Rheumatology
Rheumatoid Arthritis
Clinical Impact of Non–Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis
Overview
By definition, non–disease-modifying antirheumatic drugs (non-DMARDs) are not disease modifying but can significantly impact the health and well-being of patients with rheumatoid arthritis (RA). Opioid analgesics and corticosteroids, in particular, are non-DMARDs that have the potential for overuse and/or inappropriate use in certain clinical scenarios involving patients with RA. Further, corticosteroids are included among the leading risk factors for complications such as severe infections and reduced quality of life. Opioid use has also been associated with increased risk for hospitalization related to serious infection. Our experts in the field discuss how non-DMARD therapies factor into the care of patients with RA.
Q: How do non-DMARD therapies currently factor into the treatment of patients with RA?
Vibeke Strand, MD, MACR, FACP
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“In some instances, we are treating 40 years of disease—or even more in patients who developed RA at a young age—and, so, the patient’s list of medications will reflect that.”
There is no question that we often have numerous comorbidities to manage in patients with RA, and this is especially true as disease duration increases. In some instances, we are treating 40 years of disease—or even more in patients who developed RA at a young age—and, so, the patient’s list of medications will reflect that.
John R. P. Tesser, MD
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“Rheumatologists are very well educated in this area and are prepared to anticipate the possibility of interactions with non-DMARD agents and to monitor patients accordingly.”
We all are aware of the potential problems affecting different systems that any of the drugs can cause. When you combine different drugs, you can get an additive effect in an individual patient on an organ system such as the liver. Rheumatologists are very well educated in this area and are prepared to anticipate the possibility of interactions with non-DMARD agents and to monitor patients accordingly.
Jonathan Kay, MD
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“Use of opioids should generally be avoided in patients with chronic inflammatory arthritis. These individuals have a chronic disease that will require treatment for years, and, if we treat pain with addictive medications instead of treating the underlying disease, then patients are likely to develop structural damage and may ultimately lose the analgesic effect of the opioid.”
The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) with methotrexate creates a potential interaction that prompts many unnecessary phone calls from pharmacies, which may result in unnecessary delays in filling prescriptions. This interaction tends not to be clinically significant, since we adjust methotrexate dosing in accordance with efficacy and toxicity.
Use of opioids should generally be avoided in patients with chronic inflammatory arthritis. These individuals have a chronic disease that will require treatment for years, and, if we treat pain with addictive medications instead of treating the underlying disease, then patients are likely to develop structural damage and may ultimately lose the analgesic effect of the opioid.
Statins should be prescribed for patients with hyperlipidemia who, because of their inflammatory arthritis, are at increased risk for cardiovascular disease. If treatment with an interleukin 6 (IL-6) inhibitor or a Janus kinase inhibitor increases serum lipid levels, initiation of statin therapy may be necessary. Since both statins and some drugs used to treat inflammatory arthritis may cause liver function abnormalities, liver function should be monitored regularly during treatment with these drugs.
Vibeke Strand, MD, MACR, FACP
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As Dr Kay mentioned, statin therapy or adjustments may be needed with IL-6 inhibition if there is a rapid reduction in C-reactive protein levels. However, these changes are relatively subtle and are fairly easy to monitor through measurement of high-density lipoprotein/low-density lipoprotein cholesterol levels. Regarding methotrexate and NSAIDs, we know the dose to be used for an NSAID and/or we decide on the methotrexate dose to be used based on our evaluation of the response, and we factor in other concerns. And we do not use cyclosporine any longer, which has a major drug-drug interaction with methotrexate. |
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Leonard H. Calabrese, DO
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I think that patients with RA generally have a very low risk of opioid addiction. In my experience, patients with opioid addiction problems tend to be the individuals who have problems with addiction in other areas. Patients with RA tend to be remarkably stoic. We are still sorting out the NSAID issues. The glucocorticoids are the other major “non-DMARD,” although they really are a DMARD, and they are included among the leading risk factors that lead to complications such as severe infections and reduced quality of life. |
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“The glucocorticoids are the other major ‘non-DMARD,’ although they really are a DMARD, and they are included among the leading risk factors that lead to complications such as severe infections and reduced quality of life.”
Vibeke Strand, MD, MACR, FACP
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I also agree that patients with RA have a very low risk of opioid addiction and that their judicious use may be helpful. By and large, the pain arises from inflammation so that we know we are not adequately controlling the underlying disease, and we need to address that. I am less in favor of glucocorticoids. I think that they are useful in the first 2 years of disease, when they have been shown to reduce progression of structural damage. They can be used on an intermittent basis for flares, but I would rather patients not use them on a chronic basis and instead use them only intermittently for flares. You have to be really careful about training a patient in the use of the low doses of corticosteroids for RA, so that they do not become tachyphylactic and do not require higher doses such that we cannot control their flares. Many patients with RA have the 5-mg dose of prednisone on hand at home that they take when they need to. I am not a huge advocate of dose packs because those doses can be fairly high, even if they are rapidly tapered. |
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John R. P. Tesser, MD
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I concur with all of my colleagues. I believe that the overarching principle here is to use DMARDs to optimal advantage for disease control and to eliminate the use of NSAIDs, steroids, and opioids. |
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Jonathan Kay, MD
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I try to use corticosteroids infrequently and judiciously in my patients. I often will prescribe a tapering course of corticosteroid initially to control disease activity rapidly, while waiting for DMARDs to exert their therapeutic effect. When necessary, I may prescribe a brief corticosteroid taper to treat an exacerbation of disease activity. |
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References
Colebatch AN, Marks JL, van der Heijde DM, Edwards CJ. Safety of nonsteroidal antiinflammatory drugs and/or paracetamol in people receiving methotrexate for inflammatory arthritis: a Cochrane systematic review. J Rheumatol Suppl. 2012;90:62-73.
Kavanaugh A, Wells AF. Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis. Rheumatology (Oxford). 2014;53(10):1742-1751.
Kern DM, Chang L, Sonawane K, et al. Treatment patterns of newly diagnosed rheumatoid arthritis patients from a commercially insured population. Rheumatol Ther. 2018 May 30. doi: 10.1007/s40744-018-0114-6. [Epub ahead of print]
Kim D, Cho SK, Park B, Jang EJ, Bae SC, Sung YK. Glucocorticoids are associated with an increased risk for vertebral fracture in patients with rheumatoid arthritis. J Rheumatol. 2018;45(5):612-620.
Konijn NPC, van Tuyl LHD, Boers M, et al. Similar efficacy and safety of initial COBRA-light and COBRA therapy in rheumatoid arthritis: 4-year results from the COBRA-light trial. Rheumatology (Oxford). 2017;56(9):1586-1596.
Ridker PM. From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res. 2016;118(1):145-156.
Wiese AD, Griffin MR, Stein CM, Mitchel EF Jr, Grijalva CG. Opioid analgesics and the risk of serious infections among patients with rheumatoid arthritis: a self-controlled case series study. Arthritis Rheumatol. 2016;68(2):323-331.
