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The Safety of Systemic Treatments That Can Be Used for Geriatric Psoriasis Patients: A Review

The Safety of Systemic Treatments That Can Be Used for Geriatric Psoriasis Patients: A Review Hindawi Publishing Corporation Dermatology Research and Practice Volume 2012, Article ID 367475, 4 pages doi:10.1155/2012/367475 Review Article The Safety of Systemic Treatments That Can Be Used for Geriatric Psoriasis Patients: A Review 1, 2 2 Jillian W. Wong and John Y. M. Koo University of Utah School of Medicine, Salt Lake City, UT 84132, USA Psoriasis and Skin Treatment Center, Department of Dermatology, University of California, San Francisco (UCSF), San Francisco, CA 94118, USA Correspondence should be addressed to Jillian W. Wong, jillianwwong@gmail.com Received 29 December 2011; Revised 14 March 2012; Accepted 30 March 2012 Academic Editor: Giuseppe Stinco Copyright © 2012 J. W. Wong and J. Y. M. Koo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Patients with moderate-to-severe psoriasis are often treated with systemic immunosuppressant agents that decrease immune system function. For the elderly, these medications are often problematic due to their already immunosuppressed state and comorbidities. However, there are few studies examining the effects of these medications on the elderly age group. Therefore, there is often discomfort among dermatologists treating elderly patients with psoriasis in utilizing systemic agents, frequently resulting in inadequate treatment. Objective. We review the safety profiles of systemic treatments often used to treat psoriasis and their possible adverse risks to the geriatric population. Methods. We conducted a search of PubMed’s Medline database of articles published from 2000 to 2011, which resulted in 14 articles. Conclusion. Treating geriatric patients with moderate-to-severe psoriasis remains a challenge due to immunosenescence and comorbidities. More studies focusing on psoriasis treatment safety in the geriatric population are needed. 1. Introduction elderly are at a higher risk than younger age groups to develop cancer, infectious disease, neurodegenerative dis- Psoriasis is a chronic, debilitating skin disease that affects ap- ease, and chronic inflammatory diseases such as atheroscle- proximately 2.6% of the general population [1]. Patients with rosis. However, immunosuppressive therapies are consid- psoriasis develop erythematous, scaly, and well-demarcated ered the mainstay for managing psoriasis and make up plaques that are often pruritic and can be painful. Due to the majority of systemic psoriasis treatments. The second its chronic nature, psoriasis increasingly affects the geriatric key problem in treating geriatric patients with psoriasis is population. A US study in 1991 reported that the highest rate that the elderly often have comorbid illnesses that can be of psoriasis, 113/100,000 population, occurred in the 60- to worsened by adverse effects of psoriasis therapies. Older 69-year age group [2]. With the growing geriatric population patients frequently have one or more comorbid illnesses that expected to compose 25% of the US population by 2020, the include cardiovascular disease, kidney insufficiency, liver dis- prevalence of psoriasis is also expected to rise [3]. ease, dementia and cognitive disability, diabetes, metabolic There are two key challenges for treating an older patient syndrome, and obesity, to name a few. with psoriasis. The first key challenge involves the already There are few studies examining the effects of these sys- immunosuppressed state of the elderly, also known as im- temic medications on the elderly age group. Therefore, there munosenescence. Immunosenescence is a term that describes is often discomfort among dermatologists treating elderly the immunosuppressed state of the elderly due to natural patients with psoriasis. Herein, we review the safety profile aging [4]. This is due to a marked decrease in T-cell func- tion with aging as well as other age-related changes in of systemic agents often prescribed for psoriasis and their innate immunity [5]. As a result of immunosenescence, the possible adverse effects on the geriatric population. 