Factors to Consider in Treating Spondyloarthritis

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John D. Reveille, MD, and Philip J. Mease, MD, discuss the safety and efficacy of considering a new treatment for spondyloarthritis, specifically the use of IL-17 inhibition and methotrexate.

Philip J. Mease, MD: Because of the heterogeneity of manifestations of psoriatic arthritis—the multiple clinical demands that can occur—we’re looking for medications which can affect all of the domains that affect the patient. Fortunately, the new medications that have been approved all have shown benefit in these areas. The one exception is that we don’t have radiographic data with apremilast. So, if a patient has demonstrated evidence of significant structural damage progression, then we might prefer to use a biologic medication. But other than that, I think that all of the new medications are efficacious and have shown relatively good safety profiles. The good news is that we can use all of them with a relatively high degree of confidence.

John D. Reveille, MD: As we consider what patients should be best prescribed these biologic treatments, we want to first make sure that we’re dealing with a patient with active disease. In a patient that doesn’t have contraindications to the use of it, such as having chronic hepatitis B, you want to make sure that the patient is able to afford the drug—cost is a big issue obviously, especially in these politically charged times in which we live—and that they don’t have any other contraindications, such as a lymphoma or other cancers, that may complicate the use of these drugs.

When do you consider using one of these newer drugs? The answer is that if a patient has been on at least two nonsteroidal anti-inflammatory agents over a 3 month period and failed to have significant clinical response, they can be considered at that point. In the community setting, there’s no reason why they can’t be used. They’re effective. Their safety profile is not bad. Probably the major concern would be in a patient who had evidence of recent active inflammatory bowel disease, that a flare can be triggered by the use of these agents—which contrasts the anti-TNF agents where you would not expect that. But, otherwise, if the patient has not responded to nonsteroidal anti-inflammatory drugs and has persistent axial pain, axial spondyloarthritis, or ankylosing spondylitis, there’s no reason not to consider these drugs.

Philip J. Mease, MD: Based on the efficacy and safety profile of secukinumab, from my perspective, there’s no reason why we couldn’t use it as a first-line agent for treating psoriatic arthritis. Realistically, many of the patients that will initially be treated with it will have been tried on a variety of other medications previously, ranging from methotrexate to anti-TNF therapy, to even possibly some of the newer medications. But eventually we’re going to be using it more first-line, and I think that that’s going to be a potentially very good place for it.

Having said that, we know from the clinical trials that even in patients who have tried several anti-TNF agents previously, the drug is effective. And so even later on in the treatment ladder, I think it’s going to be very useful. So, really, we can slot secukinumab anywhere into the treatment ladder and especially for patients with severely active disease, both in the skin and musculoskeletal elements.

An important question is where methotrexate should be used concomitantly with either the approved biologics for psoriatic arthritis or the new oral medication apremilast. The paradigm that has been established in the care of rheumatoid arthritis patients is that, ideally, methotrexate is used along with biologics to increase the clinical response and increase the ability to inhibit radiographic progression, as has been demonstrated in a number of studies with anti-TNF medications.

It is not as clear that that paradigm holds true for psoriatic arthritis. We also know that methotrexate may have special risk in a psoriatic arthritis population. Because of the proclivity to metabolic syndrome, including obesity, there’s an increased chance for having fatty liver in a patient with psoriatic arthritis. This means that if you’re taking a medication that may be hepatotoxic, such as methotrexate, there may be an increased chance for liver injury—as demonstrated, for example, by increased liver enzymes and historically by liver biopsy studies.

Also, dermatologists who have treated the patients previously for their psoriasis may have inculcated in their patients a certain concern about use of methotrexate. So, these are the issues that we face when discussing the use of this medication with our patients.

Now, clearly there are some circumstances when methotrexate background may be important. For example, if we’re working with the use of an anti-TNF medicine that has a higher chance for immunogenicity, such as a chimeric antibody, then it may be more important to use concomitant methotrexate to reduce the chance for development of antibodies against the biologic medication. And there’s some evidence that even with some of the biologics that don’t have as much of a problem with antibody formation, still, background methotrexate may reduce a chance for antibody development and possibly may improve efficacy. So, in some circumstances, we do find that bridging by continuing methotrexate, and along with the biologic, may be very useful.

But there’s also evidence in clinical trials that you don’t have to do this. And so many patients—who either don’t like the side effects of methotrexate or don’t like the restriction against alcohol use or other factors—may appreciate knowing that they can use their medication, be it an anti-TNF or one of the newer medicines—such as ustekinumab or apremilast or secukinumab—as a monotherapy. There’s good evidence that they can work in that way.

So, it’s not a completely settled question whether there is importance in using a methotrexate background. In some instances, it may help with reduction of immunogenicity when you’re using biologics. But, also, we’re confident that with all of these medications, they can be used as monotherapy and the patient will still benefit.