584511
research-article2015
CMSXXX10.1177/1203475415584511Journal of Cutaneous Medicine and SurgeryBourcier et al
Basic/Clinical Science
Long-term Management of Moderate to Severe Plaque Psoriasis Patients With Etanercept: A Case Series
Journal of Cutaneous Medicine and Surgery 1–9 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1203475415584511 jcms.sagepub.com
Marc Bourcier1, Kim Alexander Papp2, Wayne P. Gulliver3, Yves Poulin4, Kirk Barber5, Melanie Poulin-Costello6, and Jennifer Shelton6
Abstract Background: Currently, etanercept (ETN) safety and efficacy in patients with moderate to severe plaque psoriasis (PsO) has been reported up to 5 years. Objective: To present a case series of PsO patients receiving continuous ETN therapy for 7 or more years. Methods: Physicians collected data retrospectively from 52 patient charts from 5 centres across Canada. Results: Patients in this case series had PsO an average of 31.5 years. Nearly half of patients also had psoriatic arthritis (24/52). All patients demonstrated sustained improvement in Psoriasis Area and Severity Index (PASI) and percentage of affected body surface area (BSA) following ETN treatment. Of the 52 patients, 33 have been receiving ETN for 10 years or more. Conclusion: The clinical experience described in this case series report suggests maintenance of ETN efficacy in PsO patients who receive therapy for 7 years or more and indicates that patients can be successfully managed with long-term ETN therapy. Résumé Contexte : On a déjà fait état de l’innocuité et l’efficacité de l’étanercept chez des patients atteints de psoriasis en plaques modéré à sévère pour des périodes allant jusqu’à 5 ans. Objectif : Présenter une série de cas de patients atteints de psoriasis en plaques qui ont reçu un traitement continu à l’étanercept pendant 7 ans ou plus. Méthode : Des médecins ont recueilli des données rétrospectivement à partir de 52 dossiers de patients répartis dans 5 centres au Canada. Résultats : Les patients de cette série de cas ont souffert du psoriasis en plaques pendant 31,5 ans en moyenne. Près de la moitié d’entre eux étaient aussi atteints d’arthrite psoriasique (24/52). Tous les patients ont présenté une amélioration durable de l’indice d’étendue et de gravité du psoriasis (Psoriasis Area and Severity Index – PASI) ainsi que du pourcentage de la surface corporelle atteinte après le traitement à l’étanercept. Des 52 patients, 33 prennent de l’étanercept depuis 10 ans ou plus. Conclusion : L’expérience clinique décrite dans ce compte-rendu d’une série de cas indique un maintien de l’efficacité de l’étanercept chez les patients atteints de psoriasis en plaques qui reçoivent le traitement pendant 7 ans ou plus et montre qu’il est possible de gérer avec succès le psoriasis en plaques par un traitement de longue durée à l’étanercept. Keywords psoriatic arthritis, long-term treatment, biologic, case study, case series, etanercept
Introduction Psoriasis (PsO) is a chronic inflammatory disease affecting the skin and joints and is seen in approximately 0.9% to 8.5% of people globally,1 with estimates of the prevalence in the United States reported at 3.2%.2 Plaque PsO is the most common form of PsO, affecting over 80% of PsO patients, and is characterized by abnormal keratinocyte proliferation and infiltration of the skin by activated T cells.Tumour necrosis factor (TNF)-α, which is excessively produced in psoriatic lesions, plays a significant role in PsO pathogenesis.3
1
Sherbrooke University, Sherbrooke, Canada K. Papp Clinical Research and Probity Medical Research, Waterloo, Canada 3 Memorial University of Newfoundland, St. John’s, Canada 4 Centre dermatologique du Quebec metropolitain, Quebec, Canada 5 Dr Kirk Barber Dermatology, Calgary, Canada 6 Amgen Canada Inc, Mississauga, Canada 2
Corresponding Author: Marc Bourcier, Clinique de dermatologie Durondel C.P. Inc, 35 Providence St, Moncton, NB E1C 8X3, Canada. Email: [email protected]
2 Treatment options for PsO vary with disease severity. Approximately 80% of patients with PsO have mild disease that affects less than 2% of their body surface area (BSA), and topical therapies are an effective treatment option for these patients.4 However, approximately 20% of affected patients have moderate to severe PsO that affects over 3% of their BSA.4 These patients are usually treated with systemic treatments: phototherapy, traditional systemic agents, and biological agents. Additionally, topical agents may be used adjunctively with either of the latter treatment options in patients with extensive PsO.5,6 Due to the role of TNF-α in PsO pathogenesis, multiple anti-TNF-α therapies are currently approved for the treatment of moderate to severe plaque PsO. Etanercept (ETN) is a recombinant human soluble TNFreceptor fusion protein that inhibits the interaction of endogenous TNF with cell-surface receptors and as a result prevents its pro-inflammatory activity.7 ETN was first approved for use in Canada in 2000, with approval for the treatment of psoriatic arthritis (PsA) and PsO occurring in 2004 and 2005, respectively.8 The recommended treatment course of ETN in patients with PsO is 50 mg twice weekly (BIW) for 3 months, followed by a maintenance dose of 50 mg once weekly (QW). If required, 50 mg BIW can also be used as a maintenance dose.7 Currently, ETN safety and efficacy in patients with PsO has been reported for up to 5 years of therapy,9 despite the presence of patients who have been treated with ETN well beyond 5 years. Here, we present a case series of PsO patients on continuous ETN therapy for a minimum of 7 years.