2 Dermatology Research and Practice 2. Methods 3,598 nonbiologic treated patients from the British Society for Rheumatology Biologics Registry [12]. The consequence We conducted a search of PubMed’s Medline database of for this study is that physicians are less likely to prescribe bio- articles published from 2000 to 2011 to include only the most logic agents to the elderly because of their already decreased recent literature. Articles containing the key words geriatric immune function. However, one study demonstrated long- population, elderly, immunosuppression, and psoriasis were term safety of etanercept on elderly patients with rheumatic reviewed. In addition, different treatment modalities includ- diseases. The study measured serious adverse events, infec- ing biologic agents, acitretin, cyclosporine, and methotrexate tious events, medically important infections, and deaths were combined with the key words geriatric and elderly.The in 597 geriatric patients over the age of 65 and 3,296 search was limited to articles in English. The search initially nongeriatric patients with rheumatic diseases [13]. It found resulted in 338 articles. Article abstracts were reviewed for no statistically significant difference in safety between elderly relevance to the subject matter. We examined reference and younger age groups [13]. lists to identify any missing articles. Articles included in A study by Militello et al. compared the efficacy and the review specifically discussed the use of systemic agents tolerability of etanercept for the treatment of psoriasis in in the elderly, the safety profiles of the systemic agents, elderly and nonelderly populations. The study found that and/or adverse risks to the elderly. Articles excluded from the there were no significant differences in the quality of life, as review included studies and other review articles that did not measured by the Dermatology Life Quality Index (DLQI), specifically discuss the use of systemic agents in the elderly and in efficacy, as measured by Psoriasis Area and Severity population or the safety profiles of systemic agents. Index (PASI) [14]. Although it showed that there was a significant increase in serious adverse events in the elderly 3. Results group, these events were reported as not associated with treatment with etanercept. In addition, injection site reaction After a thorough assessment of articles in the Medline data- events were not significantly different between the older and base, 14 relevant articles were included in this review. 4 Food younger age groups [14]. and Drug Administration (FDA) package labels were also Furthermore, FDA labeling for biologic agents raises con- incorporated in the review. cerns for safety in the elderly. According to the FDA package Systemic immunosuppressive therapies for psoriasis in- insert for adalimumab (Humira), the frequency of serious clude biologic agents such as adalimumab, infliximab, etan- infections and malignancies was higher in the elderly than ercept (tumor necrosis factor (TNF) α blockers), ustekin- in younger cohorts [15]. The package inserts for infliximab umab (interleukin 12/23 monoclonal antibody), and alefa- (Remicade), ustekinumab (Stelara), and etanercept (Enbrel), cept (T-cell inhibitor). In the treatment of psoriasis, there are however, reported no overall difference in safety in the also options of nonbiologic immunosuppressive agents that geriatric population compared to younger age groups [16– include cyclosporine and methotrexate and a nonimmuno- 18]. The package inserts for infliximab, ustekinumab, and suppressive systemic agent, acitretin. etanercept also warn that because the risk of infection is higher in the elderly in general, caution should be used when 3.1. Systemic Agents and Immunosuppression. Immunosup- administering these medications in the geriatric population. pression is a concern when using biologic agents. Adali- mumab and infliximab have been demonstrated to increase 3.2. Systemic Agents and Comorbidities. One biologic agent, tuberculosis risk [6], histoplasmosis [7], and other granulo- ustekinumab, has been implicated in possible increased risk matous diseases [8]aswellasherpeszoster[9]and malig- to cardiovascular health. The immunosuppressive agent, nancy [10]. Ustekinumab has been implicated to increase cyclosporine has not been studied in elderly with psoriasis cardiovascular risk due to earlier phase II research findings, specifically but has the potential to cause damage to sev- although later data did not demonstrate such risks. In phase eral organ systems. Elderly patients often have decreased II trials of ustekinumab, more adverse cardiovascular events baseline renal impairment due to aging. Cyclosporine can (MACE) such as heart attack, stroke, and sudden cardiac worsen renal insufficiency and can raise the creatinine death were found in the experimental group than the placebo