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Abstract

This activity uses real-world patient examples to help pharmacists understand the needs of patients with psoriatic arthritis (PsA) better. PsA is often undiagnosed and undertreated. Better recognition of PsA and earlier, more aggressive treatment of PsA has been proven to improve outcomes. Traditionally, health care providers have used nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressants, and physical therapy to treat psoriatic arthritis. New treatment options with unique therapeutic targets are now available for PsA. Pharmacists can work with the multidisciplinary team to focus its attention on efficacy, safety, and administration that are compatible with patient preferences. Many patients fail to respond to the first biologic they try, and the reasons for treatment failure among these patients are not completely understood. Emerging strategies for management when treatment failure occurs can help patients find relief from this painful condition. Pharmacists can make recommendations for these patients that will increase their chances of successful treatment and improve their care.

Introduction

Psoriatic arthritis (PsA), a seronegative inflammatory arthritis with a varying clinical presentation, is driven by T cells reacting to antigens presented by macrophages or dendritic cells. It is, as its name implies, associated with psoriasis (see Sidebar) and roughly 6% to 42% of patients with plaque psoriasis develop PsA; the wide range in these statistics reflects a significant problem of underdiagnosis. PsA typically develops approximately 12 years after the first occurrence of psoriatic skin lesions.^1,2 However, 10% of people with PsA develop musculoskeletal symptoms before skin manifestations.^2,3 As with psoriasis, PsA affects men and women equally.¹ PsA most often develops between the ages of 35 and 55 years, although it can occur at any age.

Basic Facts about Plaque Psoriasis Manifests as bilateral symmetrical papules that progress to thick red patches often covered by silvery scales Characteristically located on the elbows, knees, low back, face, palms, and soles of the feet Skin patches, or lesions, may occur suddenly or worsen over time and are often preceded by a recent infection (e.g., strep throat, viral infections including HIV), trauma, or the use of certain medications Skin lesions may be painful, pruritic, and/or red and swollen Nail involvement includes onycholysis (loosening of a nail from the nail bed, usually starting at the border of the nail), pitting, discoloration, and dystrophy Ocular signs and symptoms occur in approximately 10% of those with psoriasis and include redness and tearing Use this picture: https://www.canstockphoto.com/psoriasis-49846131.html The visibility of plaques can cause stress and poor self-esteem, often leading to comorbid depression, anxiety, sexual dysfunction, and thoughts of suicide Increases risk of other immune-mediated comorbid conditions such as Crohn’s disease and ulcerative colitis Patients with family histories of multiple sclerosis are more likely to develop psoriasis Common comorbid conditions include obesity and cardiovascular disease, including myocardial infarctions and ischemic heart disease Sources: reference 4-9

PsA's symptoms can include asymmetric or symmetric joint pain affecting few or many joints with highly irregular patterns of joint and skin involvement and severity.¹⁰ PsA is difficult to characterize, but certain symptoms generally are suggestive of PsA. Up to 93% of patients have nail disease, approximately 50% have enthesitis (muscle, tendon, or ligament irritability where it enters into the bones), and about 40% have dactylitis (painful inflammation of an entire finger or toe, sometimes called sausage digit). Patients most often present with peripheral (oligoarticular or polyarticular) arthritis, and between 7% and 32% of patients have psoriatic spondylitis.¹¹ As systemic inflammation and extensive synovitis develop and persist, articular cartilage erosion and joint destruction follow.^12,13 Its prevalence is difficult to estimate,¹⁴ but statisticians believe that in the United States (U.S.), 0.06% to 0.25% of the population is affected.¹¹

Health care providers need to be concerned about this patient population for several reasons, many of which are obvious in pharmacy settings. Patients with PsA generally have poor long-term outcomes, diminished quality of life, increased disability, and comorbidities (e.g., type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease).¹⁴ This disease's costs are high.¹⁵ Compared with patients without psoriasis or PsA, affected patients have total health care costs that are considerably higher ($27,123 versus $5,301 annually). Pharmacy costs consume a good portion of the elevated cost, and are approximately $18,083 annually as opposed to $1,267 annually in other patients.¹⁶

