- Daus, Linda
- Elliott, Emily
- Young, Melodie
ABSTRACT: Psoriasis is a chronic disease marked by relapses and remissions. Further, patients with psoriasis demonstrate interpatient and intrapatient variability in response to therapy. Biologic therapies have significantly changed psoriasis management. Although most patients respond to a biologic therapy, response varies between patients and even within individual patients over time. Patients eligible for biologic therapy who fail to achieve adequate disease control should be considered for a course of an alternative biologic therapy. Because of their unique mechanisms of action, failure to respond to one biologic or class of biologic therapies does not eliminate the possibility of successful treatment with another. Dermatology nurses play a vital role in identifying and managing patients with inadequate response. Assessing patient response and satisfaction on a regular basis is an important element of psoriasis management. Treatment guidelines and clinical practice tools have been developed to guide therapeutic selection and monitor patient response for optimal long-term management of patients.
Historically, the treatment of psoriasis has involved the conventional systemic drugs cyclosporine, methotrexate, and acitretin; psoralen-ultraviolet A and ultraviolet B (UVB) phototherapies; and topical therapies. Biologic systemic agents are relatively new, and they fall into two main categories based on markedly different mechanisms of action: tumor necrosis factor (TNF) antagonists and T-cell modulators. TNF antagonists block inflammatory responses by preventing the binding of TNF[alpha] to its receptor, whereas T-cell modulators inhibit multiple T-cell-mediated steps central to the pathogenesis of psoriasis. Three TNF antagonists are currently approved for treatment of plaque psoriasis: etanercept, infliximab, and adalimumab. Two T-cell modulators, alefacept and efalizumab, are approved and are available for the treatment of moderate to severe plaque psoriasis.
Two surveys administered by the National Psoriasis Foundation have found that daily activities such as sleep, sexual activity, job duties, and use of the hands are adversely affected in patients with psoriasis (Gelfand et al., 2004; Horn et al., 2007a, 2007b; Krueger et al., 2001; Stern, Nijsten, Feldman, Margolis, & Rolstad, 2004). In addition to its physical manifestations, psoriasis also has a profound emotional and social impact on quality of life (Krueger et al., 2001). Unfortunately, clinical practice patterns have not kept pace with pharmacological breakthroughs. Despite treatment guidelines suggesting the use of systemic therapy or phototherapy for patients with moderate to severe psoriasis, and the recent approval of biologics for psoriasis treatment, only 37% of patients with severe disease and 20% of patients with moderate disease received either traditional or biologic systemic therapy (Horn, Patel, Fox, & Dann, 2007). A survey conducted by the National Psoriasis Foundation (2006) found that many patients with moderate and severe psoriasis were not being treated in accordance with published therapeutic guidelines. Less than one third (29%) of respondents to this survey were very satisfied with their psoriasis treatment (National Psoriasis Foundation, 2006). Overall, many patients feel that their clinicians fail to appreciate the impact of their disease and that they are being undertreated (Horn et al., 2007a; Krueger et al., 2001; Stern et al., 2004).
VARIABLE PATIENT RESPONSE
Patient response to psoriasis therapy is highly variable. Clinical studies have demonstrated that 12% to 50% of psoriasis patients respond inadequately to anti-TNF therapy, which is defined as either failing to respond initially or losing response over time (Gordon, Langley, et al., 2006; Papp et al., 2005; Reich et al., 2005). In a study assessing clinical response to adalimumab, 76% (34/45) of patients receiving adalimumab every other week and 88% (44/50) of patients receiving adalimumab weekly achieved 50% reduction in the Psoriasis Area and Severity Index (PASI-50) at 12 weeks; 53% (23/45) and 80% (40/50) of patients, respectively, achieved 75% reduction (PASI-75) at 12 weeks. At 60 weeks, PASI-50 rates dropped to 64% (every other week) and 66% (weekly), whereas PASI-75 rates decreased to 56% (every other week) and 64% (weekly; Gordon, Langley et al., 2006). Another Phase 3 trial, which investigated the efficacy and safety of etanercept, found that, at 12 weeks, PASI-50 was achieved by 77% (150/194) and PASI-75 was achieved by 47% (91/194) of patients receiving etanercept twice weekly (Papp et al., 2005). The outcomes of both clinical trials represent great improvements in severity of psoriasis symptoms. However, each trial demonstrated a percentage of patients with inadequate responses to the selected treatments. Furthermore, 12% to 25% of patients treated with anti-TNF therapy were nonresponders who failed to achieve PASI-50 by Weeks 12 and 24 (Gordon, Langley, et al., 2006; Papp et al., 2005).
In a Phase 3 trial, 91% (274/301) of psoriasis patients receiving infliximab achieved PASI-50, and 80% (242/301) achieved PASI-75 at 10 weeks (Reich et al., 2005). However, the percentages of patients with PASI-50 and PASI-75 responses dropped to 69% and 61%, respectively, at Week 50. Again, although demonstrated efficacy rates were well above those in placebo-treated patients (8% [6/77] and 3% [2/77] of placebo-treated patients achieved PASI-50 and PASI-75, respectively, at 10 weeks), loss of response over time constitutes an inadequate response to treatment for many patients.