level. Age-related decline in renal clearance of cyclosporine group in psoriasis trials [11]. However, this has not been has been shown in geriatric kidney transplant recipients shown in phase III trials or four-year long-term data. [19]. Cyclosporine also can increase blood pressure, which There have been some studies that compare the use is carefully monitored for the side effect of hypertension at of immunosuppressive agents between older and younger each clinic visit. Cyclosporine cannot be used in patients cohorts with rheumatologic diseases, such as rheumatoid with abnormal baseline serum creatinine and glomerular arthritis, psoriatic arthritis, and ankylosing spondylitis. Safe- filtration rate and is used with caution in the elderly [20]. ty data extrapolated from the literature of rheumatologic diseases raises concern for using these agents in the elderly. Methotrexate is another effective nonbiologic immuno- A study of all anti-TNF α agents in patients with rheumatoid suppressive psoriasis treatment that can adversely affect arthritis showed that there was a significant overall risk of multiple organ systems. A major concern for possible harm increased serious infections of the elderly over age 65 com- of methotrexate is to the hepatic system, as methotrexate pared to younger cohorts [12]. The study compared the risk has been implicated in hepatic fibrosis and cirrhosis. Elderly of serious infections in 11,798 anti-TNF treated patients and patients are at increased risk for hepatotoxicity because of Dermatology Research and Practice 3 an increased tendency for elevated triglycerides, elevated liver allergies and side effects of medications to prevent adverse function tests, and obesity that are often found in the aging drug interactions and reactions. A careful history of immu- population and are associated with methotrexate-related nosuppressive use is needed to ensure that the cumulative hepatic fibrosis [20]. A liver biopsy is required with long- dose of the agent is not beyond the standard recommended term use of methotrexate, a risk for the elderly that may out- by the FDA to cause toxicity to an organ system. The physical weigh the benefits of preventing liver damage. Methotrexate examination should be a thorough head-to-toe examination, renal clearance is inversely proportional to the patient’s age with particular emphasis on the cardiovascular, respiratory, and, therefore, increases renal insufficiency in the elderly, and musculoskeletal systems. Vital signs should be taken making this agent more problematic [21]. Myelosuppression twice, in particular to ensure that the patient does not is another rare side effect occurring in the geriatric pop- have hypertension if the physician is planning to prescribe ulation associated with this medication [22]. Patients on cyclosporine. Extensive laboratory workup is needed to methotrexate with comorbid diabetes mellitus are at greater evaluate for hepatic decline (liver function tests), renal risk for cirrhosis and severe liver fibrosis [23]. insufficiency (creatinine and possibly glomerular filtration rate), hyperlipidemia, electrolytes, low white blood cell One systemic agent for psoriasis that is not an immuno- count, low platelets, and low red blood cell count that suppressant is acitretin. It is also an effective psoriasis treat- would be considered contraindications for certain systemic ment. Though not an immunosuppressant, it also has the therapies. potential to cause harm to several organ systems, raising con- cern for use in the elderly. Acitretin is a second-generation When prescribing medications, it is important to start retinoid that may increase cardiovascular risk. It can cause with a small dose and then titrate up to higher doses to hypertriglyceridemia [20, 23]. In addition, it adversely affects a defined therapeutic response. Physicians should make an the integumentary system by increasing dryness of the skin effort to reduce the number of medications the patient needs and mucosal membranes. This exacerbates xerosis that is to take and should regularly check for possible interactions alreadymorecommoninthisage group. and adverse effects. Another issue that arises when treating the geriatric For a healthy, active elderly patient with no or limited population is polypharmacy and consequent drug interac- comorbidities, etanercept can be used for psoriasis treatment tions. Old age is associated with decreased excretory kidney with careful monitoring. Etanercept has been the only sys- capacity, causing higher risk for adverse drug reactions and