Support for Biologics for Ankylosing, Axial Spondyloarthritis

ACR guidelines include TNF and IL inhibitors as second-line therapies.

The American College of Rheumatology, in partnership with the Spondylitis Association of America and the Spondyloarthritis Research and Treatment Network, has released updated guidelines that included 86 recommendations on patient management.

A major change lies in the recognition of the primacy of biologics for patients who don’t respond long term to first-line nonsteroidal anti-inflammatories. Biologics for rheumatoid arthritis, among related conditions, presents a new opportunity for patients and physicians. Howard Fuchs, M.D., director of the rheumatology training program at Vanderbilt University Medical Center, says the change acknowledges several important new drugs and formalizes a growing practice of offering them without the middle step of trying methotrexate, a drug that has shown limited effectiveness in this population.

“We are seeing excellent outcomes with biologics, particularly the newer ones that inhibit IL-17. Hopefully, these guidelines will help make them more available and eliminate having to try different drugs before insurance will cover them,” Fuchs said.

Moving to Biologics

Methotrexate is the drug of choice for rheumatoid arthritis, and historically also for psoriatic arthritis. It had also been the previously recommended second-line for ankylosing spondylitis and axial spondyloarthritis. “Methotrexate sometimes works for peripheral arthritis, but it tends not to effectively treat the arthritis of the spine or major joints,” Fuchs said. “With insurance requirements, we have sometimes had to go through hoops or try multiple INF inhibitors before moving to what we think will ultimately work best, which might be an IL-17 inhibitor.”

Alongside the battery of INF inhibitors (infliximab, etanercept, adalimumab, golimumab, certolizumab) that came out in the 1990s are several new IL-17A inhibitors, secukinumab, ixekizumab, and the JAK inhibitor tofacitinib. Tofacitinib is not a monoclonal antibody, but a small molecule that downregulates the intracellular machinery that creates inflammation in a totally different fashion.

“We are seeing excellent outcomes with biologics, particularly the newer ones that inhibit IL-17. Hopefully, these guidelines will help make them more available and eliminate having to try different drugs before insurance will cover them.”

The Cost of Biologics for Rheumatoid Arthritis

Biologics for rheumatic arthritis disorders can cost upwards of $25,000 annually. While similar drugs can be somewhat less expensive, the new guidelines recommend against making a switch if the biologic is working. Fuchs says that providers must be clear with patients about the balance of risks, benefits and costs.

It is challenging to help patients navigate uncertainties like variable insurance coverage, rigidly proscribed insurance mandates, and the timing and eligibility for free or reduced drugs from manufacturers, Fuchs said.

Elevated infection risk is a major consideration when taking immunosuppressing medications.

However, Fuchs says that this risk is not as high as many think. Most studies suggest about a doubling of the risk for incidence of conventional infections. Care must be taken to assure there is no active infection at the time of initiation of medications. Screening for tuberculosis and hepatitis B and C is required. It is recommended that use of these medications be avoided until any infections are effectively controlled.

The other risk that can deter patients from taking these drugs is the risk of malignancy, particularly lymphoma and nonmelanoma skin cancer.

Support for Physicians

Fuchs says that while doctors are enthusiastic about these medications, finding the right drug for each patient remains a challenge, and is a bit of an art.

“There are subtle differences between different types of inflammation, and different drugs work better accordingly,” he said. “I think these new guidelines offer physicians more support in using a nuanced approach appropriate to the indications we see.”