Patients with PsA experience many challenges. The disease and its visible and invisible symptoms contribute to distress, productivity deficits, work absenteeism, and physical limitations.^3,17 Patients with concurrent psoriasis and PsA report significantly lower quality of life (QoL) and more depression and anxiety compared with patients without joint symptoms.^18,19

Early diagnosis and appropriate therapy can prevent joint destruction, highlighting the fact that diagnostic delay has been associated with suboptimal outcomes. Clinical research has demonstrated that patients presenting with established disease tend to have marked clinical disease progression.^2,20,21 Individuals with a disease duration exceeding 2 years at referral were more likely to be older, have more joint damage, and were less likely to be on disease modifying anti-rheumatic drugs (DMARDs). Delays of as little as 6 months to 1 year from symptom onset to diagnosis are associated with poorer physical function.²²

Increased awareness of PsA and its treatment could lead to earlier intervention and improved patient outcomes.^20,23

Screening

Two facts, when looked at side-by-side, indicate 1 way to screen for PsA:

• Approximately 2% of the US population has psoriasis, which makes it a common condition²⁴
• Most patients with PsA develop skin manifestations prior to joint symptoms²⁴

This highlights a simple way to screen: routinely ask all patients with psoriasis if they have joint pain or musculoskeletal manifestations. Guidelines now reflect this intervention. The National Institute for Health and Care Excellence (NICE) recommends clinicians assess patients who have any type of psoriasis annually for PsA.²⁵ Yet screening rates remain low.³ In a study of 1,511 patients with psoriasis, 312 patients had PsA, with 85% of them undiagnosed prior to the study.²⁶ Another study found that 41% of patients with psoriasis (N = 949) had undiagnosed PsA.²⁷ Patients with psoriasis are frequent visitors at the pharmacy, and pharmacists can use those visits to heighten awareness of PsA and hasten diagnosis.

Pharmacists can refer patients who have concurrent psoriasis and joint pain to their primary care providers, dermatologists, or rheumatologists. In a report based on surveys of patients with psoriasis or PsA, 22% of patients were treated by a primary care provider and 78% by a dermatologist or rheumatologist.²⁸ Another study found that approximately 10% of patients with PsA were treated by general practitioners or internists with roughly 83% treated by a dermatologist and/or rheumatologist; the remaining 7% were not under a physician's care.²¹

In terms of formal tools, many clinicians use the Classification of Psoriatic Arthritis (CASPAR) screening algorithm most to diagnose PsA because its specificity and sensitivity are 99.1% and 87%, respectively. Other screening tools include questionnaires, which include the Psoriatic Arthritis Screening and Evaluation (PASE)²⁹; the Toronto Psoriatic Arthritis Screen II (ToPAS II)³⁰; the Psoriasis Epidemiology Screening Tool (PEST)³¹; and the Early Arthritis for Psoriatic Patients (EARP).³²

PsA's pathophysiology, which is irrevocably entwined with psoriasis, is complex. Until recently, researchers have been ignorant of its origins and the way in which it progresses. With no animal model for research, researchers relied on clinical studies and translational science.³³ Now, we know that once triggered, immune modulators and inflammatory components activate psoriasis. Specifically, leukocytes recruit T-cells in the epidermis, resulting in keratinocyte proliferation. Cell cycle turnover increases from 23 days to 3 to 5 days and creates the characteristic hyperproliferative skin lesions.^7,33 Activation of the inflammatory process leads to production of an assortment of cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12), and pro-inflammatory mediators such as IL-17 and IL-23.³⁴ Enhanced understanding of these processes has allowed researchers to develop biologics that target the underlying pathophysiology. Unfortunately, biologics remain underused, especially in patients with moderate to severe disease. Although biologics have been FDA-approved for psoriatic arthris since 2002, by 2013 only less than 5% of patients with PsA reported using biologics. Overall, 45.5% of patients with PsA report dissatisfaction with their treatments.³⁵

