Comparative effectiveness of less commonly used systemic monotherapies and common combination therapies for moderate to severe psoriasis in the clinical setting

doi:10.1016/j.jaad.2014.08.003

Journal of the American Academy of Dermatology

Volume 71, Issue 6, December 2014, Pages 1167-1175

An abstract of the data contained in this article was presented at the International Investigative Dermatology Meeting in Edinburgh, Scotland, May 8-11, 2013.

https://doi.org/10.1016/j.jaad.2014.08.003 Get rights and content

Background

The effectiveness of psoriasis therapies in real-world settings remains relatively unknown.

Objective

We sought to compare the effectiveness of less commonly used systemic therapies and commonly used combination therapies for psoriasis.

Methods

This was a multicenter cross-sectional study of 203 patients with plaque psoriasis receiving less common systemic monotherapy (acitretin, cyclosporine, or infliximab) or common combination therapies (adalimumab, etanercept, or infliximab and methotrexate) compared with 168 patients receiving methotrexate evaluated at 1 of 10 US outpatient dermatology sites participating in the Dermatology Clinical Effectiveness Research Network.

Results

In adjusted analyses, patients on acitretin (relative response rate 2.01; 95% confidence interval [CI] 1.18-3.41), infliximab (relative response rate 1.93; 95% CI 1.26-2.98), adalimumab and methotrexate (relative response rate 3.04; 95% CI 2.12-4.36), etanercept and methotrexate (relative response rate 2.22; 95% CI 1.25-3.94), and infliximab and methotrexate (relative response rate 1.72; 95% CI 1.10-2.70) were more likely to have clear or almost clear skin compared with patients on methotrexate. There were no differences among treatments when response rate was defined by health-related quality of life.

Limitations

Single time point assessment may result in overestimation of effectiveness.

Conclusions

The efficacy of therapies in clinical trials may overestimate their effectiveness as used in clinical practice. Although physician-reported relative response rates were different among therapies, absolute differences were small and did not correspond to differences in patient-reported outcomes.

Section snippets

Study design and participant protection

We conducted a multicenter cross-sectional study to determine the effectiveness of less commonly used systemic monotherapy and commonly used combination therapies for moderate to severe psoriasis. The study was approved by the University of Pennsylvania and University of Utah institutional review boards, and informed consent was obtained from all patients. The study was conducted in accordance with the Declaration of Helsinki and reported in accordance with the Strengthening the Reporting of

Results

The baseline characteristics of 371 patients receiving methotrexate (reference therapy), less common systemic monotherapies, or common combination therapies for the primary indication of plaque psoriasis are summarized in Table I. In addition to having plaque psoriasis, 75 (20.2%) patients also had other types of psoriasis as follows: 38 (10.2%) with scalp, 20 (5.4%) with guttate, 22 (5.9%) with nail, 16 (4.3%) with inverse or genital, 11 (3.0%) with palmar plantar, and 2 (0.5%) with pustular

Discussion

In this comparative effectiveness study of less commonly used systemic monotherapies and common combination therapies for moderate to severe psoriasis in the real-world clinical setting, we report similar findings to those of our previous study of the effectiveness of common systemic monotherapies and phototherapy.⁵ Using a single PGA assessment, the proportions of patients achieving clear or almost clear response to treatment were 50% or less for all examined therapies except for adalimumab

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Cited by (23)

Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies
2020, Journal of the American Academy of Dermatology
Citation Excerpt :
Cyclosporine should be avoided in patients with poor health and in those with risk factors for developing severe adverse effects.112 Recommendations for the use of cyclosporine are outlined in Table X, and the level of evidence of these recommendations is reported in Table XI.33,50,105,112,146-149 The oral retinoid, acitretin, is a vitamin A derivative, and the active metabolite, etretinate, is an oral retinoid that was initially used for psoriasis in the early 1980s.
Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).
Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics
2019, Journal of the American Academy of Dermatology
Citation Excerpt :
This combination is well established in the treatment of both rheumatoid arthritis and PsA. Likewise, there are substantial and convincing data documenting the safety and efficacy of this combination for patients with psoriasis.60-62 There are limited data from a retrospective case series indicating that apremilast could be combined with etanercept to improve efficacy.63
Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.
Biologic therapy adherence, discontinuation, switching, and restarting among patients with psoriasis in the US Medicare population
2016, Journal of the American Academy of Dermatology
Citation Excerpt :
Second, although PDC reflects availability of medication supply, it does not capture whether patients use their medication supply as directed and has the potential to overestimate actual adherence to self-administered medications. Similarly, if prescribers increased the dosing frequency for clinician-administered biologics to overcome loss of response, which has been shown previously for infliximab dosing,33 our calculation of assigned days' supply using the standard dosing schedule would have overestimated adherence if patients missed an interim dose. Third, we were unable to determine whether those who discontinued treatment eventually restarted after our study period ended.
Studies indicate adherence to biologics among patients with psoriasis is low, yet little is known about their use in the Medicare population.
We sought to investigate real-world utilization patterns in a national sample of Medicare beneficiaries with psoriasis initiating infliximab, etanercept, adalimumab, or ustekinumab.
We conducted a retrospective claims analysis using 2009 through 2012 100% Medicare Chronic Condition Data Warehouse Part A, B, and D files, with 12-month follow-up after index prescription. Descriptive and multivariate analyses were used to examine rates of and factors associated with biologic adherence, discontinuation, switching, and restarting.
We examined 2707 patients initiating adalimumab (40.0%), etanercept (37.9%), infliximab (11.7%), and ustekinumab (10.3%); during 12-month follow-up, 38% were adherent and 46% discontinued treatment, with 8% switching to another biologic and 9% later restarting biologic treatment. Being female and being ineligible for low-income subsidies were associated with increased odds of decreased adherence. Outcomes varied by index biologic.
Patient-reported reasons for nonadherence or gaps in treatment are unavailable in claims data.
Medicare patients initiating biologics for psoriasis had low adherence and high discontinuation rates. Further investigation into reasons for inconsistent utilization, including exploration of patient and provider decision-making and barriers to more consistent treatment, is needed.
Bitter apricot essential oil induces apoptosis of human HaCaT keratinocytes
2016, International Immunopharmacology
Citation Excerpt :
Psoriasis, one of the most common human diseases of the skin, is characterized by excessive growth and aberrant differentiation of keratinocytes [1]. Approximately 2% of the global population are affected by psoriasis, and approximately 25% of those with psoriasis experience moderate to severe symptoms [2,3]. An understanding of the symptoms associated with psoriasis is considerably advanced.
Psoriasis is a chronic skin disease that affects approximately 2% of the world's population. Conventional therapeutic approaches are not effective or necessarily safe for treating symptoms due to the serious side effects and resistance to currently prescribed drugs. Traditionally, in oriental medicine, apricot seed (Semen Armeniacae amarum) is used to treat skin diseases. However, the underlying mechanism of action has not been systematically elucidated. In the present study, the anti-proliferative effect of bitter apricot essential oil (BAEO) on cultured HaCaT cells was evaluated and the mechanism of action investigated. BAEO was isolated by hydrodistillation, and gas chromatography–mass spectrometry (GC–MS) analysis identified benzaldehyde (75.35%), benzoic acid (6.21%) and mandelonitrile (5.38%). HaCaT cell growth, measured by sulforhodamine B assay (SRB), was inhibited by BAEO with an IC₅₀ value of 142.45 μg/ml. Apoptosis of HaCaT cells treated with BAEO was detected by cell cycle, flow cytometry, and western blot analyses. These measurements revealed G0/G1 cell cycle arrest, elevated numbers of early and late stage apoptotic cells, and caspases-3/8/9 and PARP activation. Z-VAD-FMK, a broad-spectrum caspase inhibitor, attenuated BAEO-induced apoptosis. Also, increased Bax and decreased Bcl-2 levels suggest that BAEO-induced apoptosis is mediated through both death receptor and mitochondrial pathways. Moreover, reduced Rel/NF-κB levels suggest that BAEO-mediated apoptosis is also associated with inhibition of the NF-κB pathway. These data suggest that BAEO is a naturally occurring material that functions as a potent pro-apoptotic factor for human keratinocytes. Thus, it is a promising candidate to treat psoriasis.
Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: Results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR])
2016, Journal of the American Academy of Dermatology
Comparing effectiveness of biologics in real-world settings will help inform treatment decisions.
We sought to compare therapeutic responses among patients initiating infliximab, adalimumab, or etanercept versus ustekinumab during the Psoriasis Longitudinal Assessment and Registry (PSOLAR).
Proportions of patients achieving a Physician Global Assessment score of clear (0)/minimal (1) and mean decrease in percentage of body surface area with psoriasis were evaluated at 6 and 12 months. Adjusted logistic regression (Physician Global Assessment score 0/1) and analysis of covariance (percentage of body surface area with psoriasis) were performed to determine treatment factors associated with effectiveness.
Of 2541 new users on registry, 2076 had efficacy data: ustekinumab (n = 1041), infliximab (n = 116), adalimumab (n = 662), and etanercept (n = 257). Patients receiving tumor necrosis factor-alpha(-α) inhibitors were significantly less likely to achieve Physician Global Assessment score 0/1 versus ustekinumab (infliximab [odds ratio {OR} 0.396, P < .0001], adalimumab [OR 0.686, P = .0012], etanercept [OR 0.554, P = .0003] at 6 months and infliximab [OR 0.449, P = .0040] at 12 months). Mean decrease in percentage of body surface area with psoriasis was significantly greater for ustekinumab versus adalimumab (point estimate 1.833, P = .0020) and etanercept (point estimate 3.419, P < .0001) at 6 months and versus infliximab (point estimate 3.945, P = .0005) and etanercept (point estimate 2.778, P = .0007) at 12 months.
Treatment selection bias and limited data for doing adjustments are limitations.
In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-α inhibitors studied for the majority of comparisons at 6 and 12 months.
Study on the Key Genes and Molecular Mechanisms of IL-27 Promoting Keratinocytes Proliferation Based on Transcriptome Sequencing
2023, Clinical, Cosmetic and Investigational Dermatology

