Biologics for psoriatic arthritis

Biologics and PsA: What Are Your Options?

There are several options to treat your PsA with a biologic. These drugs can be grouped together by your doctor based on how they act in relation to the immune system.

TNF-alpha inhibitors

Tumor necrosis factor-alpha (TNF-alpha) is a protein that leads to inflammation. People with PsA have excessive amounts of TNF-alpha on their skin or in their joints.

These five drugs are designed to block this protein:

  • Cimzia (certolizumab pegol)
  • Enbrel (etanercept)
  • Humira (adalimumab)
  • Remicade (infliximab)
  • Simponi (golimumab)

They work by stopping the excessive growth of skin cells and inflammation that can lead to damage of joint tissue.

IL-12, IL-23, and IL-17 inhibitors

Interleukin-12, interleukin-17, and interleukin-23 are different proteins associated with inflammation. Five biologics currently available will interfere with the activity or with the corresponding receptor of these proteins.

These medications are designed to prevent inflammation:

In people who have arthritis, T-lymphocyte cells, or T-cells, are activated, which can lead to a proliferation of these cells. Some people with arthritis will actually develop an excess of T-cells.

These are immune cells, which we all need. But in large amounts, they produce chemicals that lead to joint damage, pain, and swelling.

Orencia (abatacept) is a medication that affects T-cells. Orencia doesn’t reduce the number of T-cells, but it does stop the emission of the chemical that causes symptoms by blocking T-cell activation.

JAK kinase inhibitor

Xeljanz (tofacitinib) is another medication approved for PsA. It’s a JAK kinase inhibitor, which refers to a small molecule that blocks a pathway involved in the immune system’s inflammation response.

This medication is not technically a biologic, but your doctor may talk to you about it. It’s often grouped together with biologics in discussions about more targeted agents for autoimmunity.

Biologics

Biologics are a recent addition to the clinician’s list of prescribable drugs for psoriatic arthritis.

They act by mimicing the effects of substances naturally made by the immune system of the patient. They are manufactured using genetic engineering, meaning that human genes that normally guide the production of these natural human immune proteins (i.e., an antibody to TNF) are used in artificial ways to produce large amounts of a biologic drug. These drugs are given to lessen inflammation by interfering with biologic substances that cause or worsen inflammation.

Biologic agents have been approved to treat moderate to severe psoriatic arthritis that has not responded to one or more of the traditional disease modifying antirheumatic drugs DMARDs. They are not generally considered as first-line treatments because of their expense and side effects, unless patients are unable to take methotrexate because of side effects or other conditions. Biologic agents may be used alone, but are often given in conjunction with other DMARDs to increase the benefit and limit potential side effects. When patients start biologic agents, they usually also remain on their current dose of non-steroidal anti-inflammatory NSAIDs and/or corticosteroids (i.e., prednisolone) medicines.

Currently available biologic agents act as inhibitors of the cytokines, IL-1 or TNF. Cytokines are messenger molecules made by many of the body’s cells that act to excite other immune system cells. Interleukin-1 (IL-1) and tumour necrosis factor (TNF) are made in large amounts in rheumatoid arthritis and other forms of inflammation. TNF or IL-1 acts to increase inflammation, similar to the effect of adding petrol to a fire. Hence, these molecules amplify and worsen inflammation and joint damage. Biologic agents specifically attach to TNF or IL-1 and inhibit or inactivate them.

Biologic agents are given by injection and usually work quickly to relieve the symptoms and swelling associated with psoriatic arthritis. Although the studies show that most patients will improve within 4-6 weeks of treatment, most patients will notice some improvement after the first or second injection.

The most common side effects seen with all injectable medicines include skin reactions at the injection site. These occur in less than 30% of patients. These skin reactions may last for between 1 and 2 weeks. The most significant side effect of these medications is an increase the risk of all types of infections, including tuberculosis (TB). Before starting an anti-TNF medication a TB skin test is usually done. Treatment with these agents should be stopped while you have an active infection and are taking an antibiotic or if you have a high fever. People with significant congestive heart failure should not take the anti-TNF agents.

Current available biologic agents

  • Infliximab
  • Etanercept
  • Adalimumab
  • Golimumab
  • Certolizumab pegol
  • Ustekinumab
  • Biosimilar

Although choosing a biologic therapy for psoriatic arthritis can be complex, recent guidelines and head-to-head trial data provide some indications of which agent to use first — and second, Kristina Callis Duffin, MD, said in a presentation at the 2019 annual meeting of the American Academy of Dermatology in Washington, D.C.