Methods Physicians collected data from charts of patients treated with ETN for a minimum of 7 years. All information was collected retrospectively from patient charts. Physicians identified patients on ETN as of 2002 to 2007 and included patients at their practice with ETN use of a minimum of 7 years. Physicians completed an information form for each patient, where the following clinical information was collected: age, sex, year of PsO onset, treatments prior to starting ETN, and ETN start date. ETN dose, concurrent therapies, weight, height, percentage of affected BSA, and Psoriasis Area and Severity Index (PASI) score at baseline and at the time of data collection were also collected. Additional data included PsA status and year of onset, if applicable. No safety data were collected as part of this case series. All results discussed here are descriptive in nature. To our knowledge, none of these patient cases were reported previously in the literature, though some patients in our paper initiated ETN treatment as part of randomized clinical trials. Some data are summarized descriptively across the cohort, where appropriate KaplanMeier methods have been used.
Journal of Cutaneous Medicine and Surgery
Results In total, data from 52 PsO patients were collected from 5 centres across Canada representing 1639 patient-years of follow-up. These patients initiated ETN treatment between 2002 and 2007 and were treated until at least 2011 to 2014, for a total of at least 511 patient-years of ETN treatment. The duration of PsO averaged 31.5 years (range, 9-72 years), with a median of 29.0 years. ETN treatment was initiated an average of 21.7 years (range, 1-62 years) following PsO diagnosis, with a median of 19.5 years (Figure 1, Table 1). The exact date of PsO diagnosis is unknown for 2 patients (patient Nos. 15 and 16). These patients are known to have been diagnosed prior to 1991, approximately 22 years before data collection (Figure 1). With the exception of 1 patient (patient No. 46), all patients were diagnosed with PsO prior to ETN availability in Canada. Of the 52 patients, 24 (46.2%) were diagnosed with PsA (Table 1). The PsA status of 4 patients is unknown (patient Nos. 32-35). Furthermore, the exact date of PsA diagnosis is unknown for 2 patients (patients Nos. 13 and 14); however, both were diagnosed before starting ETN therapy, approximately 8 and 9 years prior to data collection, respectively (Table 1). With the exception of 1 patient (patient No. 49), who was diagnosed with PsA 1 year before PsO, all patients were diagnosed with PsA the same year they received their PsO diagnosis, or later. All but 2 patients (patient Nos. 4 and 52) were diagnosed with PsA before commencing ETN therapy. Patient No. 4 and patient No. 52 were diagnosed with PsA after 10 and 3 years of ETN therapy, respectively. The average time to ETN therapy following a PsA diagnosis was 13.9 years, with a median of 14 years. The time to PsA diagnosis following PsO diagnosis ranged from 0 (simultaneous diagnosis) to 34.9 years, with a median of 34.9 years (Figure 1). Up until the time of data collection, the total duration of PsA among those patients diagnosed with PsA ranged from 0.1 to 38 years, with an average of 18.1 years and median of 17.5 years (Table 1). In all patients, PASI score and percentage of affected BSA for each patient at data collection were substantially lower than baseline after 7 to >10 years of ETN treatment (Figures 2A and 2B). The average baseline PASI score was 20.5 (8.6-39.8), while PASI scores at data collection averaged 1.7 (0-7.4). Percentage of affected BSA also demonstrated a reduction from a baseline average of 21.8% (10%-68%) to an average of 1.4% (0%-6%) at data collection. In PsA patients, average PASI score and percentage of affected BSA at data collection were similar to all the patients in this case series, at 1.9 (0-7.4) and 1.7% (0%-6%), respectively. Prior to receiving ETN treatment, 46 of 52 (88.5%) patients received topical therapy, 28 of 52 (53.8%) received phototherapy, 34 of 52 (65.4%) received systemic therapy, and 10 of 52 (19.2%) were treated with a biologic (Table 2). Most patients initiated ETN therapy prior to any other
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Bourcier et al
Figure 1. Duration of PsO, PsA, and etanercept therapy.
Duration of PsO, in years, is depicted for each patient via a dotted line. Patients are ordered from shortest duration of PsO on the left (9 years) to longest duration of PsO on the right (72 years). The number of years since ETN initiation is denoted for each of the patients via the open triangle, whereas the closed circle denotes the number of years since PsA diagnosis, where applicable. Correlating patient numbers are found on the x-axis. ETN, etanercept; PsA, psoriatic arthritis; PsO, psoriasis. a PsA diagnosis earlier but exact date unknown. b Duration of disease is approximate. c Diagnosis of PsA is unknown.
biologics being available in Canada. Some of these patients initiated ETN as part of a clinical trial. In addition to ETN, 13 of 52 (25%) patients received concomitant topical therapy at data collection, with 2 of 52 (3.8%) and 3 of 52 (5.8%) receiving phototherapy and systemic therapy, respectively. Of the patients using concomitant topical therapy, some patients used it as part of their regular treatment regimen, while the majority used it during flares on an as needed basis. The majority of patients (31/52, 59.6%) received an ETN dose of 50 mg QW at data collection, while other ETN administered doses included 100 mg QW (9/52; 17.3%), 50 mg BIW (7/52; 13.5%), 25 mg QW (3/52; 5.8%), and 50 mg every 2 weeks (Q2W; 2/52; 3.9%). At the time of data collection, 33 (63.5%) of 52 patients in this case series were on ETN therapy for 10 years or more, 17 (51.5%) of which have a PsA diagnosis and 2 (6%) have an unknown PsA status (Table 3). Percentage of affected BSA and PASI score in this population averaged 1.3% (0%-5%) and 1.7 (0-6) at data collection, respectively. Most patients (19/33, 57.6%) received an ETN dose of 50 mg QW, with 6 of 33 (18.2%) receiving 100 mg QW, 7 of 33 (21.2%) receiving 50 mg BIW, and 1 of 33 (3.0%) receiving 50 mg Q2W.