temic biologic agent that has shown to be safe in the interactions especially with multidrug regimens commonly elderly, possibly due to its lower immunosuppressive ability seen in this population. Methotrexate, for example, has compared to other biologic agents. However, a larger sample a potentially fatal drug interaction with trimethoprim, a size of psoriasis-specific elderly patients is needed to further common mainstream antibiotic [20]. confirm its safety. If an elderly patient has multiple comorbidities and risk factors that make him/her a poor candidate for an oral 4. Discussion or injectable systemic agent, phototherapy and strict com- pliance to topical therapies are recommended. Ultraviolet Based on studies and known risks of systemic medications, B (UVB) and psoralen ultraviolet A (PUVA) phototherapy physicians and patients both face challenges for determining are noninvasive with minimal side effects limited to mild how to adequately treat psoriasis and avoiding increased erythema, burning, and blistering. However, the patient may harm that may outweigh the benefits of treatment. Further be challenged by the phototherapy box that requires him or research is needed to develop and make possible medications her to be able to stand in the unit without mobile support with decreased risk for cancer, infection, and worsening or guard rails to maintain balance. In addition, some geri- comorbidities. Extensive studies should be carried out to atric patients lack transportation or have arthritis or hip understand the effects of these systemic agents specifically impairment that prevent them from being able to move on the geriatric psoriasis population. In addition to research, themselves to a dermatology clinic for phototherapy. Drug- the management of elderly patients with psoriasis can be induced photosensitivity can also occur if a careful drug improved by educational programs. Currently, many der- history is not taken. matologists are not comfortable with treating the elderly psoriasis patient with these agents and are inadequately treating them by using topical therapies alone. However, a 5. Conclusion consensus meeting of geriatric dermatology experts should be organized to develop specific guidelines for dermatol- There is heightened concern about the use of systemic pso- ogists and other physicians about optional treatments for riasis medications for the elderly. These medications can be psoriasis in the elderly. very effective and are considered the mainstay of treatment For now, however, without specific guidelines and ade- for moderate-to-sever psoriasis. Virtually all new agents quate research into this topic, a more careful management being developed to treat psoriasis are immunosuppressants. of the elderly patient with psoriasis is needed. A cautious However, studies have demonstrated increased risk involved approach can be taken with a thorough history and physical in treating elderly patients with these therapies due to examination. Included in the history, physicians should increased comorbidities and immunosenescence. Therefore, document all current and past medications as well as drug many elderly patients are not adequately treated and suffer 4 Dermatology Research and Practice the physical and psychological effects of psoriasis. These [11] K. Reich, R. G. Langley, M. Lebwohl et al., “Cardiovascular safety of ustekinumab in patients with moderate to severe pso- include discomfort and pain from psoriatic plaques as well as riasis: results of integrated analyses of data from phase II and depression, anxiety, and stigma from the public because the III clinical studies,” British Journal of Dermatology, vol. 164, plaques are often disfiguring. Physicians should remember no. 4, pp. 862–872, 2011. that the goals of treating psoriasis in the elderly are to achieve [12] J. B. Galloway, K. L. Hyrich, L. K. Mercer et al., “Anti-TNF clinical control of the skin disease, improve quality of life of therapy is associated with an increased risk of serious infec- the patient, and administer safe and tolerable treatments. It tions in patients with rheumatoid arthritis especially in the is important for physicians and health care workers serving first 6 months of treatment: updated results from the British this patient population to understand the risks associated Society for Rheumatology Biologics Register with special em- with systemic agents, initiate and engage in research focusing phasis on risks in the elderly,” Rheumatology,vol. 50, no.1,pp. on the elderly to study these agents and also to investigate 