patient care perspectives

Management of Unacceptable Pain or Refractory Pain in Patients Who Have Inadequate Responses to Disease-Modifying Antirheumatic Drugs

by Jeffrey R. Curtis, MD, MS, MPH


When assessing residual pain in patients with rheumatoid arthritis (RA), it is important to differentiate between symptoms due to RA and symptoms associated with other underlying comorbidities.

Expert Commentary

Jeffrey R. Curtis, MD, MS, MPH

Marguerite Jones Harbert-Gene V. Ball, MD Professor of Medicine
Co-Director, UAB Pharmacoepidemiology and Pharmacoeconomics Research (PEER) Unit
Division of Clinical Immunology and Rheumatology
University of Alabama at Birmingham
Birmingham, AL

“When patients rate their levels of pain, it is incredibly important to understand exactly what pain they are talking about. It is not always easy to disentangle why they hurt.”

Jeffrey R. Curtis, MD, MS, MPH

The topic of pain in patients with RA is intriguing and provocative because there is often an expectation that pain will improve after inflammation is controlled. This is often the case, and, on average, the patient’s global assessment of disease activity and the level of self-rated pain are highly correlated. However, some individuals report meaningful differences between them. In assessing disease activity, there can be patient-provider discordance, and this may occur in as many as one-third of cases. In one discordant scenario, a patient may report dissatisfaction with their symptom state, with high levels of residual pain, while their doctor believes that the RA is adequately controlled. One possibility is that patients self-assess signs and symptoms of other comorbidities and attribute them to their RA. It is also possible that individuals with RA can experience pain despite good disease control, as in long-standing disease when joint damage and/or osteoarthritis are present. Rheumatologists and other clinicians caring for patients with RA face a significant dilemma precisely because the options for treating pain remain problematic. There is a surprisingly high rate of chronic opioid use in patients with RA who are on biologics. In our analysis of a Medicare sample (mean age, 67 years), we found that approximately 40% of individuals with RA used an opioid regularly.

We cannot expect patients to differentiate pain due to RA from pain due to osteoarthritis, chronic low back pain, herniated disk, sciatica, or postherpetic neuralgia, to name a few. Thus, when patients rate their levels of pain, it is incredibly important to understand exactly what pain they are talking about. It is not always easy to disentangle why they hurt. When fatigue is introduced, you add another layer in that fatigue can amplify pain. Understanding the origin of the fatigue is likewise key. If the fatigue is due to RA, then the fatigue should improve as the RA is controlled; however, if the fatigue is due to another cause (eg, sleep apnea), then escalating the RA treatment will not help the fatigue at all.

The psychological aspects of pain and fatigue are also important. Some patients have much less emotional and psychological resilience to deal with pain and fatigue than others, and this impacts their ability to function. What some individuals tolerate may be completely devastating to others, and these differences in individual resilience may be influenced by social circumstances, coping skills, and a number of other factors.

Pain scales, such as those from the National Institutes of Health Patient-Reported Outcomes Measurement Information System, that measure how much pain interferes with the patient’s life and functioning, in addition to pain intensity, are very helpful. Wearable devices can also help to shed light on the role of sleep in patient-reported pain and fatigue. This is an exciting area and the wave of the future.


Amtmann D, Cook KF, Jensen MP, et al. Development of a PROMIS item bank to measure pain interference. Pain. 2010;150(1):173-182.

Bykerk V, Wei W, Boklage S, Kimura T, Fiore S, St John G. Impact of sarilumab on unacceptable pain and inflammation control in moderately-to-severely active rheumatoid arthritis (RA) patients in 3 phase 3 studies [abstract 1393]. Arthritis Rheumatol. 2019;71(suppl 10). Accessed January 4, 2020.

Curtis JR, Xie F, Smith C, et al. Changing trends in opioid use among patients with rheumatoid arthritis in the United States. Arthritis Rheumatol. 2017;69(9):1733-1740.

Duarte C, Santos E, Kristianslund E, et al. Inflammation but also pain and function, and psychological impact is related to non-acceptable status in patients with rheumatoid arthritis: a factorial analysis in 643 patients [abstract 477]. Arthritis Rheumatol. 2019;71(suppl 10). Accessed January 4, 2020.

Olofsson T, Wallman J, Jöud A, et al. Unacceptable, refractory pain despite inflammation control in early rheumatoid arthritis and its relation to treatment strategy: results from the randomised controlled SWEFOT trial [abstract OP0133]. Ann Rheum Dis. 2018;77(suppl 2):117.

Smolen JS, Strand V, Koenig AS, Szumski A, Kotak S, Jones TV. Discordance between patient and physician assessments of global disease activity in rheumatoid arthritis and association with work productivity. Arthritis Res Ther. 2016;18(1):114.

Tubach F, Ravaud P, Martin-Mola E, et al. Minimum clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: results from a prospective multinational study. Arthritis Care Res (Hoboken). 2012;64(11):1699-1707.

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