Discussion This paper presents a case series of PsO patients on continuous ETN therapy for a minimum of 7 years, which, to our knowledge, provides some of the most long-term descriptive data available regarding PsO patient disease history and status. Patients in this case series had PsO for an average of 31.5 years, nearly half of which have PsA. All patients demonstrated sustained improvement in PASI score and percentage of affected BSA, and almost all patients received topical therapy or systemic therapy before initiating ETN. More than half of patients from this case series were on ETN treatment for 10 years or more.
Long-term Efficacy of ETN in Psoriasis ETN has demonstrated a favourable safety and efficacy profile in both short- and longer-term (≤4 years) clinical trials conducted in adult patients with moderate to severe plaque PsO. In 2 randomized, double-blind, placebo-controlled, multicenter, phase III clinical trials, significantly more patients treated with ETN achieved PASI75 (75% reduction in PASI score) compared with patients receiving placebo, and the
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Table 1. Patient Demographics and Disease and Treatment Duration.a Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52
Age (y)
Sex
64 63 54 64 57 49 53 82 50 48 59 43 57 64 64 71 54 47 67 38 61 56 51 66 56 81 63 38 55 70 52 58 63 53 67 59 49 38 63 62 32 67 71 50 51 47 57 46 70 69 65 40
M M M M M F M F F M F M F M M M M M F F M M M F F M M M F M M M M M M M M F F M M M M F F M F M M M M M
Baseline BMI (kg/m2)
Current BMI (kg/m2)
29 24 27 25 23 25 17 37 25 32
27 27 27 29 25 25 14 37 27
b
b
33 30 37 31 45 26 32 35 29 31 31 38 34 38 25 44
25 24 30 33 32 35 32 41 33 43 26 30 34 29 36 31 47 36 30 25 53
b
b
b
b
b
b
b
b
27 28 24 28 37 37 30 34 35 28 21 30 21 37 33 32
31 31 27 32 38 39 31 35 42 29 22 28 22 35 29 31
b b b b
b
b
PsO Duration
ETN Duration (s)
PsA Duration (y)
24 33 34 35 35 44 29 20 45 29 21 28 20 22 ≥22 ≥22 29 22 61 23 27 48 36 25 44 72 39 23 34 38 30 28 53 43 38 33 30 29 43 14 17 30 51 25 24 9 37 25 37 14 27 18
10 11 9 10 11 11 11 10 9 11 8 12 8 9 9 7 10 11 11 11 10 8 9 7 10 10 11 11 11 10 10 7 8 10 10 9 12 9 9 10 7 11 11 11 7 8 9 12 10 12 12 11
N/A N/A N/A 0.08 23 N/A N/A 20 N/A N/A N/A N/A ≥8 ≥9 N/A N/A 18 N/A 27 19 20 15 N/A 16 N/A N/A 26 16 13 20 29
Abbreviations: BMI, body mass index; ETN, etanercept; F, female; M, male; N/A, not applicable; PsA, psoriatic arthritis. a All patients were Caucasian. b Data unavailable.
b b b b
N/A N/A N/A 27 N/A N/A N/A 25 15 17 9 N/A 16 38 N/A N/A 8
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Bourcier et al
Figure 2. Disease characteristics at baseline and data collection.
Panel A shows percentage of affected BSA at baseline and at time of data collection for all patients. Panel B shows PASI score at baseline and at time of data collection. Both panels present patient data in order of patient number, from 1 to 52. *Baseline PASI for patient No. 11 was unavailable. BSA, body surface area; PASI, Psoriasis Area and Severity Index.
therapeutic effect was dose-dependent.10,11 Furthermore, several short-term trials (12-24 weeks) with open-label extensions were also able to demonstrate longer-term safety and efficacy of ETN in patients with PsO for up to 2.5 years.12,13 Lastly, results from OBSERVE-5, a 5-year observational registry, demonstrated that ETN efficacy, as measured by psoriasis-affected BSA improvement, static Physician’s Global Assessment (sPGA), and Dermatology Life Quality Index (DLQI) response, was sustained for up to 5 years.9 In this case series, improvements in PASI from baseline were maintained long-term, as these patients have currently
received treatment for up to 10 years or more. Percentage of affected BSA also showed sustained improvement from baseline in these patients.
PsO Patients Treated With ETN for 10 Years or More Currently, ETN safety and efficacy data in patients with PsO has only been reported for up to 5 years of therapy, despite there being patients who have been on ETN therapy for over 10 years. At the time of data collection, more than half of the
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Table 2. Therapy Prior to and During Etanercept Treatment. Treatments Prior to Starting ETN Patient No.
