Medication Non-Adherence by Rheumatology Patients & What Rheumatologists Can Do

Case Study

A 34-year-old woman presents to you for a first visit. She has a 10-year history of active, seropositive and erosive rheumatoid arthritis and she also struggles with hypertension and morbid obesity. Her weight decreased dramatically several years ago after a gastric bypass. She is a survivor of domestic violence, and she faces the challenges life throws at her with humor and grit. In the past, she had done well on methotrexate and infliximab, but has been off of all medications for a year since she lost her insurance.

You decide to restart the same medications, but you note both iron and B12 deficiency. You are worried about absorption of oral methotrexate. She expresses some reluctance and a fear of needles, but after a long discussion she agrees to try subcutaneous methotrexate. After three months on infliximab, she exhibits only mild improvement. At the end of a long follow-up visit to go over her exam and discuss options, she reveals that she has not been taking the methotrexate.

Scope of the Problem

Rheumatology has experienced a revolution in recent years with the introduction of biologic drugs that ameliorate or completely remit many of our complex illnesses. But medications work only if they are taken. Medication non-adherence is a common problem in patients with acute and chronic diseases. Only about 25% of medications are filled correctly, and 30% of new prescriptions are never filled.^1,2

Rheumatology patients exhibit similar behavior. Patients with osteoporosis take oral bisphosphonates correctly only 60% of the time. Patients do even worse with teriparatide, especially over the course of two years of treatment.³ Fewer than half of patients with gout are adherent to urate-lowering medication regimens.⁴ In rheumatoid arthritis, patients do a little better. Adherence rates range closer to 80% for methotrexate or other oral monotherapy. Adherence goes down with the increasing complexity of a medication regimen, and complex regimens are commonplace in our specialty.⁵ Data regarding adherence to self-injected anti-TNF therapy is more variable, but rates are probably not much better.⁶ Adherence to infliximab infusions is higher, closer to 90%, undoubtedly related to the necessity of administering it under observed conditions. As with oral disease-modifying antirheumatic drugs (DMARDs), adherence goes down with combination therapy. This is especially notable because we most frequently use anti-TNFs in combination with oral DMARDs.

Why Do We Care?

It’s intuitive that patients with poor adherence will have worse outcomes. Failing to take bisphosphonates is associated with increased risk of fracture. In RA, failure to take DMARDs brings a higher risk of flares, damage, and need for surgery. Non-adherence to urate-lowering therapies is associated with more tophaceous gout, as well as higher rates of absenteeism from work and reduced productivity.⁷ Non-adherence also has the potential to lead to inappropriate medication changes. Lack of efficacy and poor DAS scores may be misinterpreted as a drug failure when they are actually a consequence of non-adherence. This, in turn, has the potential to lead to increased cost and an increased number of prescribed medications.

Why Don’t Patients Just Take Their Medications?

Non-adherence is multifactorial and complex. Certain co-morbidities, such as cognitive impairment, depression and substance abuse, increase the risk. Patients with asymptomatic disease are also less likely to take medications consistently. Gout is a particular disease in which the patient might feel well between attacks and question why they are taking a daily medication. Many patients worry about the cost of medication. This becomes especially evident with expensive biologic drugs we prescribe. Even for an insured patient, a 20% co-pay on a $2,000/month drug might be unaffordable. As already noted, complex dosing schedules are another major issue. A preference for natural therapies may lead patients to avoid prescribed medications. For other patients, a fear of side effects outweighs the potential benefit of a drug.

In some cases, medications are perceived as being ineffective. Many RA medications take months to reach full efficacy. Patients in remission sometimes stop their medications. It’s incumbent on us to outline the time line for a sufficient trial of medication and to teach that remission is not synonymous with cure.

Initiation of urate-lowering therapy is another time that anticipatory counseling can make a difference: It may be hard to convince a patient who flares after starting allopurinol that this is a medicine that really treats gout! Preemptive discussion of the potential to have flares may prevent self-discontinuation of the medication.

Importantly, patients are less likely to take medications if they hold beliefs or have concerns that conflict with the provider’s beliefs and concerns. Factors that drive rheumatologists to change medication regimens in rheumatoid arthritis are what we expect—swollen joint counts, physician global assessment, worsening erosions and increased disease activity compared with the prior visit. In contrast, when patients were asked what may lead them to escalate care, they cite painful joint counts, current physical functioning, satisfaction with current DMARDs and trust in their rheumatologist.⁸ Exploration of patient values and preferences around illness and medication can help tease out if patients are likely to be taking a prescribed regimen.

What Can We Do about It?

Improving adherence in chronic disease is challenging. Interventions that have been studied and found helpful almost all require a substantial amount of effort and resources. These interventions have to be continued indefinitely, because there is no evidence that low adherence can be “cured.”⁹

One step that can be taken is to simplify dosage regimens when possible. Are there any medications that can be discontinued? Is a long-acting version available to decrease the dosing frequency?

Also, we should spend time on the front end to elicit patient concerns and make sure we are connected to the patient so they can share their fears and concerns.

Employing the teach-back method at the end of a visit is an excellent way to ensure patient understanding. One might say to the patient at the end of a visit, “What are you going to tell your spouse about our conversation and what medications you will be taking?” This technique can reveal important gaps in patient understanding.

Writing down the diagnosis highlights and medicine regimens may also improve education and retention.

Communication is at the heart of the adherence issue. The best predictor of adherence is the clinician–patient relationship. You need to understand the patient’s own belief about their illness. You need to show empathy by using good body language and by voicing concern about how the disease is affecting the patient.

The most important thing we can do as practitioners is to remember that non-adherence is a prevalent problem and to ask our patients if and how they are taking their medications. If answers are discordant from available pharmacy data, one needs to address the discrepancy.

It’s easy in clinic visits to focus on side effects and disease control, but asking more open-ended questions, such as, “Do you have any concerns about your medications?” or “What might get in the way of you taking this medication?” might give a patient space to share whatever problem they are having.

A shift in physician mentality from non-adherence to shared decision making can be helpful in improving adherence to medication and improving disease control.

Jennifer Stichman, MD, is an assistant professor of general internal medicine at Denver Health and the University of Colorado.
Dennis J. Boyle, MD, is an associate professor of medicine and rheumatology at Denver Health and the University of Colorado.

References

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2. Fischer MA, Stedman MR, Lii J, et al. Primary medication non-adherence: Analysis of 195,930 electronic prescriptions. J Gen Intern Med. 2010 Apr;25(4):284–290.
3. Foster SA, Foley KA, Meadows ES, et al. Adherence and persistence with teriparatide among patients with commercial, Medicare, and Medicaid insurance. Osteoporos Int. 2011 Feb;22(2):551–557.
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8. van Hulst LT, Kievit W, van Bommel R, et al. Rheumatoid arthritis patients and rheumatologists approach the decision to escalate care differently: Results of a maximum difference scaling experiment. Arthritis Care Res (Hoboken). 2011 Oct;63(10):1407–1414.
9. Haynes RB, Ackloo E, Sahota N, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD000011.