It results in significant morbidity (disability and crippling) and mortality (death). Nearly 80% of patients with RA are disabled after 20 years and life expectancy is reduced by between 3 to 18 years. RA patients can suffer from chronic pain, stiffness, functional impairment, and irreversible joint damage. They often require aggressive long-term therapy. RA is a disease in which responses to treatment can vary considerably from one patient to the next.

RA is a complex disease consisting of a series of cascading events involving immune cells that produce proinflammatory cytokines which are chemical messengers that amplify inflammation. Examples include such as tumor necrosis factor-alpha (TNF-α), interleukins, and others. Treatments that have been developed recently have been aimed at these proinflammatory cytokines.

Despite fantastic therapeutic advances with biologic agents, roughly 30% of patients fail to respond adequately. This article will discuss the decision making involved in deciding when a patient is not responding sufficiently to therapy.

There is no universally accepted definition of an "inadequate response". A rule of thumb is that a treatment regimen should be tried for at least 2-3 months before deciding that it is not effective in controlling disease activity.

The measurement scales that are used in clinical trials to assess response include a patient's subjective sense of where their disease is (patient global response), the doctor's impression (physician global response), the counting up of tender and swollen joints, and an assessment of the patient's ability to perform activities of daily living (Health Assessment Questionnaire [HAQ]). Blood tests like the erythrocyte sedimentation rate or C-reactive protein, and imaging techniques such as x-ray or magnetic resonance imaging.

In real life practice, a combination of the patient's response, the physician's response, and some objective measure such as ultrasound or magnetic resonance imaging or x-ray are used. These measurements are also accompanied by evaluation of blood tests such as the erythrocyte sedimentation rate (ESR) or C-reactive protein.

If, after 2-3 months on a drug, the patient has not achieved the desired response (eg, reduction in signs and/or symptoms of RA, improvement in tender and/or swollen joint count, lower HAQ score), or an initially good response decreases over this time period, the patient is said to have had an inadequate response.

Since there is no universally accepted definition of inadequate response, it is likely to be different in each patient. An inadequate response, then, could be defined as any response that does not lead to the degree of clinical improvement which is acceptable to both the patient and the physician.

So? just as the processes at the cellular level that cause the disease are complicated, so are the measures that determine whether a patient is truly improving.

Defining an ?adequate response?, then, requires evaluation of several clinical (history, physical exam, blood tests), structural (ie., imaging), and functional parameters (what's the patient's ability to perform the activities of daily living).

Here, it is the art of medicine that is most important. The physician-patient relationship is key to making treatment decisions.