The most recent published guidelines call use of TNF inhibitors as first- and second-line therapy, but include “caveats” that would steer certain patients toward other biologics or even to oral therapies such as methotrexate, said Callis Duffin, co-chair of the department of dermatology at the University of Utah, Salt Lake City, and President of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

“Which biologic should we choose first?” is a common question asked by patients and physicians alike, Callis Duffin told attendees in a presentation that addressed treatment decision making in a time of “biologic overload” due to a plethora of approved systemic therapies.

Choosing a Biologic for Psoriatic Arthritis

Often, choosing a biologic for psoriatic arthritis comes down to the “two birds, one stone” approach, according to Callis Duffin. In other words, therapies are often chosen that will positively affect two conditions, such as psoriasis and psoriatic arthritis, or Crohn’s disease and psoriatic arthritis. However, choice may also be influenced by the degree of skin and joint severity, and should involve a consultation with a rheumatologist, she said.

That choice can be daunting and dizzying, with more than 14 approved systemic or biologic agents approved for psoriasis and/or psoriatic arthritis, including oral molecules such as methotrexate and tofacitinib, TNF inhibitors, IL-17 inhibitors, and IL-12/23 or IL-23 inhibitors. A few, tofacitinib and golimumab, are approved only for psoriatic arthritis, while the IL-17 inhibitor brodalumab is indicated for plaque psoriasis but not yet for psoriatic arthritis, though it has “good efficacy” in that setting, according to Callis Duffin. Among the IL-12/23 and IL-23 inhibitors, ustekinumab has data and an indication in psoriatic arthritis, she added.

What do the Guidelines Say?

Until recently, there have been few published recommendations to guide treatment choice in psoriatic arthritis. In 2015, GRAPPA issued treatment recommendations for psoriatic arthritis that are somewhat complex and hard to negotiate, in the speaker’s estimation.

The GRAPPA recommendations include a schema based on six principles of the disease, including arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities. “As GRAPPA president and a dermatologist, I’ll just be very honest — I find these guidelines from GRAPPA to be very different to interpret,” she said, noting that multiples of those domains might be observed in individual patients to different degrees, leading to many different permutations.

Newer treatment guidelines, which may be a little more conducive to nudging clinicians toward a decision, were recently released by the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF).

Those guidelines, which appeared in January in the Journal of Psoriasis and Psoriatic Arthritis, incorporated input from dermatologists, rheumatologists, patients, and other stakeholders to evaluate available therapies on ACR response criteria, safety, and quality of life scores, Callis Duffin noted.

TNFs in First and Second Line, With Caveats

For a treatment-naïve patient with psoriatic arthritis, guidelines say that TNF inhibitors should be considered as first-line therapy, and that they are recommended over IL-17 and IL-12/23 biologics, but with caveats. Specifically, the guidelines allow that oral systemic treatment (i.e., methotrexate) can be considered for patients who want oral treatment, and that different classes of biologics might be considered for patients with more severe psoriasis.

After TNF inhibitor failure, the recommended second-line treatment is again a TNF inhibitor, although again, there are caveats that other classes of agents can be considered for more severe disease or for patients with contraindications to TNF inhibitors, Callis Duffin added.

Head to Head Data Are Coming

There are few head-to-head studies of biologics for psoriatic arthritis, but some data are emerging from recent studies, and those data could have implications for the current TNF recommendation, according to Callis Duffin.

One of the studies is SPIRIT-H2H, a randomized, multicenter trial comparing the IL-17A inhibitor ixekizumab to adalimumab. This is the first large head-to-head (H2H) superiority study in active psoriatic arthritis to be completed, according to Lilly, which reported results in a recent press release. After 24 weeks of treatment, patients on ixekizumab were more likely to achieve ACR 50 and PASI 100 as compared to patients on adalimumab, according to the reported results.

“Stay tuned for more data on that study,” the speaker told attendees.

Exceptions to the Rule

The recent ACR/NPF guidelines include some exceptions to preferred TNF therapy. For patients with axial disease, reasonable choices include NSAIDs, physical therapy, TNF inhibitors, and IL-17 inhibitors. Following failure of an NSAID, a TNF inhibitor would be recommended over an IL-17 or IL-12/23 biologic, and an IL-17 biologic would be recommended over an IL-12/23 biologic, Callis Duffin noted, citing the guidelines.

Three randomized trials of the IL-12/23 biologic ustekinumab in axial spondyloarthritis patients were stopped after primary and secondary efficacy endpoints were not reached, she added.

For patients with inflammatory bowel disease, many will start with a TNF inhibitor, she added. However, if a patient has a psoriasis flare related to TNF inhibition, which may occur in about 30% of patients with underlying Crohn’s disease or a rheumatologic indication, an inhibitor of IL-23 may be warranted — in particular, ustekinumab, which has an indication in moderate to severe active Crohn’s disease, she said.