Risk factors

Psoriasis and PsA tend to run in families, suggesting a strong genetic basis in both disorders. PsA's prevalence among first-degree relatives is 49 times higher than the prevalence in the general population.³⁶ Advanced genetic testing has identified 25 gene variants, with the autosomal dominant human leukocyte antigen Cw6 closely associated with psoriasis, that increase the risk of a patient developing psoriasis.^4,7

In addition to preexisting psoriasis, certain factors increase risk of PsA. Some studies suggest having psoriasis over a greater body surface area is associated with an increased risk of developing PsA. However, the extent and severity of psoriasis do not correlate with the severity of PsA joint disease.^1,26

Research has linked specific psoriasis symptoms with PsA risk, including scalp lesions (increase risk 3.75 times); nail dystrophy (increase risk 2.24 times), and intergluteal (between the buttocks) or perianal lesions (almost doubles the risk). Nail bed damage is an important indicator of disease for a good reason. Anatomically, the nail is linked to the connective tissue between the bone and tendons or ligaments; fibers run from the extension tendon and the collateral ligament of the distal interphalangeal joint. Tissue-specific factors, including microtrauma and biomechanical stress, appear to cause aberrant innate immune responses and persistent inflammation. This process links nail changes in psoriasis with enthesitis and PsA's joint involvement.^37,38

Individuals who have psoriasis and high body mass index are at higher risk of PsA. TNF inhibitors for psoriasis may be less effective in obese patients.^39,40

Case Study

Sandy is a 54-year-old slightly obese woman who has had prescription medication filled for moderate psoriasis for approximately 20 years. She reports that she probably had psoriasis earlier than that because in her 20s she frequently had "problem skin" that was worse in the cold dry weather and improved if she moisturized frequently. Today, she's at the pharmacy asking for a recommendation for something to deal with stiffness and pain. She says that she thinks she's developing arthritis like her parents had, and she’s surprised that it's starting so early in her life.

You began by asking about the nature and duration of the pain. She shows you that the pain is located primarily in the distal joints of her fingers and wrists, which appear swollen. You ask if she has any problems in her feet or legs, and she says yes, “It's similar to the pain in my hands and wrists.” When you press for more information about the type of pain, Sandy says that her skin is tender to the touch, and she feels swollen under her skin in the affected areas. She also says it's a throbbing pain. When you ask her, "Is there any time during the day when it's more painful?" She replied by saying, "Honestly, when I wake up in the morning I'm still really tired. I just don't want to get out of bed and I'm stiff until around noon." She has perfectly manicured fingers, so you can't see any nail changes. But when you ask where she has her manicures done and how often, she says, "Oh, I go to this little place down the road, but I'm thinking about stopping. I think I have a fungal infection because my nails are starting to separate from the nail bed." She reports that on a scale of 1 to 10, the pain in her joints is at about a 5.

Case Analysis

It's possible and perhaps likely that Sandy is developing PsA. She is showing signs of its characteristic inflammation, stiffness, and pain in and around the distal joints of the fingers, toes, wrists, ankles, and knees. And, although she thinks she may have a fungal infection, it may be an early sign of nail dystrophy.^4,7 Her many years of dealing with psoriasis is a risk factor. The Classification Criteria for Psoriatic Arthritis (CASPAR; Table 1) is used to diagnose PsA with high sensitivity and specificity.⁴¹

Sally will probably have additional questions, and the most important step to take is to explain her risk for PsA. The initial diagnosis (or suggestion of this diagnosis) can be startling and emotionally challenging for patients. At this point, it's important to assure her that with early and aggressive treatment, PsA can be managed (but not cured). The first step is referral to her primary care provider (PCP) or dermatologist if she has one, but many patients see rheumatologists for their PsA. All of these providers are capable of treating PsA, but specialists may be more aggressive,

