From healthcentral.com
Medications for psoriatic arthritis are rarely one and done. Here’s guidance on how to know it’s time for a change
The right treatment plan is crucial to control symptoms of psoriatic arthritis (PsA), a chronic, inflammatory condition characterized by joint pain, stiffness, and swelling. But many people living with PsA don’t respond to first-line treatments prescribed by their rheumatologist at the time of diagnosis. “There is no single therapy that is best for everyone with psoriatic arthritis,” says Veronika Sharp, M.D., an affiliated clinical professor at Stanford University School of Medicine and chief of the division of rheumatology at Santa Clara Valley Healthcare in San Jose, CA. “Patients may have to try multiple medications to find the type that works best for them.”
Like many other autoimmune diseases, psoriatic arthritis comes with potentially debilitating and life-changing consequences due to the pain and challenges with physical activity. And although we have many more treatment options now than we did 20 years ago, none of them are curative.
Current guidelines from the American College of Rheumatology and the National Psoriasis Foundation advise the use of tumour necrosis factor (TNF) inhibitor biologics, such as infliximab or adalimumab, as the first-line treatment for PsA. They suggest that people whose symptoms don’t improve with their first TNF inhibitor should try another TNF inhibitor.
But there is no one-size-fits-all approach for treating psoriatic arthritis. And if your first PsA treatment didn’t work, there are many reasons to stay hopeful. “There has been tremendous progress in treatment of psoriatic arthritis in the past few years,” says Dr. Sharp. “While doctors continue to use traditional disease modifying drugs (DMARDs) and TNF inhibitor biologics, which have been around for years, there are now a number of other therapies with different mechanisms of action, including several other classes of injectable biologics and new oral medications.”
Let’s dig into the second-round PsA treatments worth learning about.
Injectable Biologics
While there have been several new treatments for psoriatic arthritis approved by the Food and Drug Administration (FDA) within the last five years, Michelle T. T. Ngo, D.O., a rheumatologist with Providence St. Jude Heritage Medical Group in Fullerton, CA, highlights the IL-17 inhibitor and IL-23 inhibitor therapies—both injectable biologics—as “game changers.”
There are three IL-17 inhibitors approved by the FDA to treat psoriatic arthritis: secukinumab, ixekizumab, and brodalumab. They all work in the same way—by targeting the IL-17A receptor, they block its inflammatory pathway to help reduce inflammation and improve psoriatic arthritis symptoms.
As for IL-23 inhibitors, risankizumab was approved for the treatment of active PsA in adults in 2022. A phase 2 study of the biologic tildrakizumab, which also targets IL-23 and stops the release of inflammatory, showed a significant improvement of most joint- and skin-related symptoms (with few side effects), and phase 3 studies are currently ongoing.
“These more targeted therapies essentially allow rheumatologists to get a handle on inflammation without blocking as much of the immune system that is important for cancer and infection detection,” Dr. Ngo explains.
Oral Medications
The newest class of drugs approved by the FDA to treat psoriatic arthritis is called Janus kinase (JAK) inhibitors. These are taken daily in pill form and work in a more targeted way than traditional disease-modifying psoriatic arthritis treatment options, by blocking immune response pathways believed to be specific to PsA. This reduces the inflammation that fuels psoriatic arthritis (and other inflammatory diseases).
Most recently, upadacitinib was FDA-approved for the treatment of active psoriatic arthritis in adults who have had an inadequate response or intolerance to one or more TNF blockers. The results of phase 3 trials were promising, with participants reporting improvements in joint pain and physical function.
Deucravacitinib, a new tyrosine kinase 2 inhibitor, works in a similar way to JAK inhibitors and appears to be as safe. Participants in a phase 2 study experienced symptom improvement, and phase 3 studies are currently ongoing.
Doubling Up on Biologics
Several case studies as well as promising findings from phase 2 clinical trials suggest that combining two biologics could be an alternative strategy to improve patient response to treatment.
Researchers working on the VEGA trial found that combining the IL-23 inhibitor guselkumab and the anti-TNF agent golimumab was more effective than either drug used alone as an initial treatment for moderate to severe ulcerative colitis—another autoimmune-driven condition—with almost no adverse side effects. The AFFINITY trial is now trying the same combination therapy for patients with active PsA.
Reports have also highlighted the possible benefits of combining a TNF inhibitor and an IL-17 inhibitor in the treatment of rheumatoid arthritis (RA) and PsA, as well as the combination of a TNF inhibitor and an IL-23 antagonist for PsA. However, these combinations require controlled clinical trials.
How to Know When It’s Time to Discuss a Change
Generally, doctors still follow a stepwise approach to treat PsA. “We recommend starting off with the less immunosuppressive therapies and working our way up systematically to protect our patients from the secondary side effects of autoimmune treatment, namely their increased risk for infections,” says Dr. Ngo. “Our focus in rheumatology is treating to target disease stability.”
If you’re trying a new med and not seeing results, be patient. “Often, it takes three to six months to see meaningful clinical change when we start a PsA patient on a new therapy, so it’s not uncommon to see flare ups during this time,” Dr. Ngo says. That’s because the origin and development involve many different mechanisms (including combinations of genetic and environmental factors), and scientists haven’t yet been able to pinpoint all the different genes involved in disease activity. As a result, it’s common for PsA patients to try multiple treatments before discovering the right pathway, says Dr. Ngo.
All medications come with possible side effects—in the psoriatic arthritis field these range from diarrhoea and nausea with oral meds to an increased risk of infections with biologics, per the Mayo Clinic. “Side effects are something we take seriously in rheumatology because of the multisystem effects of our medications,” says Dr. Ngo. “Routinely, we will counsel the common side effects that may come with treatment. Often, medications will have a ‘warming up’ period which may come with mild symptoms that gradually wane over the course of treatment, hopefully within two to four weeks.”
After four weeks, if any side effects are intolerable—to the point where they affect a patient's daily activities—Dr. Ngo says it would be reasonable to consider discussing other treatment options. “This is of course as long as there are no existing drug interactions or other underlying medical conditions which may prevent the rheumatologist from switching to another drug easily,” she adds. “We will treat to target and tailor the drugs to fit our patients' needs and we do so by having lengthy discussions and shared medical decision making.”
Side effects aside, if you’re not seeing an improvement in your symptoms after six to 12 months, Dr. Ngo believes it’s reasonable to take a step back and re-assess if other conditions may contribute to your symptoms.
Generally, if you’re having flare ups of your PsA symptoms that are longer, more frequent, or more severe than usual, it may be time to reassess your treatment plan. Working with your doctor will help you gain the best possible control over your condition.
https://www.healthcentral.com/condition/psoriatic-arthritis/your-psa-treatment-failed-now-what
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