The U.S. Food and Drug Administration’s Arthritis Advisory Committee voted 11 to 1 in 2011 against approving a biologic drug called Ilaris, or canakinumab, to treat gout. It cited safety concerns – adverse events, including increased rates of infection – despite a strong consensus that it is effective for treating gout attacks.

The positive results and an unmet need among a subset of patients may mean the drug’s potential as a gout treatment is not over. "I hope the company continues to work with the FDA to address the concerns raised, given the promising efficacy of the drug," says Tuhina Neogi, MD, PhD, a consultant to the Arthritis Advisory Committee and an associate professor of medicine at Boston University Medical Center.

Ilaris was approved two years earlier  to treat a group of rare inflammatory conditions called cryopyrin-associated periodic syndromes, or CAPS. Drug maker Novartis later submitted a supplemental application to the FDA for treatment of gouty arthritis.

Gout is a type of inflammatory arthritis that affects nearly 6 million Americans, according to the Centers for Disease Control and Prevention. It occurs when high levels of uric acid in the blood form uric acid crystals that settle into joints and the soft tissues surrounding them. The accumulation of crystals in the joint does not cause symptoms, so people are rarely aware of their condition until the first attack: a sudden and rapid escalation of inflammation – at first, typically in a single joint and often, but not always, in the big toe – causing extreme pain.

Gout, sometimes referred to as gouty arthritis, occurs in some people who have a metabolic disorder causing chronic overproduction or under-elimination of uric acid. Long-term management focuses on medication and lifestyle changes to lower uric acid levels, potentially eliminating or reducing the crystal deposits and subsequent attacks.

The gout attack, however, is driven by inflammation. Each attack resolves within a couple of weeks, even without treatment. But the inflammation and immediate pain is so excruciating and debilitating that medication is used to relieve the attack more quickly and often is continued to minimize risk of further attacks while uric acid lowering medication is initiated and levels stabilized.

During an acute gout attack, doctors use a nonsteroidal anti-inflammatory drug, or NSAID, such as indomethacin or naproxen. Colchicine and corticosteroids, including prednisone and triamcinolone, are other common options to provide relief, especially in patients who cannot tolerate NSAIDs.

Ilaris, administered as an injection, works by targeting the inflammatory cytokine interleukin-1beta, or IL-1. The proposed indication was for treating gouty arthritis attacks in people who do not respond to NSAIDs or colchicine, as well as extending the time to the next attack and reducing the frequency of attacks.

John Sundy, MD, a rheumatologist at Duke University Medical Center in Durham, N.C. – and a medical consultant for Novartis – says the standard approach to treating gout attacks won’t likely change even if Ilaris is eventually approved.

“If what people are using is working for them just fine, [they] don’t [need to] switch. But it [would be] great to have this option,” Dr. Sundy explains. “I think most people will remain with NSAIDs to treat their gout attacks. One, they are very effective, and two, they are very inexpensive.”

The Arthritis Advisory Committee reviewed two studies of more than 450 gout patients taking 150 milligrams of Ilaris over six months. The drug was found to be effective at reducing both the pain and the recurrence of gout flares, but it also came with a greater risk of serious infections than the comparison drug, the corticosteroid triamcinolone, and with a potential for kidney damage.

"Many members of the FDA panel recognized and said that there is still an unmet need in the treatment of acute gouty arthritis, but I think it was clear committee members had concerns with the proposed indications for use of this agent in the current application," explains Lawrence Edwards, MD, a professor of medicine in the division of rheumatology at the University of Florida School of Medicine in Gainesville and a member of the Novartis presentation group at Tuesday's meeting.

In a written statement posted on the company’s website, the global head of development at Novartis Pharmaceuticals, Trevor Mundel, MD, said, “We continue to believe in the benefits of [Ilaris] for this painful and debilitating disease and will work closely with the FDA to identify the right patient population who will benefit from this therapy."