(RxWiki News) Although there are many different types of medications for rheumatoid arthritis, some patients don’t respond to treatment and physicians are still looking for safer and more effective alternatives. One of these alternatives may be tofacitinib (Xeljanz).
Tofacitinib is an FDA-approved oral antirheumatic medication created by Pfizer. Controversy on the use of tofacitinib was raised last April when it didn't get approved in Europe, with regulators saying that the benefits of the medication did not outweigh the serious concerns about safety.
"Ask a rheumatologist about new RA medications."
This large clinical trial was led by John Bradley, MD, the Director of Inflammation at Pfizer Global Research and Development, to investigate the efficacy and safety of tofacitinib when given to patients in combination with other antirheumatic medications. This trial used data on 795 participants from 19 countries and was supported by Pfizer Inc.
The participants were adults, over 18 years of age, diagnosed with rheumatoid arthritis who did not respond well to treatment with disease modifying medications for rheumamtoid arthritis (DMARDs).
The participants were randomly assigned to one of four treatment groups. The treatments given to each group included the following:
- 5 milligrams of tofacitinib twice daily for six months
- 10 milligrams of tofacitinib twice daily for six months
- Placebo (fake medicine) for three or six months, and then 5 milligrams of tofacitinib twice daily for six months
- Placebo for three or six months, and then 10 milligrams of tofacitinib twice daily for six months
Participants in each group were screened for improvement. This was a double-blind trial, meaning that neither the participants nor the doctors who evaluated the participants knew which treatment was given to each person.
Participants in this study had previously taken other antirheumatic medications when they were enrolled in this trial. If the medication that the participant was taking was a non-biological DMARD, they were able to continue taking the medication at regulated doses in combination with tofacitinib. Most of the participants in this study (79 percent) were using methotrexate.
Improvement among the participants was measured and compared using standard tests commonly used by rheumatologists to assess the condition of the joints.
The main tests used were the 20-percent improvement in American College of Rheumatology criteria (ACR20), Health Assessment Questionnaire Disability Index (HAQ-DI), and Disease Activity Score for 28-joint counts (DAS-28).
ACR criteria measure improvement in the number of tender or swollen joints and five other factors of rheumatoid arthritis. Achieving ACR20 means that a patient has had 20 percent improvement in tender or swollen joint counts and 20 percent improvement in three of the five other factors.
The HAQ-DI test measures disability. The patient reports how difficult it is to perform common daily tasks and a disability index is calculated.
The DAS-28 test classifies the disease as active, controlled or in remission (period when disease is inactive) according to a calculated score. It takes into consideration the number of tender or swollen joints, markers of inflammation in the blood and the patient’s physical health. Patients with a score less than 2.6 are considered in remission.
In this study, the researchers found that more participants achieved the ACR20 criteria in the groups taking tofacitinib (21.2 percent in the 5-milligram dose group and 25.8 percent in the 10-milligram dose group) compared with the placebo groups (no tofacitinib).
Participants in the tofacitinib groups also had a lower disability index (0.28 units for the 5-milligram dose group and 0.37 units for the 10-milligram dose group) than participants in the placebo group.
And more patients achieved the DAS-28 criteria for remission in the tofacitinib groups (5.8 percent of the 5-milligram dose group and 9.9 percent of the 10-milligram dose group) than participants in the placebo group.
In summary, participants who were taking tofacitinib performed better on the three tests than participants taking a placebo.
As usually happens with the use of immunosuppressant medications, tofacitinib may put patients at risk for other health problems.
The major side effects of tofacitinib include infections, cardiovascular issues, abnormal blood parameters, cancer and stomach ulcers.
In this study, two cases of tuberculosis, two cases of other infections, three cardiovascular events and four deaths occurred in patients who were taking tofacitinib.
More trials are scheduled to further investigate the efficacy and safety of tofacitinib, but so far tofacitinib has showed positive results in the treatment of rheumatoid arthritis.
The cost for a 30-day supply of 5-milligram tofacitinib tablets is estimated to be $2,180.
Steve Leuk, PharmaD, president and owner of AudibleRX, commented that the article describes an optimistic scenario, explaining how Tofacitinib increased patient outcome scores greater than 20%. “The study seems appropriate and on initial evaluation and individual may have high hopes for a new treatment of their RA. However, the side effect data and the reasons why tofacitinib wasn’t approved in Europe should be looked further in detail”, he said.
This study was published on August 20 in the Annals of Internal Medicine and was funded by Pfizer. Some of the authors are employed by Pfizer and others have received research support from Pfizer.