124–131, 2011. new psoriasis therapies, and be willing to treat these patients [13] R. Fleischmann, S. W. Baumgartner, M. H. Weisman, T. Liu, B. White, and P. Peloso, “Long term safety of etanercept in elderly thoroughly and cautiously so that they are able to obtain subjects with rheumatic diseases,” Annals of the Rheumatic adequate treatment to decrease suffering of generalized Diseases, vol. 65, no. 3, pp. 379–384, 2006. psoriasis. [14] G. Militello, A. Xia, S. R. Stevens, and A. S. Van Voorhees, “Etanercept for the treatment of psoriasis in the elderly,” Conflict of Interests Journal of the American Academy of Dermatology, vol. 55, no. 3, pp. 517–519, 2006. J. W. Wong has no financial conflict of interests to disclose. [15] Adalimumab [package insert], North Chicago, Ill, USA, 2002, J. Y. M. Koo has the following conflict of interests: Abbott, http://www.accessdata.fda.gov/drugsatfda docs/label/2002/ Amgen, Leo, Galderma, GlaxoSmithKlein, Novartis, Pho- adalabb123102LB.htm. toMedex, Pfizer, and Teikoku. [16] Infliximab [package insert], Janssen, Toronto, Ontario, Ca- nada, 2010, http://www.remicade.com/remicade/assets/HCP PPI.pdf. References [17] Ustekinumab [package insert], Janssen Biotech, Horsham, Pa, USA, 2011, http://www.drugs.com/pro/stelara.html. [1] J. Koo, “Population-based epidemiologic study of psoriasis [18] Etanercept [package insert], Amgen,Thousand Oaks, Calif, with emphasis on quality of life assessment,” Dermatologic USA, 1998–2011, http://pi.amgen.com/united states/enbrel/ Clinics, vol. 14, no. 3, pp. 485–496, 1996. derm/enbrel pi.pdf. [2] L. M. Bell, R. Sedlack, C. M. Beard, H. O. Perry, C. J. Michet, [19] P. Falck, A. Asberg, K. T. Byberg et al., “Reduced elimination and L. T. Kurland, “Incidence of psoriasis in Rochester, Minn, of cyclosporine a in elderly (>65 Years) kidney transplant 1980–1983,” Archives of Dermatology, vol. 127, no. 8, pp. 1184– recipients,” Transplantation, vol. 86, no. 10, pp. 1379–1383, 1187, 1991. [3] R. A. Norman, Diagnosis of Aging Skin Disease, Springer, [20] I. S. Grozdev, A. S. Van Voorhees, A. B. Gottlieb et al., “Pso- London, UK, 2008. riasis in the elderly: from the Medical Board of the National ¨ ¨ [4] T. Fulop, A. Larbi, K. Hirokawa et al., “Immunosupportive Psoriasis Foundation,” Journal of the American Academy of therapies in aging,” Clinical Interventions in Aging, vol. 2, no. Dermatology, vol. 65, pp. 537–545, 2011. 1, pp. 33–54, 2007. [21] G. M. Fairris, A. G. Dewhurst, J. E. White, and M. J. Campbell, “Methotrexate dosage in patients aged over 50 with psoriasis,” [5] S. Vasto, M. Malavolta, and G. Pawelec, “Age and immunity,” British Medical Journal, vol. 298, no. 6676, pp. 801–802, 1989. Immunity and Ageing, vol. 3, article 2, 2006. [22] M. J. Boffa and R. J. G. Chalmers, “Methotrexate for psoriasis,” [6] I.Solovic, M. Sester,J.J.Gomez-Reino et al., “The risk of Clinical and Experimental Dermatology, vol. 21, no. 6, pp. 399– tuberculosis related to tumour necrosis factor antagonist ther- 408, 1996. apies: a TBNET consensus statement,” European Respiratory [23] S. Hsu, K. A. Papp, M. G. Lebwohl et al., “Consensus guide- Journal, vol. 36, no. 5, pp. 1185–1206, 2010. lines for the management of plaque psoriasis,” Archives of [7] C.A.Hage, S. Bowyer,S.E.Tarvin, D. Helper,M.B.Kleiman, Dermatology, vol. 148, pp. 95–102, 2012. and L. J. Wheat, “Recognition, diagnosis, and treatment of histoplasmosis complicating tumor necrosis factor blocker therapy,” Clinical Infectious Diseases, vol. 50, no. 1, pp. 85–92, [8] R. S. Wallis, “Biologics and infections: lessons from tumor necrosis factor blocking agents,” Infectious Disease Clinics of North America, vol. 25, pp. 895–910, 2011. [9] M. J. Perez-Sola, J. Torre-Cisneros, B. Perez-Zafrilla, L. Carmona, M. A. Descalzo, and J. J. Gomez-Reino, “Infections in patients treated with tumor necrosis factor antagonists: incidence, etiology and mortality in the BIOBADASER reg- istry,” Medicina Cl´ınica, vol. 137, no. 12, pp. 533–540, 2011. [10] S. K. Okada and J. N. Siegel, “Risk of serious infections and malignancies with anti-TNF antibody therapy in rheumatoid arthritis,” Journal of the American Medical Association, vol. 296, no. 18, pp. 2201–2202, 2006. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Dermatology Research and Practice Pubmed Central

The Safety of Systemic Treatments That Can Be Used for Geriatric Psoriasis Patients: A Review

Dermatology Research and Practice , Volume 2012 – May 28, 2012

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Copyright © 2012 J. W. Wong and J. Y. M. Koo.