Early Treatment Important for this Heterogeneous Disease

Psoriatic arthritis is a very heterogeneous disease linked to an array of disorders including synovitis, dactylitis, enthesitis, and spondylitis, Callis Duffin said in her presentation.

“It’s very important for dermatology to be looking for this, because 30% of psoriasis patients have manifestations of it,” she told attendees. “With biologics, you have to be thinking about these phenotypes as you move forward.”

Early diagnosis and treatment of psoriatic arthritis are important because of fairly strong evidence suggesting that delayed diagnosis increases the likelihood of joint destruction, she said.

In one key study, Haroon and colleagues found that delays as short as 6 months from the onset of symptoms to first rheumatologist visit contributed to poor outcomes. In regression analysis, delayed visits were linked to the development of peripheral joint erosions, with an odds ratio of 4.25 (P=0.001), and to worse health-related quality of life, as measured by the Health Assessment Questionnaire, with an odds ratio of 2.2 (P=0.004).

Callis Duffin reported financial relationships with Amgen, Abbvie, Celgene, Lilly, UCB, Novartis, Sienna, Ortho-Dermatologics, Pfizer, and Janssen.

  • Primary Source

    American Academy of Dermatology

    Source Reference: Callis Duffin K “How psoriatic arthritis affects choice of biologics” Presented at the annual meeting of the American Academy of Dermatology, March 1-5, 2019, Washington, D.C. Presentation F042.

  • Secondary Source

    Journal of Psoriasis and Psoriatic Arthritis

    Source Reference: Singh JA, et al “2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis” J Psoriasis Psoriatic Arthritis. 2018 Nov 30.

  • Additional Source

    Annals of the Rheumatic Diseases

    Source Reference: Haroon M, et al “Diagnostic delay of more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis” Ann Rheum Dis 2015; 74(6): 1045-1050.

  • Arthritis & Rheumatology

    Source Reference: Coates LC, et al “Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis” Arthritis Rheumatol 2016; 68(5): 1060-1071.

Psoriatic Arthritis and Biologics: 10 Questions to Ask Your Doctor

Biologic Treatments

Biologics are genetically engineered proteins derived from humans, animals, or microorganisms. Since these drugs are actually formulations of live antibodies, they must be injected subcutaneously or infused intravenously, like a vaccine. Most biologics for psoriatic arthritis can be self-injected, except infliximab, which requires IV infusion.

Some biologics will work within two weeks, but their full effect isn’t typically seen for two to three months. If you don’t respond after being prescribed a TNF inhibitor, your doctor will try a different one. After that, your doctor may try secukinumab or eventually ustekinumab.

Patients may take a biologic on its own or with methotrexate. A new drug, Taltz (ixekizumab), also targets IL-17A, and was approved in March 2016 for psoriasis. Recent clinical trials have suggested it effectively treats psoriatic arthritis as well, but patients should take it with methotrexate to reduce the chances of becoming resistant to ixekizumab.

Each biologic has a different schedule:

  • Humira (adalimumab) is typically injected once every two weeks or weekly.
  • Enbrel (etanercept) is injected once or twice a week.
  • Remicade (infliximab) is delivered via three intravenous infusions at a doctor’s office during the first six weeks of treatment. After this, individuals receive one infusion every six to eight weeks.
  • Simponi (golimumab) is a once-a-month injection.
  • Cimzia (certolizumab pegol) is injected every two weeks for the first three doses and then every two or four weeks continuously.
  • Cosentyx (secukinumab) is injected once a week for five weeks. After this, individuals receive an injection once every four weeks.
  • Stelara (ustekinumab) is an injection first given in two doses, with one initial dose followed by another four weeks later. Then the schedule is once every 12 weeks.
  • Taltz (ixekizumab) starts with two injections that are followed by an injection every two weeks for 12 more weeks. After that, injections are once a month.

What Are the Risks?

Some of the more common side effects with these biologics include upper respiratory infections, reactions at the injection site, and headaches. Depending on the biologic, you might also experience a rash or urinary tract infection, cold symptoms, diarrhea, abdominal pain, or fatigue.

“The risks of using these drugs are mainly thought to revolve around an increased risk of mild to serious infections, including tuberculosis and some fungal infections,” Margolies says.

Anyone taking biologics will undergo monitoring, which usually means an annual blood count and liver tests, but biologics aren’t appropriate for all patients. Individuals with active infections or a significantly compromised immune system should not take biologics. Patients with heart failure or multiple sclerosis (MS), or with a first-degree relative with MS, should not take the TNF inhibitors, but can take secukinumab or ustekinumab.

