Questions Remain about Shingrix Safety in Rheumatic Disease Save

The efficacy and safety of the new zoster vaccine Shingrix has not been established among patients with autoimmune diseases, researchers reported here.

Clinical trials of the vaccine in adults ages ≥50 in the ZOE-50 trial, and ages ≥70 in the ZOE-70 trial showed very strong efficacy -- about 97%, compared with 40% to 50% for the older Zostavax vaccine. In the ZOE-50 study, 15,000 adults were randomized to the vaccine or placebo and followed for slightly over 3 years. During that time, there were six cases of shingles in the active treatment group compared with 210 cases in the placebo group.

In ZOE-70, which included 14,000 participants, there were 23 cases of shingles in this high-risk age group who received the active vaccine compared with 223 who were given placebo. Both studies were published in the New England Journal of Medicine and the vaccine was approved for use in the United States in October 2017.

"This is a really, really good vaccine," said Elizabeth Kirchner, MSN, CNP, from the Cleveland Clinic at the Ohio Association of Rheumatology (OAR) annual meeting.

"But the problem is that patients with immune-mediated inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and lupus were all excluded from those trials," she said.

Of particular concern is the adjuvant that was used in Shingrix, which has not been used before in humans.

"Adjuvants help the vaccine work. It's been known even since the smallpox vaccine was used that if you added an irritant, a little lye or soap, it worked better. For about 100 years the only adjuvant we had was alum, but now we have several more," Kirchner said.

The adjuvant used in Shingrix is an extract of the Quillaja saponaria tree native to Chile, which is a totally novel adjuvant that is unlike any previously used in vaccines, said Kevin Winthrop, MD, of the Oregon Health and Science University in Portland. "The efficacy of this vaccine is off the charts. No one has ever seen efficacy like this, and it's probably because of the adjuvant," he said at OAR.

The adjuvant is associated with significant reactogenicity, however, with up to 15% to 16% of patients having grade 3 systemic adverse events such as fever, myalgias, and flu-like symptoms that typically last for 2 days. "The worry is that this is going to cause flares in patients with lupus," he said.

"We know that adjuvants kick up the immune system, get the innate immune system going. But I'm not so excited about kicking up the immune system in a patient with lupus and not knowing what it's going to do to that patient's disease," Kirchner said.

This vaccine has been studied in HIV patients, cancer patients, and transplantation patients, and the patients did fine, she said. "But our concern is kicking up the immune system in autoimmune patients who already have a overactive immune system," she said.

Shingrix was given preference over the previous vaccine Zostavax by the FDA, but the vote among the Advisory Committee on Immunization Practices was only 8 to 7 in favor, Winthrop said. "This was hotly debated. One reason was a lot of people had concerns about the adjuvant. They were worried that if you give a preferential recommendation, physicians will start using it in subpopulations [such as autoimmune patients]," he said.

"There also have been concerns about creating autoimmune diseases over the long term. In the ZOE trials, patients were only followed for a few years," he said.

Careful postmarketing surveillance will be needed to ensure safety, he concluded.

Winthrop disclosed relevant relationships with AbbVie, Bristol-Myers Squibb, Galapagos, Lilly, Pfizer, and UCB.