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: Supported by grant RC1-AR058204 and K24-AR064310 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (Dr Gelfand), National Psoriasis Foundation Fellowship Award (Dr Takeshita), Dermatology Foundation Career Development Award (Dr Takeshita), and Training Grant T32-AR007465 (Mr Shin and Dr Wang) from the National Institutes of Health. The sponsors had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; in the preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.

: Disclosure: Dr Callis Duffin was an investigator, consultant, and/or speaker for AbbVie, Amgen Inc, ApoPharma, Bristol-Myers Squibb, Celgene, Eli Lilly, Genzyme, Incyte, Janssen, NovoNordisk, Pfizer Inc, and Wyeth, receiving honoraria and/or salary; served on the advisory board of Amgen Inc; and received residency/fellowship program funding from AbbVie and Amgen Inc. Dr Gelfand served as a consultant for AbbVie, Amgen Inc, Celgene Corp, Eli Lilly, Janssen, Merck, Novartis Corp, and Pfizer Inc, receiving honoraria; had grants or has pending grants from AbbVie, Amgen Inc, Eli Lilly, Genentech Inc, Novartis Corp, and Pfizer Inc; and received payment for continuing medical education work related to psoriasis. Dr Kalb served as a consultant for AbbVie, Amgen Inc, Janssen, LEO Pharma Inc, and Stiefel Laboratories Inc, receiving honoraria; served as an investigator for AbbVie, Amgen Inc, Astellas Pharma Inc, and Janssen, receiving honoraria; and served as a speaker for AbbVie, Amgen Inc, Galderma Laboratories LP, Janssen, and Stiefel Laboratories Inc. Dr Krueger served as a consultant for AbbVie, Amgen Inc, and Janssen; had grants or has pending grants from AbbVie and Amgen Inc; and received payment for lectures and travel-related expenses from AbbVie, Amgen Inc, and Janssen. Dr Robertson is employed by the National Psoriasis Foundation, which receives unrestricted financial support from companies that make products used to treat psoriasis and psoriatic arthritis, including AbbVie, Amgen Inc, Eli Lilly, Galderma Laboratories LP, Janssen, LEO Pharma Inc, Pfizer Inc, and Stiefel Laboratories Inc. Dr Schleicher has served as an investigator for Eli Lilly and Merck, receiving honoraria and/or salary; and received payment for lectures from Janssen and Aqua Pharmaceuticals. Dr Sperber is the medical director of Stephens and Associates, served as a consultant for Amgen Inc, and had grants or has pending grants from AbbVie and Janssen. Dr Van Voorhees served on advisory boards for AbbVie, Amgen Inc, Celgene, Janssen, LEO Pharma Inc Novartis Corp, Pfizer Inc, and Warner Chilcott; served as an investigator for AbbVie and Amgen Inc, receiving grants; served as a consultant for Amgen Inc; and receives other income from Merck. Dr Weisman had grants or has pending grants from AbbVie, Braintree Laboratories Inc, Celgene Corp, Cipher Pharmaceuticals Inc, and LEO Pharma Inc; and received payments for lectures from AbbVie and Amgen Inc. Drs Takeshita, Wang, Stierstorfer, Brod, Linn, Shinohara, and Troxel, and Mr Shin have no conflicts of interest to declare.

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Original articleComparative effectiveness of less commonly used systemic monotherapies and common combination therapies for moderate to severe psoriasis in the clinical setting

Background

Objective

Methods

Results

Limitations

Conclusions

Section snippets

Study design and participant protection

Results

Discussion

J Am Acad Dermatol

Lancet

J Am Acad Dermatol

J Invest Dermatol

Lancet

Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris

Br J Dermatol

Biologic fatigue in psoriasis

J Dermatolog Treat

Comparative effectiveness of commonly used systemic treatments or phototherapy for moderate to severe plaque psoriasis in the clinical practice setting

Arch Dermatol

Original article
Comparative effectiveness of less commonly used systemic monotherapies and common combination therapies for moderate to severe psoriasis in the clinical setting