Topical Therapy
Phototherapy
Systemic Therapy
Current ETN Dose
Biologic Treatments
25 mg QW
50 mg QW
50 mg Q2W
50 mg BIW
Current Concomitant Therapy 100 mg QW
Topical Therapy
Phototherapy
Systemic Therapy
1
•
•
•
2
•
•
•
•
•
•a
3
•
4
•
5
•
•
•a
6
•
•
•a,c
•
d
•
a,c
7
•
• •
8
•
•
9
•
•
10
•
•
11
•
•
•
•b
• •e
•
•a,c,f,g
•b
•
a,d
b
•
•
•
•
•
•
•
13
•
•
•a
•h
14
•
•
•a
15
•
•
•a
16
•
•
•c,g
17
•
•
18
•
•
•
• •e
• •
•
•
•
•
• •a,g
• g
21
•
•
•
22
•
•
•a,g
23
•
•
24
•
•
25
•
•a,g
•
•
•a
•
•
•b
g
•
19 •
• •
12
20
•
•
•
•
•
•
26
•
•
•
27
•
•
•a,g
28
•
•g
•
•
a,g
•
g
•
29
• •b
•
30
•
•
•
31
•
•
•a
•
•a
•
33
•
a
•
•
34
•
•a,c
•
35
•
a
•
•
36
•
•a,d
•
i
•
32
37
•
•
38
•
•i
39
•
40
•
41
•
42
•
43
•
•
•i i
•
•i
•
•g
•
•
•
•
•i
•
•
•
•
•
•
(continued)
7
Bourcier et al Table 2. (continued) Treatments Prior to Starting ETN Patient No. 44
Topical Therapy
Phototherapy
Systemic Therapy
Biologic Treatments
Current ETN Dose 25 mg QW
50 mg QW
• i
45
•
•
46
•
•i
47
•
48
•
49
•
•
50
•
•
51
•
52
•
50 mg Q2W
50 mg BIW
Current Concomitant Therapy 100 mg QW
Phototherapy
Systemic Therapy
•
•
•
•
•
•
Topical Therapy
•
•
•
•
Abbreviations: BIW, twice weekly; ETN, etanercept; QW, weekly; Q2W, once every other week. a Methotrexate. b Alefacept. c Cyclosporine. d Voclosporin. e Efalizumab. f Mycophenolate mofetil. g Retinoid. h Infliximab. i Name of medication not specified.
cases had been receiving ETN treatment for 10 years or more. PASI scores and percentage of affected BSA showed sustained improvement in all of these patients, with an average PASI score and percentage of affected BSA of 1.7 and 1.4% at data collection, respectively.
Prior and Concomitant PsO Treatments PsO therapy ranges from topical treatment for patients with mild disease to systemic, targeted, or phototherapy for patients with moderate to severe disease. Table 2 lists the treatments used by the 52 patients described in this report prior to starting ETN therapy and the current treatments used concomitantly with ETN. In general, topical therapies are used in patients with localized PsO, with topical corticosteroid therapy being the most common and convenient treatment.5 Alternatives to topical corticosteroids are vitamin D analogs, including calcipotriene, calcitriol, and tacalcitol. In many cases, topical therapies are used concomitantly in patients who are undergoing systemic, targeted, or phototherapy.5 In this case series, 46 of 52 (88.4%) patients received topical therapy prior to receiving ETN, while at data collection, 13 of 52 (25%) patients received topical therapy concurrently with ETN treatment. Phototherapy is a treatment option for patients with PsO that is refractory to topical agents or too widespread to treat with topical therapy. Broadband UVB (BBUVB) phototherapy, narrowband UVB (NBUVB), and PUVA photochemotherapy can be used on select patients. Prior to initiating ETN treatment, 28 of 52 (53.8%) patients received phototherapy. At the time of
data collection, 2 patients (Nos. 16 and 38) received phototherapy in addition to ETN, while patient No. 16 also received additional topical therapy. Another alternative to topical therapy in the case of refractoriness and/or widespread PsO or lack of response to phototherapy is systemic therapy. Traditional systemic therapy agents include methotrexate (MTX), retinoids, and cyclosporine. These medications have potential toxicities that may limit their use. In this case series, prior to starting ETN, 34 of 52 (65.3%) patients received systemic therapy. At data collection, 2 patients (Nos. 4 and 19) received MTX in addition to ETN. Patient No. 32 also received a retinoid, and patient Nos. 4 and 32 also received topical therapy. Combining phototherapy with ETN is an effective treatment option that can accelerate the clearance of psoriatic lesions in ETN-treated patients with PsO.14-17 Two patients used phototherapy concomitantly with ETN at the start of therapy and up until data collection. Combination therapy involving ETN with MTX has also shown good efficacy in PsO patients.18 Two patients in this report were treated with ETN and MTX (Nos. 4 and 19). One patient (No. 32) was treated with ETN and a retinoid in addition to a topical therapy, though no patients received cyclosporine in combination with ETN.