As noted, PsA is a seronegative arthritis. Unlike rheumatoid arthritis, wherein rheumatoid factor can be measured and elevated levels support the diagnosis, PsA has no serum marker. Diagnosis is made pursuant to physical exam, observation, and the process of elimination. Most rheumatologists will perform MRIs and x-rays of symptomatic joints. Patients often report symptoms that are similar to the 3 other arthritic diseases (e.g., rheumatoid arthritis, gout, and reactive arthritis). PsA, however, is not associated with rheumatoid arthritis's bumps under the skin. Comorbid rheumatoid arthritis and PsA is rare, but comorbid gout and PsA is possible. In addition, individuals who have PsA can have elevated uric acid levels with no gouty symptoms.¹

Treatment

PsA occurs over a range of severities, with some patients reporting mild symptoms and others progressing to the severe form. The treating clinician will consider the number of joints affected as the basis for the treatment plan. Patients who have 4 or fewer joints involved are diagnosed with oligoarticular (or mild) PsA, which is usually asymmetric. Once more than 4 joints are involved, the clinician will consider the PsA to be moderate to severe, and refer to it as polyarticular. Polyarticular PsA is usually symmetric. In addition, the treating clinician will look for the particular sites affected, referred to as domains. Currently, clinicians assess 5 PsA domains: skin, peripheral, the axial disease, dactylitis and enthesitis. Table 2 lists the characteristic symptoms in which PsA may be present and recommended initial treatment.

Case Study

Sandy sees her PCP and begins treatment with around-the-clock prescription strength  NSAIDs, and systemic corticosteroids when she experiences a flare. Within the first month, she reports significant improvement. She says that she has considerably less pain although it still fluctuates. When you are on duty and she visits for prescription refills, you tend to check with her but several months go by and you don't see her. Nine months later, she comes to the pharmacy and looks visibly worn. She reports that the pain has worsened. She also says that she has been taking a proton pump inhibitor regularly because she's had an upset stomach, and she often skips her NSAID because she thinks it contributes to the problem. During your gentle questioning, she reports that she has not seen her PCP or any other provider since starting prescription strength NSAIDs. When you indicate that seeing her PCP or even a specialist every 3 months is a good plan, she seems surprised.

Case Analysis

Traditionally, clinicians have prescribed NSAIDs and local corticosteroid injections, reserving DMARDs for NSAID-resistant cases. Once treatment begins, it's important for patients to schedule and attend regular office visits. Patients who have mild disease benefit from seeing their prescribers every 3 months. If disease activity is high, patients may need to be seen monthly. Patients need routine screening for adverse effects and lab work. Even NSAIDs can cause significant adverse events (e.g., impaired kidney function, gastrointestinal distress, and increase risk of heart attack or stroke) in patients and need to be monitored for new or developing adverse reactions. Sandy's PCP has followed the general treatment paradigm used for several decades, but it's rapidly becoming an obsolete standard of care and there are 2 problems here.

First, the PCP has not conducted any outreach to determine if Sandy is responding well or to monitor. Busy clinicians frequently fail to schedule follow-up visits or make outreach calls. Second, Sandy seems to be unaware that she should return to the PCP or be referred to dermatologist or a rheumatologist if her symptoms fail to improve or worsens. She also seems to be unaware of the need for self-management. Findings that 40% of patients may develop erosive and deforming arthritis have led to recommendations of early treatment with DMARDs in patients with active PsA. In addition to older DMARDs, U.S. Food and Drug Administration (FDA) has approved numerous biologic agents and targeted synthetic agents for PsA. Asking, "When was the last time you saw your prescriber?" can lead to some productive discussion and a referral back to the prescriber.⁴³

Sandy could also benefit from physical and occupational therapy, which most guidelines recommend early in the disease process. Each patient will need an individualized exercise regimen, and in fact, each patient's physical therapy prescription will change as his or her disease phase changes.^42,43