More serious but very rare side effects can also occur, including nervous system disorders, heart failure, blood disorders, or a syndrome similar to lupus. Infliximab and golimumab carry a very low risk of causing liver damage, and infliximab, golimumab, and ustekinumab have been linked to a small increased risk of cancer. A relapse of hepatitis B may occur with some biologics, too.

Talking to Your Doctor

These are the major questions you will want to discuss with your doctor:

  • Why do you think biologics will work for my psoriatic arthritis?
  • Why do you want to try this specific biologic first?
  • What are the side effects and more serious risks of this particular biologic?
  • How long will it take before I start seeing the effects of the treatment?
  • How will this drug be administered — subcutaneous injection or intravenous infusion?
  • How often will I get this drug?
  • Do I have any health issues that mean I shouldn’t take this medication, or that I have a higher risk of side effects?
  • Can I breast-feed, become pregnant, or attempt to conceive while taking this medication?
  • How much will this drug cost me?
  • What are my next options if this drug doesn’t work?

Internists are in a pivotal position to not only improve psoriatic arthritis symptoms but prevent the progression of the disease and its resulting joint damage, thanks to new drug therapies and more information on early diagnosis, patient education, treatment, and referral.

Because joint damage with psoriatic arthritis can occur in as little as six months, the sooner the various presentations of this complex chronic, inflammatory musculoskeletal disease are recognized and treatment is set in motion, the more likely it is that the new therapies will make a difference.

Patients with psoriatic arthritis should not only see their rheumatologist every two to three months but should also see their internist regularly to monitor potential side effects of medications such as skin infections, urinary tract infections, pneumonia, bronchitis, tuberculosis, and Crohn’s disease. Image by kudryavtsev

But internists used to having few options may not be thinking of psoriatic arthritis. “In the past if we didn’t make the diagnosis there wasn’t much to do about it anyway,” said Mark Lebwohl, MD, Waldman Chair of Dermatology at the Icahn School of Medicine at Mount Sinai Health System in New York and author of an In the Clinic section on psoriasis published in the April 3, 2018, Annals of Internal Medicine.

“Now we can prevent the progression of joint disease … and the internist is the first doctor patients see complaining of joint pain,” he said.

More options available

The recently published 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis recommends using tumor necrosis factor inhibitor (TNFi) biologics as first-line therapy for treatment-naïve patients with active psoriatic arthritis rather than disease-modifying antirheumatic drugs (DMARDs) or oral small-molecule drugs, unless they are contraindicated or the patient prefers an oral medication or is concerned about specific side effects. The new therapies are based on better understanding of underlying immunopathogenesis and cytokine signaling, said Abhijeet Danve, MBBS, MD, FACP, rheumatologist and assistant professor of clinical medicine at Yale School of Medicine in New Haven, Conn.

According to the National Psoriasis Foundation, up to 30% of the more than eight million Americans with psoriasis will develop psoriatic arthritis. While psoriatic arthritis can start at any age, it often appears between ages 30 and 50 years and usually within 10 years after psoriasis begins; about 85% of patients with psoriatic arthritis may have psoriasis first. Some patients present with joint pain first.

As a systematic inflammatory condition, psoriatic arthritis is associated with significantly increased risk of cardiovascular disease, including myocardial infarction and stroke, diabetes, hypertension, and metabolic syndrome. Thus, internists can play a critical role in promptly identifying and treating these comorbidities by advising lifestyle modifications and pharmacotherapy, Dr. Danve said.

“The role for the internist now is more important because early diagnosis matters,” said Dr. Lebwohl.

Making the diagnosis

Psoriatic arthritis can be challenging to diagnose and treat because of its heterogeneous presentation, which can then be complicated by other conditions such as irritable bowel disease or diabetes, said the guideline. According to the National Psoriasis Foundation, up to 15% of people being treated for psoriasis could have undiagnosed psoriatic arthritis.

“We are missing many patients with psoriatic arthritis,” said Siba Raychaudhuri, MD, FACP, professor of rheumatology, dermatology, and immunology and rheumatology program director at the University of California, Davis. “Those untreated patients may irreversible joint damage.”

There are some clues and screening strategies. First, psoriasis—which internists often feel comfortable managing—is a red flag, said Ana-Maria Orbai, MD, MS, director of the psoriatic arthritis program and assistant professor of medicine at Johns Hopkins Medicine in Baltimore.

