Disclosures: Miller reports no relevant financial relationships.
August 14, 2020
5 min read

‘Room for improvement’: Treating ankylosing spondylitis

Disclosures: Miller reports no relevant financial relationships.
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Ankylosing spondylitis presents significant challenges in pain management and remains a controversial topic with limited data for efficacy.

Current guidelines for rheumatologists suggest biologic tumor necrosis factor and interleukin 17 (IL-17) inhibitors, disease-modifying antirheumatic drugs (DMARDs) like sulfasalazine, and antirheumatic treatments with NSAIDs to relieve pain and stiffness. But those guidelines neglect to mention opioids for chronic pain commonly experienced in ankylosing spondylitis (AS), despite patient use of 23.5% to 76%.

According to John Miller, MD, instructor of medicine from Johns Hopkins, opioid management presents unique challenges for this complicated disease. He also noted alternative treatments being explored in AS to alleviate challenges from opioids, including mental health awareness, integrated approaches and individualized treatment.

“There is still a subset of patients who are returning to opiates, but ... that number isn’t increasing. It’s decreasing, because the opiate issues have taken a national spotlight and most young people are doing everything possible to avoid it,” Miller said.


Opioid use is a hotly debated topic in treatment. Patients who cannot afford or do not have access to biologics may require opioids for less expensive, rapid pain relief, but may find obtaining a prescription a challenge in the current medical climate after the opioid epidemics in the late 1990s, 2010 and 2013.

“There are some patients who need opiates, and regulations have made it very difficult for those patients to get them,” Miller said. “Physicians were prescribing opiates much too frequently in the past, but there are some people who absolutely need them, and feel villainized because that pendulum has swung too far the other way.”

Another challenge in AS is depression, which affects a third of patients, and correlated with more opioid use in a randomized controlled trial. According to another study, higher levels of depression correlated with more severe disease activity and functional impairment.

John Miller
John Miller, MD

Stress and depression produce adverse effects on overall health, and can aggravate symptoms, the ability to manage pain and may influence opioid use.

Patients using opioids had worse median self-assessment of health, higher frequency of depression and were 60% more likely to become depressed compared with case controls in the general population, according to a study published in The Journal of Rheumatology. The study showed a correlation between AS disease activity, depression and opioid use, with patients reporting high levels of disease activity, functionality and pain. Inquiring about a patient’s psychological health is a weak point in patient–physician communications and needs improvement, Miller said.


“[AS] can be debilitating, and we do a terrible job at addressing the depression that comes from it. We’re not good at detecting or asking, and sometimes we'll take the face value, ‘I'm okay’ and move on. We’re probably under reporting and under appreciating,” Miller said. “Compared to 30 years ago, management has changed dramatically with biologic medicines, but there’s a lot of room for improvement because there are still so many patients with pain, stiffness, fatigue and depression.”

Although patients with higher disease activity and opioid use report higher levels of depression and anxiety, it is difficult to determine if the source is from active disease and inflammation or typical negative effects of AS (eg, extended periods of sleeplessness, chronic pain) and drug resistance. Patients with pain hypersensitization are going to have higher scores, Miller said, and these may not always correlate with disease activity.

Miller stressed that it’s imperative to holistically assess patient needs and stage of disease before prescribing or renewing an opiate prescription.

“Most of our patients are young, and ankylosing spondylitis is a very chronic disease. If you’re starting opiates at a young age, you’re almost committing someone to that for the rest of their life. You want to be as judicious as possible to try everything else possible to prevent that, because with long term opiate use patients tend to need higher doses with time,” Miller said. “It’s a vicious feedback circle. When you’re starting, and looking at a 20- or 30-year-old, you want to do everything possible [in the present] not to commit that patient to long term therapy.”

Alternative treatments, physical therapy

Treatment in the form of physical and alternative therapies have been on the rise in AS. Among alternatives for opioids in pain relief is medical cannabis, which Miller noted is gaining popularity among younger patients leery of opioid addiction. However, patients and physicians must be aware of the limitations and lack of data for medical cannabis use in AS.

“Compared to use of opioids, it’s probably a safer alternative, but there are no data yet,” Miller said. “As an adjunct, it’s a reasonable option, especially compared to opiates, as long as it doesn’t replace our ‘bread and butter’ medicines. Medical marijuana may make you feel better, but it’s not clear that it changes disease activity or outcomes.”

Drug-free treatments for AS include exercise, posture practices and physical therapy to relieve disease symptoms and decrease pain. Physical therapy has been found to be highly effective in improving patient mobility and general quality of life as well as posture, fitness and mood.


“Physical therapy is very helpful from a pain stiffness fatigue standpoint, and if you're comparing NSAIDS and physical therapy to opiates, NSAIDS and physical therapy are more effective at decreasing pain,” Miller told Healio.

He recommended using an integrated, multi-team approach to achieve best patient treatment. “We frequently work with pain management groups because it has become so nuanced and cumbersome in terms of follow-up appointments that we offer work together with pain management groups. Having an anesthesiologist onboard to say ‘Here are some adjunct therapies’ or ‘Here are local therapies to minimize this symptom’ goes a long way. Collaboration with opinion can be very helpful.”

Future of AS

Though AS is a complicated chronic disease, there are strides being made for treatment. “The field is taking a 180-turn in terms of approach. Cymbalta [duloxetine, Eli Lilly], gabapentin, injection, physical therapy, stretching exercises, weight loss — a multi-targeted approach has changed how we deal with pain,” Miller told Healio.

A novel drug possibility in the pipeline is low-dose naltrexone (LDN), which has demonstrated a reduction in symptom severity in other inflammatory diseases like fibromyalgia, Crohn’s disease and multiple sclerosis.

Anti-opioid agonist LDN has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease and multiple sclerosis, and may show some promise in AS treatment as an anti-inflammatory for chronic pain.

Similar to opioids and NSAIDS, LDN is inexpensive oral therapy and functions, and has shown few adverse side effects, though there are large gaps in data.

“A low-dose naltrexone is something that many are interested in, but that too needs more data. There are some who swear it helps with pain, though it's not specific to ankylosing spondylitis,” Miller said.

Miller reports no relevant financial relationships.


  • Toljan K, et al. Med Sci (Basel). 2018;doi:10.3390/medsci6040082.
  • Younger J, et al. Clin Rheumatol. 2014;doi:10.1007/s10067-014-2517-2.
  • Zhao S, et al. ArthritisTher. 2018;doi:10.1186/s13075-018-1644-6