While this activity focuses on PsA, pharmacists need to be aware of the various treatment modalities for psoriasis so they can screen for development of PsA in affected patients. Guidelines for the management of psoriasis include the American Academy of Dermatology (AAD), Canadian Dermatology Association, and National Institute of Health and Care Excellence.^8,44,45 Clinicians have great interest in and patients often use some nonpharmacologic treatment modalities (e.g., acupuncture, smoking cessation, vitamin D supplementation, and weight loss), but evidence for these options is scant. Pharmacologic agents remain the cornerstone of treatment.⁴⁶

Especially when biologics were first introduced in 2004 and in the few years after, health systems and insurers tended to reserve them for moderate to severe psoriasis and PsA (Table 3).^47,48 Their use has increased because they target the underlying pathophysiologic process associated with both psoriasis and PsA. Biologics are classified by mechanism of action: TNF-alpha inhibitors (adalimumab, etanercept, and infliximab) and IL inhibitors (ustekinumab, ixekizumab and secukinumab).⁴⁵

For pharmacists to help patients with PsA, they must be familiar with treatment options and expectations associated with treatment. The European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) released PsA treatment algorithms in 2015. They both include NSAIDs and glucocorticoids in early treatment or for mild disease followed by DMARDs such as methotrexate (MTX), leflunomide, or sulfasalazine and then tumor necrosis factor–alpha (TNF-alpha) inhibitors based on patient-specific factors such as previous treatment failure, severity, and domain involved.^42,43 The primary PsA treatment goal is disease remission or low disease activity as measured by inflammation, pain, and joint function. Several studies indicate that physicians tend to overestimate remission and low disease activity in PsA patients when compared with disease activity indices. Also patients' and clinicians' perceptions of response or failure are often misaligned.^62,63

Several of PsA’s characteristics complicate treatment selection. Medications used to treat PsA sometimes produce uneven response in different manifestations; some are more effective for skin and others more effective for joints. So, clinical care and treatment of PsA is a complex process that balances disease activity with medication risks and benefits and patient priorities.^15,64 Head-to-head studies have failed to identify significant differences between most agents and limited information is available demonstrating effectiveness for PsA’s various manifestations. Patient preferences and safety issues must drive treatment selection. Patients will have strong preferences for route of administration, which can influence adherence to treatment.⁶⁴ Safety, contraindications, and comorbid conditions such as congestive heart failure, systemic lupus erythematosus, multiple sclerosis, tuberculosis, and history of infection also influence treatment decisions.^42,64

Familiarity with each agent’s dosing and administration can help patients decide between self-administered subcutaneous options or intravenous administration in a health care clinic.⁶⁴ PsA’s unpredictable clinical course often means that patients need multiple trials of various drugs and biologics. Adherence is also a challenge, as psoriasis itself is labor intense, requiring frequent application of creams and emollients, and systemic treatments that have adverse effects. Adding treatment for joint pain complicates the picture. Pharmacists need to provide proper counseling that includes indications and appropriate use of each prescribed and over-the-counter drug, reasonable expectations, and cost of therapy.

Clinicians often prescribe MTX and other conventional DMARDs despite only scant supporting evidence of efficacy from clinical trials.^3,43 Many patients with PsA are candidates for biologic treatment if they do not respond to or cannot tolerate initial treatments.^42,43 PsA is heterogeneous, and depending on which domain is involved, a case can be made for using biologics very early in a patient’s treatment strategy (see Table 2).⁴³ Guidelines tend to recommend TNF-alpha inhibitors based on long-term experience, established safety, and efficacy profile.⁴² However, there are instances where TNF-alpha inhibitors would not be the most appropriate initial biologic choice, such as in patients with comorbidities or a history of infection.⁴²

The most recent updates to guideline recommendations include new agents with unique mechanisms of action.^42,43

Case Study

Sandy sees her dermatologist, who discontinues the NSAIDs and puts her on MTX. Unfortunately, she cannot tolerate the MTX and develops nausea, profound fatigue, and gastrointestinal problems. Immediately, he switches her to adalimumab. Sandy, her dermatologist, and the other members of her health care team revisit treatment goals: disease remission or low disease activity as measured by

• inflammation
• pain, and
• joint function

After 4 months, Sandy comes to the pharmacy and the pharmacist asks if she is more satisfied with treatment. She says, “I haven’t noticed any improvement since I began adalimumab. Is there anything else I can try?”