PsA PsA is a seronegative arthritis that affects up to 30% of patients with plaque PsO19; however, the risk of developing PsA appears to be associated with the extent of skin PsO.20 The safety and efficacy of ETN for the treatment of PsA has
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Table 3. PsO Patients on Etanercept Over 10 Years.a Duration PsO of ETN Patient No. Age (y) Sex Duration (y) Therapy (y) 1 2 4 5 6 7 8 10 12 17 18 19 20 21 25 26 27 28 29 30 31 34 35 37 40 42 43 44 48 49 50 51 52
64 63 64 57 49 53 82 48 43 54 47 67 38 61 56 81 63 38 55 70 52 53 67 49 62 67 71 50 46 70 69 65 40
M M M M F M F M M M M F F M F M M M F M M M M M M M M F M M M M M
24 33 35 35 44 29 20 29 28 29 22 61 23 27 44 72 39 23 34 38 30 43 38 30 14 30 51 25 25 37 14 27 18
10 11 10 11 11 11 10 11 12 10 11 11 11 10 10 10 11 11 11 10 10 10 10 12 10 11 11 11 12 10 12 12 11
Baseline Dose
Current Dose
50 mg BIW 50 mg BIW 50 mg BIW 25 mg BIW 25 mg BIW 25 mg BIW 50 mg BIW 25 mg BIW 50 mg BIW 50 mg BIW 25 mg BIW 25 mg BIW 25 mg BIW 25 mg BIW 50 mg BIW 50 mg BIW 25 mg BIW 50 mg BIW 25 mg BIW 50 mg BIW 50 mg BIW 50 mg BIW 50 mg BIW
50 mg BIW 50 mg BIW 50 mg BIW 50 mg QW 50 mg QW 50 mg Q2W 50 mg QW 50 mg BIW 50 mg QW 50 mg QW 50 mg BIW 50 mg QW 50 mg QW 25 mg QW 50 mg QW 50 mg QW 50 mg BIW 50 mg QW 50 mg QW 50 mg QW 50 mg BIW 50 mg QW 50 mg QW 50 mg QW 100 mg QW 50 mg QW 100 mg QW 100 mg QW 100 mg QW 50 mg QW 100 mg QW 100 mg QW 50 mg QW
b b b b b b b b b b
Baseline Current Baseline Current PsA BSA (%) BSA (%) PASI PASI Duration (y) 10 11 13 50 23 22 15 12 40 13 36 18 28 15 14 34 45 26 12 11 68 20 15 15 21 19 16 15 11 30 22 28 31
0.7 0.2 0.5 1 0 3 4 0 0.4 0 2.5 0.5 4 1 1 1 3 1.5 0 2.5 5 1 2 2 1 0.1 0.2 1 0.5 0.1 2 0.2 1
16.4 14.4 13.2 29.2 26.5 18 15.7 15 28.2 13.2 26.5 11.4 16.9 15.4 12.8 23.4 22.3 25.2 12.2 16.6 39.8 15 18 22 38 26 18 23 16 35 27 35 27
1.8 0.6 0.6 1.6 0 6 3 0 1.2 0 4.2 0.5 5.2 2 1.8 3.2 3.2 1.8 0 2 3.2 1.2 1.8 2 0.6 0.4 1.3 1.4 1.1 2.3 1.8 0.7 0.5
N/A N/A 0.08 23 N/A N/A 20 N/A N/A 18 N/A 27 19 20 N/A N/A 26 16 13 20 29 b b
N/A N/A N/A 25 15 16 38 N/A N/A 8
Abbreviations: BIW, twice weekly; BSA, body surface area; ETN, etanercept; F, female; M, male; N/A, not applicable; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsO, psoriasis; QW, once weekly; Q2W, once every other week. a All patients were Caucasian. b Data unknown.
been demonstrated in several short-term (≤24 weeks) studies and an open-label extension study that followed patients up to 2 years.21,22 In this case series, 46.2% (24/52) of patients developed PsA. With the exception of 2 patients, PsA diagnosis preceded ETN therapy. In Canada, ETN is approved for the treatment of PsA with a starting dose of 50 mg QW, which is the dose received by most of the patients with PsA in this case series (13/24; 54.2%).
Conclusion The clinical experience described in this descriptive case series suggests maintenance of ETN efficacy in patients
with PsO receiving therapy for 7 years or more and indicates that patients can be successfully managed with longterm ETN therapy. Furthermore, this long-term efficacy was also demonstrated in patients with PsA. Further study of a greater number of PsO patients receiving long-term (≥7 years) ETN treatment may be able to more completely illuminate efficacy and safety of ETN in this patient population. Acknowledgments We thank Jessica Benzaquen, MSc, and Julia Swiercz, PhD, from Synapse Medical Communications, Oakville, Ontario, who provided medical writing assistance in the form of drafting
Bourcier et al and revising as per authors’ directions and in accordance with the standards set out by the International Committee of Medical Journal Editors.
Authors’ Note Amgen Canada Inc oversaw the design, conduct, and collection of data in the manuscript and assisted in the analysis and interpretation of data.
Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Marc Bourcier received honorariums for advisory boards and grants for clinical trials: AbbVie, Actelion, Amgen, Astellas, Novartis, Leo, Janssen, Merck, and Pfizer. Kim Papp is a consultant, on advisory boards, participates in speaker’s bureaus, and is an investigator for Amgen. Wayne Gulliver received honoraria for consultant services from Amgen. Yves Poulin received honoraria for lectures and/or research grants from Abbvie, Actelion, Amgen, Boehringer, Celgene, Eli-Lilly, Galderma, Incyte, Janssen, LeoPharma, Merck, Novartis, Pfizer, Schering, and Takeda. Kirk Barber received honoraria for consultant services from Amgen. Melanie Poulin-Costello and Jennifer Shelton are employees of Amgen Canada.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This manuscript was supported in part by Amgen Canada Inc.
References 1. Parisi R, Symmons DP, Griffiths CE, et al. Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133:377-385. 2. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516. 3. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 2007;445:866-873. 4. Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis patients in US adults: results from NHANES 2003-2004. J Am Acad Dermatol. 2009;60:218-224. 5. Papp K, Gulliver W, Lynde C, et al. Canadian Psoriasis Guidelines Committee. Canadian guidelines for the management of plaque psoriasis: overview. J Cutan Med Surg. 2011;15:210-219. 6. Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol. 2009;23(suppl 2):1-70. 7. ENBREL (etanercept). Product Monograph. Mississauga, Canada: Amgen Canada Inc; 2013.
