Drug Discontinuations Rampant in Rheumatoid Arthritis

Alice Goodman

June 15, 2013

MADRID — Up to one third of patients with rheumatoid arthritis discontinue or change therapy in the first year of treatment, and that rises to 50% in the second year, according to a new study.

"Despite the availability of multiple therapies for rheumatoid arthritis in the United States, there is a high rate of discontinuation or change in therapy. We think this may be because patients have high expectations, but none of the therapies we have is a cure. I have to infer that patients' expectations are not being met, but I can't delve further from these data," said lead investigator Vibeke Strand, MD, from Stanford University in California.

Dr. Strand presented the results during a news conference here at the European League Against Rheumatism (EULAR) Congress 2013.

She reported that, on average, patients treated with tumor necrosis factor (TNF) inhibitors remained on therapy about 6 months longer than those treated with other biologic disease-modifying anti-rheumatic drugs (DMARDs). Lack of perceived efficacy was the most common reason for discontinuation or a change of therapy.

The researchers used data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry to evaluate the use of biologic therapies.

They identified 6209 patients who were older than 18 years and older than 16 years at the onset of rheumatoid arthritis and had more than 6 months of follow-up after initiation of first or subsequent biologic therapy.

Of this cohort, 5010 patients (80.7%) were being treated with a TNF inhibitor and 1199 (19.3%) were being treated with other biologic DMARDs. Overall, 2693 patients (43.4%) were biologic-naïve.

At baseline, the median duration of rheumatoid arthritis was 10.7 years, 26.1% of patients had high disease activity, 31% were taking prednisone, 67% were taking methotrexate, and 11% were taking leflunomide.

For the 3584 patients who discontinued or changed therapy, the reasons were similar in patients taking TNF inhibitors and those taking other biologic DMARDs.

Table. Reasons for Discontinuation or Change of Therapy

Reason Percent
Lack of efficacy 36
Safety concerns 20
Physician preference 27
Patient preference 18
Access to treatment 9


Median time to discontinuation was longer with TNF inhibitors than with anti-TNF inhibitors (26.5 vs 20.0 months).

On multivariate analysis, the strongest predictors of discontinuation or change of therapy were high disease activity, patient-reported depression, and more recent initiation of therapy.

"These are expensive drugs, costing €10,000 [~US$13,315] per year for each patient. We have to learn to stratify patients so we know who to give these drugs to," said Christopher Buckley, MBBS, PhD, from the University of Birmingham in the United Kingdom, who moderated the news conference. "In the era of personalized medicine, we need to select the right patient for the right therapy, as is done in breast cancer and other types of cancer."

"What you put in determines what you get out. The wrong match of drug to patient will lead to earlier discontinuation," Dr. Buckley told Medscape Medical News. "If the patient's expectations are not met, that is another nail in the coffin."

For rheumatoid arthritis, treatment decisions are typically based on the presence of rheumatoid factor, "which is crazy," Dr. Buckley said. "Physicians order drugs according to when they are launched; there is no science behind this."

A rational approach would be to determine which patients respond to an anti-interleukin-6 drug such as tocilizumab, a TNF inhibitor such as adalimumab, etanercept, or infliximab, an anti-interleukin-1 drug such as canakinumab, or a CTLA-4 inhibitor such as abatacept, he said.

"We need to stop random assignment for anti–rheumatoid arthritis drugs," he said.

Dr. Strand said she agrees with Dr. Buckley, but added that this is not happening in the United States, and there are currently no markers for these decisions. "We have nothing to guide us."

Dr. Strand is a consultant for CORRONA. Dr. Buckley has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2013. Abstract OP0064. Presented June 13, 2013.


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