Psoriasis should tip physicians off to early onset of vascular disease and systemic inflammation, said Nehal N. Mehta, MD, chief of the section of inflammation and cardiometabolic diseases at the National Heart, Lung and Blood Institute in Bethesda, Md. “Physicians attribute fatigue and back pain to arthritis,” he said. “They brush it off.”

Experts said other symptoms may include:

Two screening tests that may be helpful are the Psoriasis Epidemiology Screening Tool (PEST) questionnaire and the Early Arthritis for Psoriatic Patients (EARP) questionnaire, said Dr. Orbai. She said the PEST screen is so quick patients can even complete it at home or in the waiting room. Those answering the questions positively have a high probability of having psoriatic arthritis, she said. Or, if administering a screening test is too cumbersome, “A simple musculoskeletal exam to uncover red flags would be sufficient,” she said.

Laboratory and other tests are not able to identify psoriatic arthritis, but they can add to the evidence, said Dr. Orbai. A blood test can exclude rheumatoid arthritis, and an X-ray of the hands and feet can look for a baseline of prior damage consistent with psoriatic arthritis, she noted.

Just making patients aware of psoriatic arthritis can help diagnose it. Otherwise, patients may misconstrue a negative blood test as negative for psoriatic arthritis or attribute their scaly skin to eczema and not follow up with their physician, Dr. Mehta explained.

Treatment options, reality check

Internists may like to treat patients with mild psoriatic arthritis with NSAIDs to reduce pain and swelling, said Dr. Raychaudhuri. However, ideally psoriatic arthritis patients should be treated with the broader goal of preventing joint destruction, so they should be referred quickly, within a few weeks, to a rheumatologist with psoriatic arthritis expertise, he said.

Now that therapies are available to address and even prevent joint damage, internists should be conscious of the six-month window available to start treatment before that damage occurs, said Dr. Orbai. “Even if only one joint , take it seriously,” she said. “If we don’t treat the inflammation, more joints will become involved.”

For example, Dr. Mehta told the story of a patient, a deli owner in his 50s, who had psoriasis and reported that he couldn’t make sandwiches anymore because his fingers were deformed. He had seen physicians for five years and was never told his hand pain could be psoriatic arthritis. Dr. Mehta did a scan and found psoriatic arthritis throughout the patient’s body.

Dr. Orbai said rheumatologists will consider many factors in devising the treat-to-target approach, recommended by the new guidelines, in which treatments are oriented toward achieving a well-defined result. Those include severity of disease as well as the impact on the patient’s quality of life and daily activities, employment, comorbidities, and treatment access issues. The guideline also notes the need to be aware of costs beyond those associated with the new medications themselves, such as traveling to more frequent appointments for monitoring.

While internists may not be making specific drug treatment decisions, knowing the options will help inform their conversations with patients, said Jasvinder A. Singh, MD, MPH, lead author of the guideline and professor of medicine and epidemiology at the University of Alabama at Birmingham.

“Internists may not have used the therapies, but having the providing the scenarios and choices raises interest and excitement … before the patient sees the rheumatologist,” he said.

The guideline recommends starting therapy with TNFi biologics and trying a different one if the first doesn’t work rather than switching to an IL-17 or an IL-12/23 inhibitor biologic agent. Patients with active psoriatic arthritis despite oral small-molecule therapy should switch to a biologic rather than trying a different oral small-molecule drug, the guideline states.

If TNFis don’t work or are contraindicated or if the patient has severe psoriasis, moving to an IL-17 or IL-12/23 biologic is recommended. The guideline details how and when to use specific drugs rather than others based on the patient’s history and other conditions (e.g., an oral small molecule over a TNFi in a patient with frequent serious infections).

However, that trajectory is not always possible. First, as the guideline acknowledges, patients may prefer an oral medication over biologics, which are given as injections or IV infusion, Dr. Lebwohl said.

Second, because some of the newer medications are very expensive, Dr. Danve said insurance companies require him to see if a patient will respond first to an older drug like methotrexate. As a result, Dr. Danve said a patient’s typical trajectory might include a trial of methotrexate, followed by adding a TNFi inhibitor (e.g., etanercept, adalimumab, certolizumab, golimumab, or infliximab). If the patient does not improve, he would switch to a different TNFi before trying an IL-17 inhibitor.

Patients responsive to one TNFi may suddenly find it less effective after a few years. Dr. Orbai said switching often does the trick. “About 60% will respond to the new medication,” she said. Long-term remission is possible, she said, and for those patients she considers reducing medication therapy.

Some patients require a mix of therapies. For example, a patient could be on methotrexate and a biologic as well as a topical treatment to turn off each of the manifestations , Dr. Orbai said. “That can be a bit of a journey.”