9 8. Health Canada. Notice of Compliance (NOC) database—drug products. http://www.hc-sc.gc.ca/dhp-mps/prodpharma/noticesavis/noc-acc/index-eng.php. Accessed November, 26, 2014. 9. Kimball AB, Rothman KJ, Kricorian G, et al. OBSERVE-5: observational postmarketing safety and surveillance registry of etanercept for the treatment of psoriasis final 5-year results. J Am Acad Dermatol. 2015;72(1):115-122. 10. Leonardi CL, Powers JL, Matheson RT, et al. Etanercept Psoriasis Study Group. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349:2014-2022. 11. Papp KA, Tyring S, Lahfa M, et al. Etanercept Psoriasis Study Group. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol. 2005;152:1304-1312. 12. Leonardi C, Strober B, Gottlieb AB, et al. Long-term safety and efficacy of etanercept in patients with psoriasis: an openlabel study. J Drugs Dermatol. 2010;9(8):928-937. 13. Tyring S, Gordon KB, Poulin Y, et al. Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis. Arch Dermatol. 2007;143:719-726. 14. Kircik L, Bagel J, Korman N, et al. Unite Study Group. Utilization of narrow-band ultraviolet light B therapy and etanercept for the treatment of psoriasis (UNITE): efficacy, safety, and patient-reported outcomes. J Drugs Dermatol. 2008;7:245-253. 15. Gambichler T, Tigges C, Scola N, et al. Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks. Br J Dermatol. 2011;164:1383-1386. 16. Wolf P, Hofer A, Legat FJ, et al. Treatment with 311-nm ultraviolet B accelerates and improves the clearance of psoriatic lesions in patients treated with etanercept. Br J Dermatol. 2009;160:186-189. 17. De Simone C, D’Agostino M, Capizzi R, et al. Combined treatment with etanercept 50 mg once weekly and narrow-band ultraviolet B phototherapy in chronic plaque psoriasis. Eur J Dermatol. 2011;21:568-572. 18. Gottlieb AB, Langley RG, Strober BE, et al. A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis. Br J Dermatol. 2012;167:649-657. 19. Zachariae H, Zachariae R, Blomqvist K, et al. Quality of life and prevalence of arthritis reported by 5,795 members of the Nordic Psoriasis Associations. Data from the Nordic Quality of Life Study. Acta Derm Venereol. 2002;82:108-113. 20. Gelfand JM, Gladman DD, Mease PJ, et al. Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol. 2005;53:573. 21. Mease PJ, Goffe BS, Metz J, et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet. 2000;356:385-390. 22. Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50:2264-2272.
research-article2015
CMSXXX10.1177/1203475415584511Journal of Cutaneous Medicine and SurgeryBourcier et al
Basic/Clinical Science
Long-term Management of Moderate to Severe Plaque Psoriasis Patients With Etanercept: A Case Series
Journal of Cutaneous Medicine and Surgery 1–9 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1203475415584511 jcms.sagepub.com
Marc Bourcier1, Kim Alexander Papp2, Wayne P. Gulliver3, Yves Poulin4, Kirk Barber5, Melanie Poulin-Costello6, and Jennifer Shelton6
Abstract Background: Currently, etanercept (ETN) safety and efficacy in patients with moderate to severe plaque psoriasis (PsO) has been reported up to 5 years. Objective: To present a case series of PsO patients receiving continuous ETN therapy for 7 or more years. Methods: Physicians collected data retrospectively from 52 patient charts from 5 centres across Canada. Results: Patients in this case series had PsO an average of 31.5 years. Nearly half of patients also had psoriatic arthritis (24/52). All patients demonstrated sustained improvement in Psoriasis Area and Severity Index (PASI) and percentage of affected body surface area (BSA) following ETN treatment. Of the 52 patients, 33 have been receiving ETN for 10 years or more. Conclusion: The clinical experience described in this case series report suggests maintenance of ETN efficacy in PsO patients who receive therapy for 7 years or more and indicates that patients can be successfully managed with long-term ETN therapy. Résumé Contexte : On a déjà fait état de l’innocuité et l’efficacité de l’étanercept chez des patients atteints de psoriasis en plaques modéré à sévère pour des périodes allant jusqu’à 5 ans. Objectif : Présenter une série de cas de patients atteints de psoriasis en plaques qui ont reçu un traitement continu à l’étanercept pendant 7 ans ou plus. Méthode : Des médecins ont recueilli des données rétrospectivement à partir de 52 dossiers de patients répartis dans 5 centres au Canada. Résultats : Les patients de cette série de cas ont souffert du psoriasis en plaques pendant 31,5 ans en moyenne. Près de la moitié d’entre eux étaient aussi atteints d’arthrite psoriasique (24/52). Tous les patients ont présenté une amélioration durable de l’indice d’étendue et de gravité du psoriasis (Psoriasis Area and Severity Index – PASI) ainsi que du pourcentage de la surface corporelle atteinte après le traitement à l’étanercept. Des 52 patients, 33 prennent de l’étanercept depuis 10 ans ou plus. Conclusion : L’expérience clinique décrite dans ce compte-rendu d’une série de cas indique un maintien de l’efficacité de l’étanercept chez les patients atteints de psoriasis en plaques qui reçoivent le traitement pendant 7 ans ou plus et montre qu’il est possible de gérer avec succès le psoriasis en plaques par un traitement de longue durée à l’étanercept. Keywords psoriatic arthritis, long-term treatment, biologic, case study, case series, etanercept
Introduction Psoriasis (PsO) is a chronic inflammatory disease affecting the skin and joints and is seen in approximately 0.9% to 8.5% of people globally,1 with estimates of the prevalence in the United States reported at 3.2%.2 Plaque PsO is the most common form of PsO, affecting over 80% of PsO patients, and is characterized by abnormal keratinocyte proliferation and infiltration of the skin by activated T cells.Tumour necrosis factor (TNF)-α, which is excessively produced in psoriatic lesions, plays a significant role in PsO pathogenesis.3
1
Sherbrooke University, Sherbrooke, Canada K. Papp Clinical Research and Probity Medical Research, Waterloo, Canada 3 Memorial University of Newfoundland, St. John’s, Canada 4 Centre dermatologique du Quebec metropolitain, Quebec, Canada 5 Dr Kirk Barber Dermatology, Calgary, Canada 6 Amgen Canada Inc, Mississauga, Canada 2
