Role of Anti-TNF Therapy in Spondyloarthritis

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Philip J. Mease, MD, and John D. Reveille, MD, highlight the role of TNF inhibitors in psoriatic arthritis and ankylosing spondylitis.

Philip J. Mease, MD: Typically, the first-line of disease-modifying therapy that we use in psoriatic arthritis is either methotrexate, sulfasalazine, or leflunomide. Although there’s not a lot of evidence for their efficacy, we certainly have some clinical experience that these medicines can be at least partially helpful for treating psoriatic arthritis. So, they’re typically the starting place.

However, the majority of patients do not respond adequately to these medications, or they may have side effects. And so really the gold standard that we’ve been using over the last 15 years has been the anti-TNF medications.

There are five anti-TNF medications that are approved for the treatment of psoriatic arthritis. These are etanercept, adalimumab, infliximab, golimumab, and certolizumab.

The efficacy of these drugs is very similar when it comes to the musculoskeletal domains. When it comes to the skin disease, however, the monoclonal antibody constructs are slightly superior to the agent etanercept, which in its standard does not work as well in the skin.

All of these medications have good effects on other clinical domains besides arthritis and skin disease, and that includes enthesitis, dactylitis, and the other features such as function improvement, quality of life improvement, and fatigue improvement. And very importantly, all of the anti-TNFs have been shown to inhibit progressive structural damage as measured by radiographs of joints. So, the anti-TNFs have really historically been the gold standard for treating psoriatic arthritis, and we are able to get many patients into remission or low disease activity with these drugs.

There are limitations though in their use. For example, we often find that patients will eventually lose response to a medication. There may be different reasons for this, including the potential for developing antibodies against the drug—which may diminish response. Or there may be other biological reasons that their effect is diminished.

We also find that some people run into safety or tolerability problems with the anti-TNF medications. And for this reason, we have historically either switched between anti-TNF medicines or—now that newer drugs are being approved with a different mechanism of action—we’re switching patients to the newer medications in order to try to maintain whatever efficacy has been achieved with the anti-TNF medications historically.

John D. Reveille, MD: Anti-TNF therapy, of course, has to be given with caution. You do not want to be giving anti-TNF therapy to someone with a chronic hepatitis B infection, as they have a 70% chance of a major flare of their chronic hepatitis. You want to screen for HIV or hepatitis C just to be aware that there are guidelines. Generally, clinical trials exclude such patients. We’ve actually shown in our publications from our work that you can use anti-TNF agents in the setting of either hepatitis C or HIV, provided the patient is not significantly immunosuppressed. We do use that.

We then will want to warn the patient about, and screen the patient for, tuberculosis (TB) because there’s a bug called mycobacteria—which is an issue as far as TB is concerned in patients taking anti-TNFs. It’s probably the main infection we worry about, but other mycobacterial infections also had to be taken into caution. There are other types of mycobacteria like mycobacterium avium-intracellulare—which we sometimes see in our patients getting anti-TNF agents—or, what we see in East Texas and Louisiana, mycobacterium leprae—which classically known as leprosy. So, someone who’s been working with armadillos probably needs to be very careful with anti-TNF agents. We have seen it. If they live in other parts of the country where there are chronic fungal infections that are present, whether it be in Arizona or the San Joaquin Valley where you worry about certain fungi very common up there. You want to make sure that you screen with blood tests, that that is not present in the patient, or if they have a recent infection with it. It’s called coccidioidomycosis.

Certain other areas, such as Tennessee, Kentucky, etc., in the Appalachians you worry about histoplasmosis. That’s also something that can be triggered or worsened by anti-TNF agents. But, other than that, these patients tend to tolerate that well. There is a very low risk of lymphoma associated with this, and some emerging data that suggests that there might be also a high risk of non-melanoma skin cancers like basal cell carcinoma. Patients should use sunscreen and not try to bake in the sun too long.