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Abstract

Hindawi Publishing Corporation Dermatology Research and Practice Volume 2012, Article ID 367475, 4 pages doi:10.1155/2012/367475 Review Article The Safety of Systemic Treatments That Can Be Used for Geriatric Psoriasis Patients: A Review 1, 2 2 Jillian W. Wong and John Y. M. Koo University of Utah School of Medicine, Salt Lake City, UT 84132, USA Psoriasis and Skin Treatment Center, Department of Dermatology, University of California, San Francisco (UCSF), San Francisco, CA 94118, USA Correspondence should be addressed to Jillian W. Wong, jillianwwong@gmail.com Received 29 December 2011; Revised 14 March 2012; Accepted 30 March 2012 Academic Editor: Giuseppe Stinco Copyright © 2012 J. W. Wong and J. Y. M. Koo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Patients with moderate-to-severe psoriasis are often treated with systemic immunosuppressant agents that decrease immune system function. For the elderly, these medications are often problematic due to their already immunosuppressed state and comorbidities. However, there are few studies examining the effects of these medications on the elderly age group. Therefore, there is often discomfort among dermatologists treating elderly patients with psoriasis in utilizing systemic agents, frequently resulting in inadequate treatment. Objective. We review the safety profiles of systemic treatments often used to treat psoriasis and their possible adverse risks to the geriatric population. Methods. We conducted a search of PubMed’s Medline database of articles published from 2000 to 2011, which resulted in 14 articles. Conclusion. Treating geriatric patients with moderate-to-severe psoriasis remains a challenge due to immunosenescence and comorbidities. More studies focusing on psoriasis treatment safety in the geriatric population are needed. 1. Introduction elderly are at a higher risk than younger age groups to develop cancer, infectious disease, neurodegenerative dis- Psoriasis is a chronic, debilitating skin disease that affects ap- ease, and chronic inflammatory diseases such as atheroscle- proximately 2.6% of the general population [1]. Patients with rosis. However, immunosuppressive therapies are consid- psoriasis develop erythematous, scaly, and well-demarcated ered the mainstay for managing psoriasis and make up plaques that are often pruritic and can be painful. Due to the majority of systemic psoriasis treatments. The second its chronic nature, psoriasis increasingly affects the geriatric key problem in treating geriatric patients with psoriasis is population. A US study in 1991 reported that the highest rate that the elderly often have comorbid illnesses that can be of psoriasis, 113/100,000 population, occurred in the 60- to worsened by adverse effects of psoriasis therapies. Older 69-year age group [2]. With the growing geriatric population patients frequently have one or more comorbid illnesses that expected to compose 25% of the US population by 2020, the include cardiovascular disease, kidney insufficiency, liver dis- prevalence of psoriasis is also expected to rise [3]. ease, dementia and cognitive disability, diabetes, metabolic There are two key challenges for treating an older patient syndrome, and obesity, to name a few. with psoriasis. The first key challenge involves the already There are few studies examining the effects of these sys- immunosuppressed state of the elderly, also known as im- temic medications on the elderly age group. Therefore, there munosenescence. Immunosenescence is a term that describes is often discomfort among dermatologists treating elderly the immunosuppressed state of the elderly due to natural patients with psoriasis. Herein, we review the safety profile aging [4]. This is due to a marked decrease in T-cell func- tion with aging as well as other age-related changes in of systemic agents often prescribed for psoriasis and their innate immunity [5]. As a result of immunosenescence, the possible adverse effects on the geriatric population. 2 Dermatology Research and Practice 2. Methods 3,598 nonbiologic treated patients from the British Society for Rheumatology Biologics Registry [12]. The consequence We conducted a search of PubMed’s Medline database of for this study is that physicians are less likely to prescribe bio- articles published from 2000 to 2011 to include only the most logic agents to the elderly because of their already decreased recent literature. Articles containing the key words geriatric immune function. However, one study demonstrated long- population, elderly, immunosuppression, and psoriasis were term safety of etanercept on elderly patients with rheumatic reviewed. In addition, different treatment modalities includ- diseases. The study measured serious adverse events, infec- ing biologic agents, acitretin, cyclosporine, and methotrexate tious events, medically important infections, and deaths were combined with the key words geriatric and elderly.The in 597 geriatric patients over the age of 65 and 3,296 search was limited to articles in English. The search initially nongeriatric patients with rheumatic diseases [13]. It found resulted in 338 articles. Article abstracts were reviewed for no statistically significant difference in safety between elderly relevance to the subject matter. We examined reference and younger age groups [13]. lists to identify any missing articles. Articles included in A study by Militello et al. compared the efficacy and the review specifically discussed the use of systemic agents tolerability of etanercept for the treatment of psoriasis in in the elderly, the safety profiles of the systemic agents, elderly and nonelderly populations. The study found that and/or adverse risks to the elderly. Articles excluded from the there were no significant differences in the quality of life, as review included studies and other review articles that did not measured by the Dermatology Life Quality Index (DLQI), specifically discuss the use of systemic agents in the elderly and in efficacy, as measured by Psoriasis Area and Severity population or the safety profiles of systemic agents. Index (PASI) [14]. Although it showed that there was a significant increase in serious adverse events in the elderly 3. Results group, these events were reported as not associated with treatment with etanercept. In addition, injection site reaction After a thorough assessment of articles in the Medline data- events were not significantly different between the older and base, 14 relevant articles were included in this review. 