Use of Disease‐Modifying Antirheumatic Drugs in Rheumatoid Arthritis: Supporting Shared Decision‐Making Between Patients With Cancer and Clinicians

Newer disease‐modifying antirheumatic drugs (DMARDs) hold promise for improving quality of life and reducing disability related to rheumatoid arthritis (RA) (1). However, enthusiasm for the use of these agents has been tempered by concern for a potentially increased risk of malignancy (2), a particular concern for the substantial number of people with RA who have or are at an increased risk for developing cancer (3).

A US Food and Drug Administration (FDA) black box warning attached to these agents cautions of the risk of incident lymphoma associated with tumor necrosis factor inhibitors (TNFi). However, this is based on the results of older studies (4). More recent work, including meta‐analyses of multiple large population‐based studies of the use of TNFi in patients with RA, has failed to find an increased risk of lymphoma among those receiving these agents (5, 6). Nonetheless, the FDA warning undoubtedly continues to raise concern in the minds of patients and clinicians regarding the safety of these agents.

In this context, how to treat patients with RA diagnosed with an active or recent (within 5 years of diagnosis) cancer presents a challenging clinical conundrum. Theoretical concern that biologic and other immunosuppressive agents may increase susceptibility to malignancy may make clinicians reluctant to use these therapies in patients with an active or recent cancer. Newer studies, though limited, challenge these concerns (7, 8, 9, 10). In one of the largest studies to date on the risk of recurrent cancer, Dreyer et al assessed the risk of mortality in patients with RA and a history of a primary cancer using the Danish biological and cancer registries (7). These authors found that biologic DMARDs did not increase the risk of a second cancer diagnosis; further, the number of deaths observed was relatively small. The study lacked information on the cause of death, so it could not evaluate cancer‐specific mortality. Several other studies examining the relationship between DMARD use and the risk of recurrent cancer have not reported significant harmful impacts, although they were limited because of small sample sizes, and a majority of patients included in these studies were long‐term cancer survivors (10). Therefore, the data on how use of DMARDs impacts survival in patients with active or recently diagnosed cancer are sparse. Also, how the absence of high‐quality evidence, as well as the black box warning suggesting potential harm with TNFi, has shaped the care of patients with RA and concomitant (or history of or high risk for) cancer is not known.

Recommendations from an international task force in rheumatology suggest that “the treatment of rheumatoid arthritis must be based on a shared decision between patient and rheumatologist” (11), and this approach is specifically recommended for patients with RA who have a current or prior history of cancer who are contemplating use of these agents (12). Shared decision‐making (SDM) is a process whereby both the patient and the clinician consider the best available evidence of risks and benefits across all available treatment options in the context of each patient's unique circumstances, values, goals, beliefs, expectations, and preferences when making medical decisions (13). Given that few data exist to guide SDM in this context, there is clearly a critical need for more rigorous research on the benefits and harms of DMARDs in people with RA who have an active or recent cancer diagnosis. Given the limited data and substantial uncertainty about the benefits and harms of these agents in patients with a current or prior diagnosis of cancer, more work is needed to guide the SDM process and facilitate conversations between patients and rheumatologists about RA treatment in this context.

To illustrate how a well‐considered approach to SDM might look in this setting, let's consider the situation of Mrs. Doe, a 65‐year‐old woman who has lived with RA for the past 8 years. Her RA has been well controlled on methotrexate at 20 mg weekly and etanercept at 50 mg weekly for the last several years. She was recently diagnosed with metastatic melanoma and will be meeting with her oncologist to discuss management of melanoma. Her other comorbidities are hypertension and diabetes. While seeing the rheumatologist in follow‐up today, she asks about the benefits and harms of continuing her current RA therapies, especially in the context of a new diagnosis of melanoma. She also shares that she is especially worried about her ability to continue to babysit her granddaughters twice a week, which is an activity that is a big priority for her and gives her life meaning.

The lack of high‐quality evidence to inform answers to this patient's questions and the different burden and safety profiles of her RA medications in the context of a new diagnosis of cancer pose a substantial challenge. In this context, Mrs. Doe's rheumatologist should be transparent about the limitations of available evidence and acknowledge the high degree of uncertainty about the potential benefits and harms of continuing to use a DMARD in this context, and any recommendations should reflect Mrs. Doe's own priorities and values.

Decision aids (DAs) are evidence‐based tools that can facilitate SDM. An example of a validated DA is the Diabetes Medication Choice DA (14). This tool helps support a meaningful discussion between patients and their clinicians when faced with a decision about starting a diabetes medication. The Diabetes Choice DA outlines the benefits (hemoglobin A1c reduction), harms (eg, hypoglycemia), convenience, and cost of each of the available alternatives (14). In a Cochrane review of 105 studies of DAs (that focused on 50 different decisions), patients using DAs felt more informed, had a better idea of what mattered most to them, and had more accurate expectations of the benefits and harms of different treatment options as compared with patients receiving usual care (15). To develop a similar, effective tool to foster SDM in the clinical scenario, better evidence is needed regarding the comparative safety of DMARDs in the setting of different types and stages of cancer as well as how to best facilitate communication not only between the patient–rheumatologist dyad but also with the treating oncologist.

A shared approach to decision‐making is especially important for adults with RA and an active or recent cancer diagnosis because many are older and have multiple chronic conditions. Not only are many of these patients typically excluded from randomized controlled clinical trials, but they also have multiple potentially competing health conditions and receive care from multiple providers (16). To date, very little is known about how to promote high‐quality SDM around use of DMARDs in patients with RA with cancer, including who should be involved, what resources might be helpful, what information patients and clinicians would find most useful, and how best to involve different specialists with relevant expertise in the SDM process (eg, rheumatologists and oncologists) (Figure 1). Although we know that uptake of SDM in RA is generally suboptimal (17, 18), little is known about the use of SDM when considering use of biologic agents for individuals with an active or recent history of cancer. More research is needed to generate evidence and identify priorities to support SDM and optimize the care of patients with RA and an active or recent cancer diagnosis.

Figure 1.

Conceptual framework outlining the complexity of shared decision‐making in the management of people with RA and cancer. RA, rheumatoid arthritis.

AUTHOR CONTRIBUTIONS

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published.

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