AxSpa treatment expands beyond 'workhorse' TNF inhibitors
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Strong data for two interleukin-17 inhibitors have given a lift to clinicians treating the spondyloarthropathies, according to a presenter at the 2020 Congress of Clinical Rheumatology-West.
“After quite a while, we have finally got medications besides TNF inhibitors, which have been our workhorses for quite some time,” Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, said in his presentation.
While TNF inhibition remains the recommended first-line biologic approach in patients with non-radiographic or radiographic axial spondyloarthritis, IL-17 inhibition is recommended over a second TNF inhibitor as a second-line approach, according to the 2019 American College of Rheumatology (ACR)/Spondylitis Association of America (SAA)/Spondyloarthritis Research and Treatment Network (SPARTAN) recommendations.
Secukinumab (Cosentyx, Novartis) and ixekizumab (Taltz, Lilly) are the two IL-17 inhibitors named in this portion of the document. These two drugs, along with a second TNF inhibitor, are all recommended as second-line treatment over tofacitinib (Xeljanz, Pfizer), according to Mease.
That said, switching to a second TNF is not out of the realm of possibility, according to Mease. “Registry studies looking at whether it makes sense to switch from a first TNF to a second TNF have found that the answer was yes,” he said. “So, it is legit to try.”
Mease dug into some particulars surrounding secukinumab and ixekizumab. His first point was that secukinumab is not only a strong second-line option, but also that emerging data are showing that it can be effective in the first line.
That said, he did note an “uptick” in candida infections among patients treated with secukinumab. “We know IL-17 protects against surface candida,” he said.
An additional concern pertains to Crohn’s or ulcerative colitis. “There is some increase of frequency of flare or previously known Crohn’s or ulcerative colitis [with secukinumab], or a smaller handful of cases of new onset Crohn’s or UC,” he said.
As for uveitis incidence with secukinumab, it remains “uncertain,” according to Mease.
Regarding ixekizumab, Mease noted data showing that the drug may be effective in TNF-naïve or TNF-experienced patients.
Looking deeper into the armamentarium, Mease noted that while etanercept (Enbrel, Amgen) is not currently approved in non-radiographic axial spondyloarthritis, the drug has shown signs of efficacy. The same could be said for golimumab (Simponi, Janssen), which Mease reported has “clear cut efficacy” in non-radiographic disease.
On the horizon is the IL-17 inhibitor bimekizumab (UCB), which Mease suggested is showing promise at various dosing levels.
Turning to other mechanisms of action, while janus kinase (JAK) inhibition with tofacitinib is not recommended as second-line therapy, the drug has performed “really well” in recent studies and is moving to phase 3, according to Mease.
Upadacitinib (Rinvoq, Abbvie) is also proceeding through clinical trials, Mease added. “I am hopeful that at some juncture we will have a good oral treatment option for ankylosing spondylitis.”
One approach that has gained attention pertains to withdrawing adalimumab (Humira, Abbvie) in patients in disease remission. “What we saw was that there was a clear falling off in efficacy in patients who had adalimumab withdrawn,” Mease said.
He suggested this result, in itself, was “not too surprising,” but that there was a further data point to consider. Among patients in the withdrawal arm of the study, 41% who went back on the drug failed to re-achieve remission. “This is a bit of a warning about stopping drug.”
Mease also addressed the controversy surrounding background methotrexate, sulfasalazine or leflunomide in patients being treated with biologics.
Some data show higher drug retention with background methotrexate or sulfasalazine, but other data showed that comedication with conventional synthetic DMARDs had no impact on drug retention, which Mease noted is often used as a “surrogate for efficacy.”
“My conclusion is that the matter is still not completely settled,” Mease said. “It is not irrational to consider use of background methotrexate, especially to produce drug retention.”
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Mease PJ. Treatment of Axial Spondyloarthritis, 2020. Presented at: Congress of Clinical Rheumatology-West annual symposium; October 8-11, 2020 (virtual meeting).
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