Inability to maintain or achieve PASI-50 has also been observed in 26% to 44% of patients receiving T-cell-modulating agents (Lebwohl, Christophers, et al., 2003; Lebwohl, Tyring, et al., 2003; Menter et al., 2005, 2006). A clinical trial assessing the efficacy of alefacept in psoriasis patients found that incremental efficacy was attained over multiple consecutive treatment courses: 56% of patients receiving alefacept achieved PASI-50 at 12 weeks, and a maximum of 74% of patients achieved PASI-50 at 60 weeks; over the same period, the PASI-75 rate increased from 29% to 54% (Menter et al., 2006). Although the observed increase in efficacy is significant, the fact remains that 26% of patients did not achieve PASI-50 after more than a year of continuous treatment. In clinical trials of psoriasis patients treated with efalizumab, 44% and 30% of patients did not achieve PASI-50 by Weeks 12 and 24, respectively (Lebwohl, Tyring, et al., 2003; Menter et al., 2005).
Patients who are dissatisfied with one psoriasis therapy may achieve better results by switching to a different treatment (Figures 1A and 1B). In addition, there are several situations in which healthcare providers might consider a change in treatment for their psoriasis patients. Among these are inadequate response to current therapy, onset of comorbidities that prompt health concerns with current treatment, and occurrence of adverse events. The benefit of switching from one class of biologic therapy to another has been described in case reports (Kramer, Turner, Kircik, Krusinski, & Snyder, 2006; Krell & Sobell, 2007; Turner, Baum, Bradley, & Eastern, 2008).
|FIGURE 1. Inadequate response to anti-TNF therapy (etanercept) (A) versus response after switching to anti-T-cell therapy (efalizumab) (B). Copyright by the |
REASONS TO CONSIDER SWITCHING THERAPIES
Various treatment options that employ different mechanisms of action are available. Inadequate disease response to one treatment does not preclude response to another therapy. However, it is important to give biologic therapies time to work before switching treatments. Biologic therapies commonly require weeks to produce a response, and it could take up to 12 weeks to see a significant change in symptoms. Health professionals should educate patients about the length of time it may take a biologic therapy to work so that patients do not become frustrated by a lack of immediate response to treatment.
Nevertheless, consideration should be given to switching treatment if moderate or severe psoriasis symptoms continue after 12 weeks of biologic therapy. Patients and care providers may also consider new treatment options if the patient's health status changes, if psoriasis continues to affect the patient's quality of life, or if clearing is not maintained over time.
Some comorbid conditions can affect the efficacy and safety of psoriasis therapy. For example, obesity, heart disease, psoriatic arthritis, or complicating infections may prompt a change in psoriasis therapy.
Obesity is being increasingly linked with psoriasis by common pathophysiological features (Sterry, Strober, & Menter, 2007). It is not well understood at this time whether or how increased body fat percentage in obese psoriasis patients affects the efficacy of biologic medications. However, there is evidence indicating that fixed-dose therapies are less effective in psoriasis patients who are overweight (Gordon, Korman, et al., 2006). In contrast, medications whose dosing regimen is based on individual patient weight do not seem to lose efficacy with increased weight (Clark & Lebwohl, 2008).
Psoriasis has also been linked to increased risk for myocardial infarction (Sterry et al., 2007). With respect to psoriasis treatment, TNF antagonists have been associated with cases of worsening congestive heart failure and new-onset congestive heart failure (Abbott, 2008; Behnam, Behnam, & Koo, 2005; Immunex Corporation, 2008; Kwon, Cote, Cuffe, Kramer, & Braun, 2003). In addition, the use of infliximab is contraindicated in patients with heart failure (Centocor, 2007). In general, the use of an alternative TNF antagonist in patients with heart failure should be considered cautiously, and such patients should be monitored carefully.
The emergence of psoriatic arthritis can have a large impact on determining which psoriasis treatment will produce the best results for a patient because biologics with differing mechanisms of action have varying efficacy against psoriatic arthritis. All three TNF antagonists are indicated for the treatment of joint symptoms in patients with psoriatic arthritis (Abbott Laboratories, 2008; Immunex Corporation, 2008; Centocor, 2007; Ravindran, Scott, & Choy, 2007). The T-cell modulator alefacept has also shown efficacy in this treatment context, although it is not currently indicated for the treatment of psoriatic arthritis (Astellas Pharma, 2006; Kraan et al., 2002; Mease, Gladman, Keystone, & Alefacept in Psoriatic Arthritis Study Group, 2006; Nash, 2006; Ravindran et al., 2007).