To monitor that journey with all the associated risks and benefits of the new medications, Dr. Singh said patients with psoriatic arthritis should not only see their rheumatologist every two to three months but should also see their internist regularly. The internist can monitor the potential side effects of some of the medications, which include skin infections, urinary tract infections, pneumonia, bronchitis, tuberculosis, and Crohn’s disease. Methotrexate increases the risk of liver disease, which needs to be monitored, especially if the patient is taking a statin, Dr. Orbai said. In addition, patients with psoriasis and psoriatic arthritis are at higher risk of fatty liver and cirrhosis because of the disease itself, Dr. Danve said.

Because biologics can increase risk for other conditions, Dr. Orbai said patients need to be up to date on their yearly dermatologic screening, colonoscopy, and vaccines (e.g., flu, pneumonia, and zoster).

The excitement about new drugs for psoriatic arthritis is likely to continue: More drugs are in the pipeline that will be available in the next few years, according to Dr. Lebwohl. “Some of the best drugs are coming,” he said.

Dr. Raychaudhuri said he is very optimistic about research on the use of small-molecule drugs to target intracellular signaling pathways. Because the small organic molecules will act against the cell-signaling system associated with the disease process of psoriatic disease, the drugs are expected to be more efficacious than the conventional synthetic DMARDs and a possible option for patients who cannot tolerate biologics or in whom biologic treatment has failed, he said.

Beyond meds

Because psoriatic arthritis is a multisystem organ disease with implications for other aspects of patient health, internists should monitor for and manage comorbidities, said Dr. Raychaudhuri. He discussed the association of psoriatic arthritis with increased cardiovascular risk, hypertension, depression, and reduced quality of life in a 2012 article in the Journal of Rheumatology.

“We cannot change the psoriatic arthritis but we can … control lipids, optimize blood pressure, increase weight loss, and thus decrease the disease activity of psoriatic arthritis,” said Dr. Orbai.

Internists are also key in addressing smoking cessation. The new guideline notes that smoking reduces the efficacy of biologics and is associated with other negative health impacts. Internists also can address pain management, which can remain a problem even after inflammation from the psoriatic arthritis is adequately controlled, Dr. Danve said.

The guideline recommends patients with active psoriatic arthritis use some type of nonpharmacologic intervention. For example, physical therapy is important for those with psoriatic arthritis in the spine (spondylitis) and for those with tendon damage to strengthen surrounding muscles and maintain range of motion, Dr. Orbai said.

The guideline also said there may be a role for other nonpharmacological interventions, such as massage or acupuncture. Anything that relieves stress, such as mindfulness, can help since stress affects flares of joint pain for some patients, according to Dr. Orbai. Dr. Danve noted that yoga and meditation also may be helpful. While ultraviolet phototherapy can help psoriasis, it does not have a role in treating psoriatic arthritis, noted Dr. Lebwohl.

Depression often accompanies psoriatic arthritis because the condition is chronic and affects daily living, said Dr. Raychaudhuri. While alleviating the psoriatic arthritis may lessen this, so too will psychological support and group therapy, he said. An ideal approach would be a comprehensive total care program that includes exemplary care of joints, skin, and associated comorbidities, he said.

More advice is on its way: The European League Against Rheumatism is updating its psoriatic arthritis guidelines, as is the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, according to Dr. Orbai. And Dr. Singh’s excitement over the new guidelines—and what’s likely to happen sooner rather than later—is palpable.

“With so many treatment options, now effectively put patients into remission just like cancer. It doesn’t mean the disease has gone away, but we can’t find any evidence of while you’re on the medication,” he said. “We haven’t yet figured out a cure, but things might change in my lifetime.”

Paula S. Katz is a freelance writer in the Chicago area.

Additional reading

Lebwohl M. Psoriasis. Ann Intern Med. 2018;168:ITC49-ITC64.

Raychaudhuri SP. Comorbidities of psoriatic arthritis—metabolic syndrome and prevention: a report from the GRAPPA 2010 annual meeting. J Rheumatol. 2012;39:437-40.

Singh JA, Guyatt G, Ogdie A, Gladman DD, Deal C, Deodhar A, et al. Special article: 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Rheumatol. 2019;71:5-32.

Things to consider when taking a biologic

Pregnancy and breastfeeding

Before you try to conceive, it’s important to speak with your rheumatologist about all your arthritis medications, including biologics. Some medications are not recommended to be used during pregnancy, while others may be continued throughout or for part of the pregnancy. Some medications can stay in the body for a period of time after you stop taking them so you may need to stop them a few months before you try to conceive. Some medications are safe to take while you are breastfeeding while others should not be used. If you are thinking of becoming pregnant in the near future or are not using contraception, you should discuss the most appropriate treatment options with your rheumatologist or rheumatology nurse.

