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.