4 Food younger age groups [14]. and Drug Administration (FDA) package labels were also Furthermore, FDA labeling for biologic agents raises con- incorporated in the review. cerns for safety in the elderly. According to the FDA package Systemic immunosuppressive therapies for psoriasis in- insert for adalimumab (Humira), the frequency of serious clude biologic agents such as adalimumab, infliximab, etan- infections and malignancies was higher in the elderly than ercept (tumor necrosis factor (TNF) α blockers), ustekin- in younger cohorts [15]. The package inserts for infliximab umab (interleukin 12/23 monoclonal antibody), and alefa- (Remicade), ustekinumab (Stelara), and etanercept (Enbrel), cept (T-cell inhibitor). In the treatment of psoriasis, there are however, reported no overall difference in safety in the also options of nonbiologic immunosuppressive agents that geriatric population compared to younger age groups [16– include cyclosporine and methotrexate and a nonimmuno- 18]. The package inserts for infliximab, ustekinumab, and suppressive systemic agent, acitretin. etanercept also warn that because the risk of infection is higher in the elderly in general, caution should be used when 3.1. Systemic Agents and Immunosuppression. Immunosup- administering these medications in the geriatric population. pression is a concern when using biologic agents. Adali- mumab and infliximab have been demonstrated to increase 3.2. Systemic Agents and Comorbidities. One biologic agent, tuberculosis risk [6], histoplasmosis [7], and other granulo- ustekinumab, has been implicated in possible increased risk matous diseases [8]aswellasherpeszoster[9]and malig- to cardiovascular health. The immunosuppressive agent, nancy [10]. Ustekinumab has been implicated to increase cyclosporine has not been studied in elderly with psoriasis cardiovascular risk due to earlier phase II research findings, specifically but has the potential to cause damage to sev- although later data did not demonstrate such risks. In phase eral organ systems. Elderly patients often have decreased II trials of ustekinumab, more adverse cardiovascular events baseline renal impairment due to aging. Cyclosporine can (MACE) such as heart attack, stroke, and sudden cardiac worsen renal insufficiency and can raise the creatinine death were found in the experimental group than the placebo level. Age-related decline in renal clearance of cyclosporine group in psoriasis trials [11]. However, this has not been has been shown in geriatric kidney transplant recipients shown in phase III trials or four-year long-term data. [19]. Cyclosporine also can increase blood pressure, which There have been some studies that compare the use is carefully monitored for the side effect of hypertension at of immunosuppressive agents between older and younger each clinic visit. Cyclosporine cannot be used in patients cohorts with rheumatologic diseases, such as rheumatoid with abnormal baseline serum creatinine and glomerular arthritis, psoriatic arthritis, and ankylosing spondylitis. Safe- filtration rate and is used with caution in the elderly [20]. ty data extrapolated from the literature of rheumatologic diseases raises concern for using these agents in the elderly. Methotrexate is another effective nonbiologic immuno- A study of all anti-TNF α agents in patients with rheumatoid suppressive psoriasis treatment that can adversely affect arthritis showed that there was a significant overall risk of multiple organ systems. A major concern for possible harm increased serious infections of the elderly over age 65 com- of methotrexate is to the hepatic system, as methotrexate pared to younger cohorts [12]. The study compared the risk has been implicated in hepatic fibrosis and cirrhosis. Elderly of serious infections in 11,798 anti-TNF treated patients and patients are at increased risk for hepatotoxicity because of Dermatology Research and Practice 3 an increased tendency for elevated triglycerides, elevated liver allergies and side effects of medications to prevent adverse function tests, and obesity that are often found in the aging drug interactions and reactions. A careful history of immu- population and are associated with methotrexate-related nosuppressive use is needed to ensure that the cumulative hepatic fibrosis [20]. A liver biopsy is required with long- dose of the agent is not beyond the standard recommended term use of methotrexate, a risk for the elderly that may out- by the FDA to cause toxicity to an organ system. The physical weigh the benefits of preventing liver damage. Methotrexate examination should be a thorough head-to-toe examination, renal clearance is inversely proportional to the patient’s age with particular emphasis on the cardiovascular, respiratory, and, therefore, increases renal insufficiency in the elderly, and musculoskeletal systems. Vital signs should be taken making this agent more problematic [21]. Myelosuppression twice, in particular to ensure that the patient