If you fall pregnant unexpectedly, contact your rheumatologist immediately for advice.

Travel

You can still travel domestically and overseas while taking a biologic but plan ahead. Talk to your rheumatologist to ensure you have an adequate supply of your biologic to last your trip, as well as advice on managing your medications while travelling. Talk to your rheumatologist about any vaccinations you may need before your trip.

CONTACT YOUR LOCAL ARTHRITIS OFFICE FOR MORE INFORMATION AND SUPPORT SERVICESFor more information: The Australian Rheumatology Association has information sheets on each of the biologics. The sheets cover detailed information about how to take the medication, side effects and precautions. They are available at www.rheumatology.org.au Consumer Medicine Information is available for each medication you are prescribed and include detailed information about the possible side effects and safe usage of the medication. You will usually find it in the medication packet or ask your pharmacis Medicines Line, a telephone service provided by the National Prescribing Service and healthdirect Australia, gives independent information about medicines. Phone 1300 633 424 Monday to Friday 9am to 5pm AEST or visit www.nps.org.auSource:
A full list of the references used to compile this sheet is available from your local Arthritis Office.

Moderate to Severe Psoriasis and Psoriatic Arthritis: Biologic Drugs

Biologics are different from traditional systemic drugs that impace the entire immune system. Biologics only target specific parts of the immune system. The biologics used to treat psoriatic disease block the action of a specific type of immune cell called a T-cell. Or they block proteins in the immune system, such as tumor necrosis factor-alpha (TNF-alpha), interleukin 17-A or interleukins 12 and 23. These cells and proteins all play a major role in developing psoriasis and psoriatic arthritis.

The following are biologics approved for psoriatic disease. Some are approved for psoriasis, psoriatic arthritis or both.

Treatment Comparison Chart

Biosimilar substitution

The National Psoriasis Foundation Medical Board has issued a statement on biosimilar substitution. Read the statement “

Download the Systemic Treatments: Biologics and Oral Treatments booklet “

Tumor necrosis factor-alpha (TNF-alpha) inhibitors

Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), Simponi (golimumab) and Simponi Aria (golimumab) are drugs that block TNF-alpha. TNF-alpha is a cytokine, or protein, that prompts the body to create inflammation. In psoriasis and psoriatic arthritis, there is excess production of TNF-alpha in the skin or joints. That leads to the rapid growth of skin cells and/or damage to joint tissue. Blocking TNF-alpha production helps stop the inflammatory cycle of psoriatic disease.

Interleukin 12 and 23 (IL-12/23) inhibitors

Stelara (ustekinumab) works by selectively targeting the proteins, or cytokines, interleukin 12 (IL-12) and interleukin 23 (IL-23). Interleukins 12/23 are associated with psoriatic inflammation.

Interleukin 17 (IL-17) inhibitors

Cosentyx (secukinumab) and Taltz (ixekizumab) block a cytokine, or protein, called interleukin 17 (IL-17), which is involved in inflammatory and immune responses. Siliq (brodalumab) blocks the receptor of this cytokine, IL-17 receptor A (IL-17 RA) through which IL-17 mediates the inflammatory and immune responses. There are elevated levels of IL-17 in psoriatic plaques. By interfering with IL-17 signaling, Cosentyx, Siliq and Taltz interrupt the inflammatory cycle of psoriasis, which can lead to symptom improvement for many people who take it.

T-cell inhibitors

Orencia (abatacept) targets T-cells in the immune system. T-cells are a type of white blood cell that is involved in the inflammation in psoriasis and psoriatic disease. Orencia inhibits T-cells from becoming activated to reduce inflammation.

Interleukin 23 (IL-23) inhibitors

Ilumya (tildrakizumab-asmn), Skyrizi (risankizumab-rzaa) and Tremfya (guselkumab) work by targeting interleukin 23 (IL-23). This cytokine is linked with inflammation in psoriasis and psoriatic arthritis. Ilumya, Skyrizi and Tremfya work to reduce psoriatic symptoms and slow disease progression.

How are they used?

Biologics are taken by injection or by IV infusion. Cimzia, Cosentyx, Enbrel, Humira, Ilumya, Simponi, Skyrizi, Stelara, Taltz and Tremfya are injected in the legs, abdomen or arms by the patient, a health care provider or a family member. Remicade and Simponi Aria are given through IV infusion in a doctor’s office or infusion center. Orencia can be taken as an injection or by IV infusion.