Corresponding Author: Marc Bourcier, Clinique de dermatologie Durondel C.P. Inc, 35 Providence St, Moncton, NB E1C 8X3, Canada. Email: [email protected]
2 Treatment options for PsO vary with disease severity. Approximately 80% of patients with PsO have mild disease that affects less than 2% of their body surface area (BSA), and topical therapies are an effective treatment option for these patients.4 However, approximately 20% of affected patients have moderate to severe PsO that affects over 3% of their BSA.4 These patients are usually treated with systemic treatments: phototherapy, traditional systemic agents, and biological agents. Additionally, topical agents may be used adjunctively with either of the latter treatment options in patients with extensive PsO.5,6 Due to the role of TNF-α in PsO pathogenesis, multiple anti-TNF-α therapies are currently approved for the treatment of moderate to severe plaque PsO. Etanercept (ETN) is a recombinant human soluble TNFreceptor fusion protein that inhibits the interaction of endogenous TNF with cell-surface receptors and as a result prevents its pro-inflammatory activity.7 ETN was first approved for use in Canada in 2000, with approval for the treatment of psoriatic arthritis (PsA) and PsO occurring in 2004 and 2005, respectively.8 The recommended treatment course of ETN in patients with PsO is 50 mg twice weekly (BIW) for 3 months, followed by a maintenance dose of 50 mg once weekly (QW). If required, 50 mg BIW can also be used as a maintenance dose.7 Currently, ETN safety and efficacy in patients with PsO has been reported for up to 5 years of therapy,9 despite the presence of patients who have been treated with ETN well beyond 5 years. Here, we present a case series of PsO patients on continuous ETN therapy for a minimum of 7 years.
Methods Physicians collected data from charts of patients treated with ETN for a minimum of 7 years. All information was collected retrospectively from patient charts. Physicians identified patients on ETN as of 2002 to 2007 and included patients at their practice with ETN use of a minimum of 7 years. Physicians completed an information form for each patient, where the following clinical information was collected: age, sex, year of PsO onset, treatments prior to starting ETN, and ETN start date. ETN dose, concurrent therapies, weight, height, percentage of affected BSA, and Psoriasis Area and Severity Index (PASI) score at baseline and at the time of data collection were also collected. Additional data included PsA status and year of onset, if applicable. No safety data were collected as part of this case series. All results discussed here are descriptive in nature. To our knowledge, none of these patient cases were reported previously in the literature, though some patients in our paper initiated ETN treatment as part of randomized clinical trials. Some data are summarized descriptively across the cohort, where appropriate KaplanMeier methods have been used.
Journal of Cutaneous Medicine and Surgery
Results In total, data from 52 PsO patients were collected from 5 centres across Canada representing 1639 patient-years of follow-up. These patients initiated ETN treatment between 2002 and 2007 and were treated until at least 2011 to 2014, for a total of at least 511 patient-years of ETN treatment. The duration of PsO averaged 31.5 years (range, 9-72 years), with a median of 29.0 years. ETN treatment was initiated an average of 21.7 years (range, 1-62 years) following PsO diagnosis, with a median of 19.5 years (Figure 1, Table 1). The exact date of PsO diagnosis is unknown for 2 patients (patient Nos. 15 and 16). These patients are known to have been diagnosed prior to 1991, approximately 22 years before data collection (Figure 1). With the exception of 1 patient (patient No. 46), all patients were diagnosed with PsO prior to ETN availability in Canada. Of the 52 patients, 24 (46.2%) were diagnosed with PsA (Table 1). The PsA status of 4 patients is unknown (patient Nos. 32-35). Furthermore, the exact date of PsA diagnosis is unknown for 2 patients (patients Nos. 13 and 14); however, both were diagnosed before starting ETN therapy, approximately 8 and 9 years prior to data collection, respectively (Table 1). With the exception of 1 patient (patient No. 49), who was diagnosed with PsA 1 year before PsO, all patients were diagnosed with PsA the same year they received their PsO diagnosis, or later. All but 2 patients (patient Nos. 4 and 52) were diagnosed with PsA before commencing ETN therapy. Patient No. 4 and patient No. 52 were diagnosed with PsA after 10 and 3 years of ETN therapy, respectively. The average time to ETN therapy following a PsA diagnosis was 13.9 years, with a median of 14 years. The time to PsA diagnosis following PsO diagnosis ranged from 0 (simultaneous diagnosis) to 34.9 years, with a median of 34.9 years (Figure 1). Up until the time of data collection, the total duration of PsA among those patients diagnosed with PsA ranged from 0.1 to 38 years, with an average of 18.1 years and median of 17.5 years (Table 1). In all patients, PASI score and percentage of affected BSA for each patient at data collection were substantially lower than baseline after 7 to >10 years of ETN treatment (Figures 2A and 2B). The average baseline PASI score was 20.5 (8.6-39.8), while PASI scores at data collection averaged 1.7 (0-7.4). Percentage of affected BSA also demonstrated a reduction from a baseline average of 21.8% (10%-68%) to an average of 1.4% (0%-6%) at data collection. In PsA patients, average PASI score and percentage of affected BSA at data collection were similar to all the patients in this case series, at 1.9 (0-7.4) and 1.7% (0%-6%), respectively. Prior to receiving ETN treatment, 46 of 52 (88.5%) patients received topical therapy, 28 of 52 (53.8%) received phototherapy, 34 of 52 (65.4%) received systemic therapy, and 10 of 52 (19.2%) were treated with a biologic (Table 2). Most patients initiated ETN therapy prior to any other
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Bourcier et al
Figure 1. Duration of PsO, PsA, and etanercept therapy.
