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PsA is a chronic inflammatory condition that affects the joints and skin. It is an autoimmune disease that occurs when the immune system mistakenly attacks the body’s tissues. This leads to tissue damage, pain, and inflammation. PsA has no cure, but treatments are available to help slow the progression of disease, reduce pain, and minimize joint damage. To treat the underlying inflammation that causes arthritis, doctors prescribe disease-modifying antirheumatic drugs (DMARDs). Doctors use many types of DMARDs to treat PsA. Some DMARDs work by broadly suppressing the immune system — these are commonly called conventional or synthetic DMARDs. Targeted DMARDs that specifically inhibit immune factors involved in PsA are also available. Doctors generally use these as preferred agents to treat persistent or severe disease. For many years, biologic DMARDs, also called biologics, were the only targeted DMARDs available to treat PsA. However, the Food and Drug Administration (FDA) has recently approved a new class of medications, known as JAK inhibitors, for targeted treatment of PsA. In this article, we will review the similarities and differences between how biologics and JAK inhibitors work and how doctors use them in the treatment of PsA. What are biologics Biologics are a type of medications that are derived from biological sources rather than artificially made. They provide more targeted suppression of disease-causing pathways than conventional DMARDs. This may help improve their effectiveness or reduce off-target effects over nonspecific treatments. To treat PsA, doctors use five types of biologics, which target different components of the immune system:TNF-alpha inhibitors: Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), and Simponi (golimumab)IL-12/IL-23 inhibitor: Stelara (ustekinumab)IL-23 inhibitors: Skyrizi (risankizumab-rzaa) and Tremfya (guselkumab)IL-17 inhibitors: Cosentyx (secukinumab), Siliq (brodalumab), and Taltz (ixekizumab)T cell inhibitor: Orencia (abatacept) By blocking the activity of these factors, biologics work to reduce inflammation and prevent joint damage. A person receives biologics via injection or infusion. Doctors may use biologics alone or in combination with conventional DMARDs such as methotrexate. There are also biosimilar medications, which are modeled after a reference biologic and offer a similar treatment result. Pharmacists may substitute these for biologics. Biosimilar medications may come at a lower cost than biologics. The biosimilars approved to treat psoriatic arthritis are: Amjevita (adalimumab-atto), Abrilada (adalimumab-afzb), Cyltezo (adalimumab-adbm), Hadlima (adalimumab-bwwd), Hulio (adalimumab-fkjp), and Hyrimoz (adalimumab-adaz), which are biosimilar to Humira (adalimumab)Erelzi (etanercept-szzs) and Eticovo (etanercept-ykro), which are biosimilar to Enbrel (etanercept)Avsola (infliximab-axxq), Inflectra (infliximab-dyyb), Ixifi (infliximab-qbtx), and Renflexis (infliximab-abda), which are biosimilar to Remicade (infliximab) What are JAK inhibitors JAK inhibitors are small molecules that block signals transmitted by the Janus kinase (JAK)-signal transducer and activator of transcription (STAT), or JAK-STAT, pathway. Many components of the immune system use this signaling pathway, and it is a known regulator of inflammation in a variety of diseases. Like biologics, JAK inhibitors target specific molecules related to inflammation in PsA. However, unlike biologics, these medications are synthetic, which means they are less expensive to manufacture. It also means that people can take them orally rather than receive them as injections. The two JAK inhibitors approved to treat PsA are Xeljanz (tofacitinib) and Rinvoq (upadacitinib). JAK inhibitors are the newest type of medications approved to treat PsA. The FDA approved the first one, tofacitinib, for PsA treatment in 2017. Biologics vs JAK inhibitors for PsA Although research has shown that both types of medications can be effective treatments for PsA, clinical trials comparing biologics and JAK inhibitors head-to-head are limited. The SELECT-PsA 1 clinical trial directly compared a JAK inhibitor (upadacitinib) with a biologic (adalimumab) in more than 1,700 people with active PsA. In this study, participants who received 15 mg of upadacitinib once daily had reductions in joint swelling, tenderness, and pain that were similar to the effects observed in participants who received 40 mg of adalimumab every other week. However, participants who received a 30-mg dose of upadacitinib had greater improvements in disease measures than those who received adalimumab. This suggests that a higher dose of upadacitinib may provide better disease regulation and symptom relief. Although research has not yet directly compared tofacitinib with biologics, evidence from the OPAL Broaden trial suggests that tofacitinib (5 or 10 mg twice daily) provides similar levels of relief as adalimumab relative to a placebo control in regard to both disease measures (swelling, pain, and tenderness) and patient-reported outcomes, such as fatigue, ability to function, and quality of life. Research also suggests that tofacitinib can help reduce symptoms of PsA in approximately half of people who do not respond well to TNF inhibitor biologics. Role in PsA treatment PsA is a heterogeneous disease — no two people experience it the same way, and everyone responds differently to treatment. Guidelines and recommendations are available from several large professional organizations that serve people with PsA, but ultimately treatment will depend on how a person responds to the various medications. In general, experts recommend using biologics ahead of JAK inhibitors for PsA treatment. Typically, this involves the use of a TNF inhibitor first. According to most recommendations, JAK inhibitors such as tofacitinib are reserved for people who cannot take a biologic or do not respond well to biologic therapy. However, some experts have suggested using JAK inhibitors earlier in PsA treatment. This is because recent results demonstrate that JAK inhibitors produce effects more quickly than biologic therapy and because taking a pill is more convenient than receiving a shot or infusion. More research is necessary to determine how these treatments compare in terms of effectiveness. Until more research is available, doctors will likely make decisions on the use of biologics and JAK inhibitors in PsA treatment on a case-by-case basis, depending on disease features and personal considerations. Safety considerations In addition to effectiveness, safety is an important consideration when choosing treatment for PsA. Any medication comes with a risk of side effects, and it is important to weigh the potential risks and benefits when deciding on an approach to treatment. In 2021, the FDA added warning labels to certain JAK inhibitors, including those that doctors use to treat PsA. Long-term use of these medications can increase the likelihood of developing serious complications, including:heart-related eventscertain types of cancerblood clots In some cases, these complications could be fatal. For this reason, doctors generally do not recommend JAK inhibitors for people who: smoke or have smokedare at risk for heart diseasehave certain types of cancer The FDA limits the use of JAK inhibitors to people who have not responded well to other types of PsA medications, including biologics. Because they work to suppress the immune system, both biologics and JAK inhibitors may also increase the likelihood of infections. People taking these medications should contact their healthcare team right away if they develop any symptoms of illness, such as a fever or cough. The takeaway The treatment landscape for PsA is growing, and many new targeted treatment options are available. Biologics and JAK inhibitors offer an opportunity to suppress the specific causes of inflammation involved in PsA, minimizing the need for broad immunosuppressants in PsA treatment. Both types of medications may effectively reduce symptoms in people with PsA. Their use in PsA treatment is evolving, but biologics — especially TNF inhibitors — are currently the preferred therapy given their safety and effectiveness. However, everyone with PsA responds differently to treatment. A rheumatologist will work closely with the people in their care to help determine the right treatment approach for each person. 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