Biologics are prescribed for individuals with moderate to severe cases of plaque psoriasis and psoriatic arthritis. They are a viable option for those who have not responded to or have experienced harmful side effects from other treatments.

Do not take biologics if:

  • Your immune system is significantly compromised;
  • You have an active infection.

Screening for tuberculosis (TB) or other infectious diseases is often required before starting treatment with biologics.

What are the risks?

Anyone considering taking a biologic drug should talk with his or her doctor about the short- and long-term side effects and risks. It is important to weigh the risks against the benefits of using the drugs.

Biologics can increase the risk of infection. If you develop any sign of an infection, such as a fever, cough or flu-like symptoms, you should contact your doctor right away.

For specific side effect information, download the individual product fact sheet.

Using biologics with other psoriasis treatments

All the current biologics can be used with other treatments such as phototherapy or topicals, though using phototherapy along with Remicade may increase your skin cancer risk.

Cimzia, Enbrel, Humira and Remicade are shown to be safe and effective when taken with methotrexate. Talk to your doctor about whether using any other treatments with a biologic is right for you.

For more information on individual biologics,

Learn the latest in biologics

Anthony Fernandez, M.D., Ph.D., will walk you through the latest news and what’s coming soon in the world of biologics in this informative webinar.

Test your treatment IQ

How much do you know about your psoriatic disease treatment options? Put your knowledge to the test with our treatment quiz and let NPF help you fill in some of the gaps.

Last updated 8/16/19 by the National Psoriasis Foundation.

By: Howard R. Smith, MD

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If you have recently been diagnosed with psoriatic arthritis, your doctor may have told you about a type of medicine that can reverse disease progression, stop damage to your joints – and might even put your disease into remission.

These medicines are called DMARDs, which stands for disease-modifying anti-rheumatic drugs. The drugs work by curbing the body’s out-of-control immune system response that causes psoriatic arthritis.

“DMARDs work by curbing your immune system, and, as a result, reduce inflammation,” says rheumatologist Howard R. Smith, MD.

Doctors often prescribe DMARDs when non-steroidal anti-inflammatories such as ibuprofen or other medications aren’t effective or for patients who have disease that is eroding their joints, Dr. Smith says.

DMARDs fall into two categories, biologic and non-biologic:

Non-biologic DMARDs – These medicines slow the disease process by modifying the immune system. Methotrexate is the most commonly prescribed non-biologic DMARD for psoriatic arthritis treatment. Methotrexate is an effective immune system suppressor and can treat the accompanying psoriasis as well as arthritis.

Biologic DMARDs – Introduced in the late 1990s for treating moderate to severe autoimmune diseases, biologic DMARDS target cells at a molecular level to prevent inflammation at a very early stage. They work by blocking a protein made by the immune system that contributes to psoriasis and arthritis. Biologic DMARDs are given by an injection or infusion into a blood vessel.

Reducing signs and symptoms

Both of these drugs reduce the signs and symptoms of psoriatic arthritis – and most exciting – they also can slow down damage to your joints, Dr. Smith says

“DMARDs slow down psoriatic arthritis and improve quality of life for most people,” Dr. Smith says. “Some patients will even achieve a remission while taking them. But more typically, disease activity continues, but at a slower, less intense rate.”

If your doctor prescribes DMARDs, here, according to Dr. Smith, are three things you should know about these powerful medicines.

1. All DMARDs may have side effects

Because DMARDs are a systemic treatment, they may have side effects, such as stomach upset, liver problems or blood issues, Dr. Smith says. It may take some tinkering for your physician to find the right regimen for you.

Possible long-term complications include liver damage with methotrexate and leflunomide. Some dormant long-term infections such as tuberculosis, can be re-activated by DMARDs.

“DMARDs change your immune system, so you may get more intense viral or bacterial infections. Make sure to let your doctor know about any serious infections,” Dr. Smith says.

You also should check with your doctor before getting any vaccines, Dr. Smith says. “Live vaccines, like the shingles vaccine, may be dangerous with certain of medications,” he says.

Some biologics also have been linked to a very small increased risk of cancer. You should ask your doctor about it, Dr. Smith says.

“Though DMARDs may have side effects, there still is good reason to take them — they’re proven to be effective against psoriatic arthritis,” Dr. Smith says.

2. It may take some time for DMARDs to work

It takes time for a DMARD to change your immune system. It may take months for some of the non-biologics to work. Biologic DMARDs may take a few weeks.

3. You may need to take more than one drug

DMARDs are used alone and in combination with other drugs. It’s also common for a physician to prescribe more than one DMARD. For example, studies show that methotrexate and a biologic may work better together than alone.

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