does not is another rare side effect occurring in the geriatric pop- have hypertension if the physician is planning to prescribe ulation associated with this medication [22]. Patients on cyclosporine. Extensive laboratory workup is needed to methotrexate with comorbid diabetes mellitus are at greater evaluate for hepatic decline (liver function tests), renal risk for cirrhosis and severe liver fibrosis [23]. insufficiency (creatinine and possibly glomerular filtration rate), hyperlipidemia, electrolytes, low white blood cell One systemic agent for psoriasis that is not an immuno- count, low platelets, and low red blood cell count that suppressant is acitretin. It is also an effective psoriasis treat- would be considered contraindications for certain systemic ment. Though not an immunosuppressant, it also has the therapies. potential to cause harm to several organ systems, raising con- cern for use in the elderly. Acitretin is a second-generation When prescribing medications, it is important to start retinoid that may increase cardiovascular risk. It can cause with a small dose and then titrate up to higher doses to hypertriglyceridemia [20, 23]. In addition, it adversely affects a defined therapeutic response. Physicians should make an the integumentary system by increasing dryness of the skin effort to reduce the number of medications the patient needs and mucosal membranes. This exacerbates xerosis that is to take and should regularly check for possible interactions alreadymorecommoninthisage group. and adverse effects. Another issue that arises when treating the geriatric For a healthy, active elderly patient with no or limited population is polypharmacy and consequent drug interac- comorbidities, etanercept can be used for psoriasis treatment tions. Old age is associated with decreased excretory kidney with careful monitoring. Etanercept has been the only sys- capacity, causing higher risk for adverse drug reactions and temic biologic agent that has shown to be safe in the interactions especially with multidrug regimens commonly elderly, possibly due to its lower immunosuppressive ability seen in this population. Methotrexate, for example, has compared to other biologic agents. However, a larger sample a potentially fatal drug interaction with trimethoprim, a size of psoriasis-specific elderly patients is needed to further common mainstream antibiotic [20]. confirm its safety. If an elderly patient has multiple comorbidities and risk factors that make him/her a poor candidate for an oral 4. Discussion or injectable systemic agent, phototherapy and strict com- pliance to topical therapies are recommended. Ultraviolet Based on studies and known risks of systemic medications, B (UVB) and psoralen ultraviolet A (PUVA) phototherapy physicians and patients both face challenges for determining are noninvasive with minimal side effects limited to mild how to adequately treat psoriasis and avoiding increased erythema, burning, and blistering. However, the patient may harm that may outweigh the benefits of treatment. Further be challenged by the phototherapy box that requires him or research is needed to develop and make possible medications her to be able to stand in the unit without mobile support with decreased risk for cancer, infection, and worsening or guard rails to maintain balance. In addition, some geri- comorbidities. Extensive studies should be carried out to atric patients lack transportation or have arthritis or hip understand the effects of these systemic agents specifically impairment that prevent them from being able to move on the geriatric psoriasis population. In addition to research, themselves to a dermatology clinic for phototherapy. Drug- the management of elderly patients with psoriasis can be induced photosensitivity can also occur if a careful drug improved by educational programs. Currently, many der- history is not taken. matologists are not comfortable with treating the elderly psoriasis patient with these agents and are inadequately treating them by using topical therapies alone. However, a 5. Conclusion consensus meeting of geriatric dermatology experts should be organized to develop specific guidelines for dermatol- There is heightened concern about the use of systemic pso- ogists and other physicians about optional treatments for riasis medications for the elderly. These medications can be psoriasis in the elderly. very effective and are considered the mainstay of treatment For now, however, without specific guidelines and ade- for moderate-to-sever psoriasis. Virtually all new agents quate research into this topic, a more careful management being developed to treat psoriasis are immunosuppressants. of the elderly patient with psoriasis is needed. A cautious However, studies have demonstrated increased risk involved approach can be taken with a thorough history and physical in treating elderly patients with these therapies due to examination. Included in the history, physicians should increased comorbidities and immunosenescence. Therefore, document all current and past medications as well as drug many elderly patients are not adequately treated and suffer 4 Dermatology Research and Practice the physical and psychological effects of psoriasis. These [11] K. Reich, R. G. Langley, M. Lebwohl et al., “Cardiovascular safety of ustekinumab in patients with moderate to severe pso- include discomfort and pain from psoriatic plaques as well as riasis: results of integrated analyses of data from phase II and depression, anxiety, and stigma from the public because the III clinical studies,” British Journal of Dermatology, vol. 164, plaques are often disfiguring. 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Published: May 28, 2012

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