Biologics
Biologic therapies have been available for clinical use since 1998, Dr. Weinblatt said. A key concern with drugs that block tumor necrosis factor (TNF), or anti-TNF therapy, is the risk of flare after withdrawal.
Several studies show that patients taking a biologic and who do well for six to nine months but then abruptly stop treatment, the majority experience a disease flare. More concerning, in one study that looked at withdrawal specifically, 15% of patients were unable to get back to low disease activity after restarting therapy.2 Instead of abandoning treatment, it may be better to have patients who are doing well reduce their dose or extend the time between doses, Dr. Weinblatt said.
The risk of infection—in some cases, serious infections or hospitalization—with biologic therapy is well established. The use of corticosteroids—with or without anti-TNF therapy—is known to increase infection risk. For this reason, Dr. Weinblatt said, it’s important to get patients on as low a dose as possible of steroids or to get them off steroids all together.
Regarding the risk of major adverse cardiovascular events, a January 2020 study in Arthritis & Rheumatology concluded there was no increased risk among patients taking tocilizumab compared with etanercept.3
“This is reassuring for patients and clinicians,” Dr. Weinblatt said.
JAK Inhibitors
Jakinibs are a relatively new class of anti-rheumatic drugs that started being used clinically about eight years ago. Three Jakinibs are currently approved for use in the U.S.—tofacitinib, baricitinib and upadacitinib—with several more in development. Some of the perks are that Jakinibs are oral drugs, and “they work very fast, within a week,” said Dr. Weinblatt. “If you’re not better in eight weeks, they won’t work.”
The most recently approved Jakinib, upadacitinib, beat adalimumab in patients on background methotrexate in one randomized, blinded study, Dr. Weinblatt said.4 “This is the first time we’ve seen that: A JAK inhibitor plus methotrexate at the labeled dose in the [U.S.] beat adalimumab plus methotrexate statistically,” he added.
As with biologic therapies, Jakinibs have a known risk of infection—in particular, herpes zoster, which is hoped to be mitigated by the new shingles vaccine, although this needs to be studied, Dr. Weinblatt said. Other potential side effects include neutropenia, anemia, increased serum creatinine, liver function abnormalities, malignancy and, possibly, deep vein thrombosis (DVT) and pulmonary embolism (PE).
“The area of most concern now is this issue about leg clots and lung clots,” which first came to light in an April 2018 U.S. Food & Drug Administration (FDA) review of baricitinib, Dr. Weinblatt said. Information from Pfizer and the European Medicines Agency suggests older patients are particularly vulnerable.5-7
“What we know is that DVT and PE may be associated with use of selective JAK inhibitors—not all of them—but we don’t know what the mechanism behind it is,” Dr. Weinblatt said.