Various guidelines recommend specific treatments for PsA, but while they are similar, they differ in small ways. The 2015 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis guidelines recommend treatment options based on clinical presentation (e.g., skin and nail disease, dactylitis), but the AAD guidelines recommend treating by disease severity. An American College of Rheumatology/National Psoriasis Foundation Guideline for PsA has recently been developed and is different from previous guidelines in the following ways:^65,66,67

• In treatment-naive patients with active PsA, the guidelines are expected to recommend a biologic TNF inhibitor over conventional DMARDs as a first-line option rather than an initial trial of conventional DMARDs.
• The guideline incorporates patients’ opinions extensively and encourages informed discussions between patients and their health care providers.
• With a limited number of randomized controlled clinical trials, the guideline allows a fair amount of flexibility when choosing treatments.

In general, the guidelines recommend treating mild PsA with NSAIDs, and progressing to nonbiologic (MTX, leflunomide, and sulfasalazine) and biologic DMARDs in moderate to severe PsA. As noted, guidelines are beginning to recommend biologics and drugs with new mechanisms of action earlier. Table 3 lists the currently approved biologic DMARDs that are FDA-approved for both psoriasis and PsA, and notes which indications each agent carries.⁶⁸ Note that the approved TNF inhibitors carry boxed warnings for increased risk of serious infections leading to hospitalization or death, including tuberculosis, bacterial sepsis, invasive fungal infections (e.g., histoplasmosis), and infections because of other opportunistic pathogens. The boxed warning also reminds prescribers that lymphoma and other malignancies have been reported in some patients. Patients using any of the biologics should avoid live vaccines. Note that most of these products also require the pharmacist to give the patient a Medication Guide.^49-61 New treatment options, such as agents targeting interleukin (IL) 12/23, IL-17, and phosphodiesterase 4 (PDE4), are also now included in the guidelines.

Apremilast, an oral phosphodiesterase 4 inhibitor, helps improve joint pain and swelling. This drug is initiated at 10 mg on the morning of day 1, and then up-titrated over 6 days to 30 mg twice daily.^54,68 It achieved significant improvement in the percentage of patients with 20% improvement in the American College of Rheumatology score (ACR20) over placebo (41% versus 18%; P less than or equal to 0.0001) and Health Assessment Questionnaire-Disability Index score (-0.20 versus -0.07; P = 0.0073) in a clinical trial.⁶⁸ Patients with renal failure generally take 30 mg once daily. Apremilast’s most common adverse effects include diarrhea, nausea, and headache. It should not be given concurrently with strong CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin).⁵⁴

Tofacitinib is an oral Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes that transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane. This leads to effects on hematopoiesis and immune cell function in the cell. Tofacitinib interrupts the JAK signaling pathway, preventing the phosphorylation and activation of Signal Transducers and Activators of Transcription.⁶⁹

Patients who have PsA had ACR20 response rates of 50% with tofacitinib 5 mg and 47% with 10 mg, compared with response rates of 24% with placebo in patients who had an inadequate response to TNF-alpha inhibitors (P less than 0.001).⁷⁰ Concurrent use of biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine with tofacitinib is not recommended. Patients with PsA generally take 5 mg twice daily, or 11 mg of the extended release formulation once daily. Dose adjustments are needed in patients with moderate or severe renal impairment or moderate hepatic impairment; lymphopenia, neutropenia, or anemia; or those taking CYP2C19 and/or CYP3A4 inhibitors. Tofacitinib’s most common adverse effects (alone or in combination with DMARDs) include upper respiratory tract infection, nasopharyngitis, diarrhea, and headache. This drug has a boxed warning concerning the potential for serious infection (bacterial, viral [including herpes zoster], and opportunistic) and lymphoma. Patients may experience dose-dependent increases in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Clinicians should monitor these levels 4 to 8 weeks after starting tofacitinib. All patients need to be screened for tuberculosis before starting tofacitinib.⁶⁹

