioid on the street. Patients should immediately discard any unused prescriptions of opioids. If you would not keep a loaded gun in your medicine cabinet, then do not leave unused opioids in your medicine cabinet - they are at least as dangerous. 

7. Finally, how should individual rheumatologists weigh the question of prescribing opioids for rheumatoid arthritis patients at this time?  

There are very few patients in whom the benefit of an opioid exceeds the risk.



1. Jones CM, Lurie PG, Throckmorton DC.

"Effect of US Drug Enforcement Administration’s Rescheduling of Hydrocodone Combination Analgesic Products on Opioid Analgesic Prescribing,"


JAMA Intern Med. 

Published online January 25, 2016. doi:10.1001/jamainternmed.2015.7799 2. Alford, Daniel P.

"Opioid Prescribing for Chronic Pain - Achieving the Right Balance through Education," 

N Engl J Med 

2016; 374:301-303. January 28, 2016. doi: 10.1056/NEJMp1512932. 3. Acurcio, F. A., Moura, C. S., Bernatsky, S., Bessette, L. and Rahme, E. (2016),

"Opioid Use and Risk of Nonvertebral Fractures in Adults With Rheumatoid Arthritis: A Nested Case–Control Study Using Administrative Databases,"

Arthritis & Rheumatology, 68: 83–91. doi: 




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