New Rheumatoid Arthritis Drug Performs

Tofacitinib for rheumatoid arthritis showed improvement in symptoms but had side effects

(RxWiki News) Painful swollen joints are familiar to those with rheumatoid arthritis. But patients may have another option if they don't respond well to typically used medications.

A recent industry-funded study found that combining a new drug called tofacitinib with an existing prescription drug improved symptoms in those with rheumatoid arthritis. Rheumatoid arthritis is a condition that involves inflammation, pain and swelling in the joints.

Tofacitinib goes by the brand name Xeljanz and was approved by the FDA for rheumatoid arthritis in November of 2012. The drug carries a risk of serious side effects, including pneumonia, cancer and infections.

"Ask your doctor about rheumatoid arthritis treatments."

The study, led by Désirée van der Heijde, MD PhD, of Leiden University Medical Center in The Netherlands, is a two-year phase III, randomized, double-blind, placebo-controlled study. These results included the mid-study reports after one year.

A total of 797 adults with rheumatoid arthritis were randomly assigned to receive one of four treatments.

The adults were an average age of 53 and the majority (85 percent) were female. On average, the participants had suffered from rheumatoid arthritis for about nine years.

One group of 321 received 5 mg of tofacitinib twice daily, and one group of 316 received 10 mg of tofacitinib twice daily.

In the other two groups, 81 participants received 5 mg of a placebo (fake pill) twice daily, and 79 participants received 10 mg of a placebo twice daily.

Meanwhile, all the participants also received methotrexate at the same time as the tofacitinib or placebo. Methotrexate is a medication already used to treat rheumatoid arthritis.

After three months, any patients who were receiving the placebo and did not experience at least a 20 percent improvement in their swollen joints were then switched to receiving tofacitinib instead of the placebo.

The researchers said they made this switch for ethical reasons: if the participant was experiencing pain that might be helped by the tofacitinib, it would be unethical to withhold it from them.

After six months, all the patients who were taking placebos then began receiving tofacitinib instead.

The researchers compared the change in the participants' ACR20 score. ACR refers to the American College of Rheumatology, and the score is used to measure what percentage of change patients experience in rheumatoid arthritis symptoms.

At six months, 52 percent of those taking 5 mg of tofacitinib and 62 percent of those taking 10 mg of tofacitinib experienced at least 20 percent improvement in their symptoms. Meanwhile, only 25 percent of those taking the placebo experienced at least 20 percent improvement in their symptoms.

The improvements experienced by patients taking tofacitinib included less narrowing in their joint spaces and less continuing joint erosion than participants who received the placebo.

The difference was large enough to be significant with 10 mg of tofacitinib but not as much with 5 mg of tofacitinib.

The researchers concluded that their analysis "demonstrate[d] that tofacitinib inhibits progression of structural damage and improves rheumatoid arthritis activity in patients with rheumatoid arthritis on methotrexate."

The side effects reported during the first three months of the study were similar in both groups of participants: about 49 percent of those taking 5 mg of tofacitinib, 54 percent of those taking 10 mg of tofacitinib and 46 percent of those taking the placebo.

The most common adverse events reported were infections, gastrointestinal disorders and abnormal lab results, which resulted in the need for intervention (diagnostic treatment).

Over one year, approximately 3.68 out of 100 patients taking a placebo would be expected to experience a serious adverse event. The rate among those taking 5 mg of tofacitinib would be about 4.17 out of 100 patients over a year and, for 10 mg of tofacitinib, about 2.32 out of 100 patients over a year.

Six patients in the study died. Four were in the tofacitinib 5 mg group: one developed acute respiratory distress syndrome and viral pneumonia, one developed metastatic lung cancer and two developed pneumonia.

One patient receiving the placebo developed acute renal failure and died of a heart attack, and one patient taking 10 mg of tofacitinib died of aspiration (inhaling a foreign object).

"All deaths were attributed to the study drug (including the placebo-treated patient who died) by the investigator," the researchers wrote. Additionally, six patients receiving tofacitinib had non-fatal heart problems, and nine patients were diagnosed with a cancer.

Tofacitinib works by blocking an enzyme called Janus kinase 3, which then reduces inflammation caused by the body's immune system. Since rheumatoid arthritis is an autoimmune disease, that means the body is essentially mistaking parts of itself for a disease and attacking itself.

The study was published January 24 in the journal Arthritis and Rheumatism. The research was funded by Pfizer Inc. Six authors reported receiving financial compensation as research funding, honoraria or speakers' fees from Pfizer Inc., and eight authors were Pfizer employees who own stock or stock options in Pfizer. Five authors had no disclosures.

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Review Date: 
January 23, 2013