For Sandy, a change in medication is warranted. It’s possible that she will need to try more than 1 alternative treatment. Since a TNF inhibitor has not worked, selecting an agent with a different mechanism of action is reasonable. A recent study using a database identified 1,235 patients with psoriatic arthritis. The majority of patients with PsA discontinued their index biologic (TNF inhibitor or anti-IL-12/23 inhibitor) within a year. Nearly half of patients started an adjunctive medication (generally analgesics and conventional anti-inflammatory medications),⁷¹ so Sandy’s situation is not unusual. In that same study, approximately 23% of patients switched to a different biologic.⁷¹

Again, patient preferences and screening for contraindications is important. Sandy has not responded to adequate trials of at least 2 DMARDs; an adequate trial of a TNF-alpha inhibitor is 12 weeks, and she is not responding. Several options remain, and the guidelines usually recommend them in this order:

• She can try an IL-17 inhibitor like secukinumab or ixekizumab. They selectively bind to IL17A and in doing so, prevents it from binding to its receptors and causing inflammation.
• Ustekinumab is another option, as it is an IL-12 and IL-23 inhibitor.
• Apremilast and tofacitinib are oral options that are a phosphodiesterase 4 inhibitor and a JAK inhibitor respectively.

Case Study

Sandy switches to infliximab, and within a month or 2, she sees improvement. She is able to return to the exercise classes she discontinued before starting adalimumab, and she has more energy. She sees her prescriber every 3 months, and at the third visit, she indicates that her pain is increasing. In addition, she has had repeated episodes of sinusitis. She’d like to stop the infliximab, and she is discouraged. She says, “I think I just need to use NSAIDs and cortisone injections when things get too painful. These fancy new medicines are not working for me!”

Guidelines that specifically address switching therapy were developed when only 1 class of biologics—TNF inhibitors—were available. Drugs or biologics with different mechanisms of action weren’t approved yet. They recommended switching patients who failed to respond to 1 TNF inhibitor to a second.⁷² However, recent treatment recommendations for PsA include conditional recommendations based on observational studies; they suggest switching to an alternative biologic with the same or a different mechanism of action if patients do not respond to a biologic therapy.⁷³ Large-scale randomized controlled trials of secukinumab and ustekinumab showed that responses were significantly improved compared with placebo in patients who failed to respond to 1 or more TNF inhibitors. All of these agents inhibit radiographic disease progression.^{69,71,7272,74,75} However, the onset of action for ustekinumab is slower than that of TNF inhibitors in patients with PsA. Further, an increase in the number of TNF inhibitor exposures or failures correlates with poorer response to subsequent ustekinumab therapy.⁷² This suggests that patients who do not respond to biologic DMARD therapy may be afflicted with a different (and yet to be identified) phenotype or develop an altered immune response.

Conclusion

Sally’s journey from moderate psoriasis to active PsA is typical. She possesses many of the risk factors associated with PsA, and at this point, she may consider a trial of secukinumab or ustekinumab if properly counseled. Fortunately, if she doesn’t respond to these IL inhibitors, 2 oral agents are also currently FDA-approved and have different mechanisms of action. In addition, a number of new agents are in the development pipeline. These include briakinumab, risankizumab, guselkumab, and tildrakizumab.⁷⁶

Sally and patients like her need support and encouragement from their health care teams. Pharmacists need to help patients focus on reducing inflammation and pain, and increasing joint function. Patients also need to have reasonable expectations, and pharmacists need to counsel patients thoroughly can manage those expectations. This is an exciting time in PsA research and treatment, as never before have patients with PsA had so many options that actually prevent disease progression. Employing these tools—medication, counseling, and teamwork—early and aggressively can improve outcomes.

References

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