The presence of preexisting infections, which may be dormant, may complicate psoriasis treatment. Adalimumab, infliximab, and etanercept are associated with hepatitis B virus reactivation in patients who are chronic carriers of the virus, as well as with reactivation of latent tuberculosis infection (Abbott, 2008; Centocor, 2007; Immunex Corporation, 2008). Clinical experience indicates that infliximab has a higher rate of hepatitis B reactivation in particular compared with that of other TNF antagonists; there are some indications that pharmacological differences among anti-TNF agents may result in varying rates of hepatitis B viral reactivation (Carroll & Bond, 2008; Desai & Furst, 2006). However, medical professionals should exercise caution when using TNF antagonists to treat patients with chronic hepatitis B infection. Although data from clinical trials and preclinical studies suggest that the risk of reactivation of latent tuberculosis infection is lower with etanercept than that with other TNF antagonists, cases of tuberculosis reactivation have been reported for all anti-TNF agents, and the prescribing information for all three of these agents contains black box warnings regarding the reactivation of latent tuberculosis infection (Abbott, 2008; Centocor, 2007; Immunex Corporation, 2008). Proper screening and careful monitoring should be employed when treating psoriasis patients who have been exposed to hepatitis B or tuberculosis in the past, including patients who tested negative for latent tuberculosis infection.
Patients and medical professionals may also wish to consider switching therapies if the patient has an adverse reaction to a biologic psoriasis treatment. For example, efalizumab has been associated with the worsening of psoriasis symptoms or flares and the emergence of arthritic events (Genentech, Inc., 2005). Efalizumab use has also been associated with rare cases of immune-mediated thrombocytopenia and hemolytic anemia; it is recommended that patients who develop these conditions discontinue efalizumab therapy (Genentech, Inc., 2005). Infusion reactions may require switching from infliximab to a treatment option that is not delivered by intravenous injection (Centocor, 2007). On the other hand, injection site reactions, which can occur with the other TNF antagonists, can also become severe enough to require a change in treatment strategy (Brion, Mittal-Henkle, & Kalunian, 1999; McCain, Quinet, & Davis, 2002; Murphy, Enzenauer, Battafarano, & David-Bajar, 2000; Werth & Levinson, 2001). In addition, rare cases of new onset or exacerbation of central nervous system demyelinating disorders have been reported with TNF antagonists (Abbott Laboratories, 2008; Centocor, 2007; Immunex Corporation, 2008). Switching to a T-cell-modifying agent should be considered if such neurological symptoms become apparent.
IDENTIFYING AND MANAGING INADEQUATE RESPONSE
The dermatology nurse can be instrumental in evaluating the impact of psoriasis on a patient's quality of life and ensuring that patients receive adequate therapeutic intervention. It is also important for medical professionals to consider the patient's lifestyle and potential comorbidities when evaluating psoriasis and determining appropriate treatment. A checklist that incorporates some of the issues mentioned above has been developed to assist healthcare providers in assessing patient satisfaction with and clinical response to their current therapy (Figure 2). Key questions to ask include the following:
|FIGURE 2. Example of a patient satisfaction questionnaire.|
1. Does psoriasis continue to affect the patient's quality of life?
2. In what ways does psoriasis continue to adversely affect the patient?
3. How does the patient's current response to treatment compare with his or her best response?
4. Is the patient happy with his or her current regimen and response?
5. Has the patient's psoriasis condition worsened during treatment?
6. Has the patient developed any new health concerns or conditions?
Use of this checklist can help to define and communicate the patient's evaluation of current treatment and can highlight opportunities for healthcare professionals to educate patients about their treatment options. It can also aid in determining whether switching to a biologic treatment with a different mechanism of action is appropriate and can streamline treatment by reminding healthcare providers to carefully review patient response on a regular basis. Finally, by eliciting patient response, use of this checklist can help encourage patients to actively participate in their own healthcare and can encourage open communication between patients and their healthcare providers.
Surveys consistently show that many psoriasis patients are not receiving treatment or are not being treated according to current standards of care (Horn et al., 2007a; National Psoriasis Foundation, 2006). TNF antagonists and T-cell modulators provide a variety of treatment possibilities while employing two distinct mechanisms of action. This means that inadequate response to one therapy does not preclude successful response to another. Although biologic therapies require adequate time to demonstrate efficacy, medical professionals should consider exploring other treatment options if patients continue to have moderate or severe psoriasis symptoms after 12 weeks of therapy. Similarly, therapeutic complications or adverse effects in response to one treatment option do not necessarily preclude tolerance of another psoriasis therapy, and so comorbid conditions or adverse effects may also prompt a change in treatment regimen.
The dermatology nurse is in an excellent position to optimize disease management and patient response to psoriasis treatment. There are currently five biologic agents approved for the treatment of moderate to severe psoriasis. Healthcare professionals should be familiar with each of these agents to help educate patients regarding the wide array of available options. Use of a codified questionnaire can provide guidance to help healthcare professionals to "check in" with their patients regularly and can aid in the definition and evaluation of current treatment by patients. When dissatisfaction with or inadequate response to treatment is properly identified, medical professionals can work together with patients to decide whether switching to a new regimen is the best option.
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