Duration of PsO, in years, is depicted for each patient via a dotted line. Patients are ordered from shortest duration of PsO on the left (9 years) to longest duration of PsO on the right (72 years). The number of years since ETN initiation is denoted for each of the patients via the open triangle, whereas the closed circle denotes the number of years since PsA diagnosis, where applicable. Correlating patient numbers are found on the x-axis. ETN, etanercept; PsA, psoriatic arthritis; PsO, psoriasis. a PsA diagnosis earlier but exact date unknown. b Duration of disease is approximate. c Diagnosis of PsA is unknown.
biologics being available in Canada. Some of these patients initiated ETN as part of a clinical trial. In addition to ETN, 13 of 52 (25%) patients received concomitant topical therapy at data collection, with 2 of 52 (3.8%) and 3 of 52 (5.8%) receiving phototherapy and systemic therapy, respectively. Of the patients using concomitant topical therapy, some patients used it as part of their regular treatment regimen, while the majority used it during flares on an as needed basis. The majority of patients (31/52, 59.6%) received an ETN dose of 50 mg QW at data collection, while other ETN administered doses included 100 mg QW (9/52; 17.3%), 50 mg BIW (7/52; 13.5%), 25 mg QW (3/52; 5.8%), and 50 mg every 2 weeks (Q2W; 2/52; 3.9%). At the time of data collection, 33 (63.5%) of 52 patients in this case series were on ETN therapy for 10 years or more, 17 (51.5%) of which have a PsA diagnosis and 2 (6%) have an unknown PsA status (Table 3). Percentage of affected BSA and PASI score in this population averaged 1.3% (0%-5%) and 1.7 (0-6) at data collection, respectively. Most patients (19/33, 57.6%) received an ETN dose of 50 mg QW, with 6 of 33 (18.2%) receiving 100 mg QW, 7 of 33 (21.2%) receiving 50 mg BIW, and 1 of 33 (3.0%) receiving 50 mg Q2W.
Discussion This paper presents a case series of PsO patients on continuous ETN therapy for a minimum of 7 years, which, to our knowledge, provides some of the most long-term descriptive data available regarding PsO patient disease history and status. Patients in this case series had PsO for an average of 31.5 years, nearly half of which have PsA. All patients demonstrated sustained improvement in PASI score and percentage of affected BSA, and almost all patients received topical therapy or systemic therapy before initiating ETN. More than half of patients from this case series were on ETN treatment for 10 years or more.
Long-term Efficacy of ETN in Psoriasis ETN has demonstrated a favourable safety and efficacy profile in both short- and longer-term (≤4 years) clinical trials conducted in adult patients with moderate to severe plaque PsO. In 2 randomized, double-blind, placebo-controlled, multicenter, phase III clinical trials, significantly more patients treated with ETN achieved PASI75 (75% reduction in PASI score) compared with patients receiving placebo, and the
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Journal of Cutaneous Medicine and Surgery
Table 1. Patient Demographics and Disease and Treatment Duration.a Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52
Age (y)
Sex
64 63 54 64 57 49 53 82 50 48 59 43 57 64 64 71 54 47 67 38 61 56 51 66 56 81 63 38 55 70 52 58 63 53 67 59 49 38 63 62 32 67 71 50 51 47 57 46 70 69 65 40
M M M M M F M F F M F M F M M M M M F F M M M F F M M M F M M M M M M M M F F M M M M F F M F M M M M M
Baseline BMI (kg/m2)
Current BMI (kg/m2)
29 24 27 25 23 25 17 37 25 32
27 27 27 29 25 25 14 37 27
b
b
33 30 37 31 45 26 32 35 29 31 31 38 34 38 25 44
25 24 30 33 32 35 32 41 33 43 26 30 34 29 36 31 47 36 30 25 53
b
b
b
b
b
b
b
b
27 28 24 28 37 37 30 34 35 28 21 30 21 37 33 32
31 31 27 32 38 39 31 35 42 29 22 28 22 35 29 31
b b b b
b
b
PsO Duration
ETN Duration (s)
PsA Duration (y)
24 33 34 35 35 44 29 20 45 29 21 28 20 22 ≥22 ≥22 29 22 61 23 27 48 36 25 44 72 39 23 34 38 30 28 53 43 38 33 30 29 43 14 17 30 51 25 24 9 37 25 37 14 27 18
10 11 9 10 11 11 11 10 9 11 8 12 8 9 9 7 10 11 11 11 10 8 9 7 10 10 11 11 11 10 10 7 8 10 10 9 12 9 9 10 7 11 11 11 7 8 9 12 10 12 12 11
N/A N/A N/A 0.08 23 N/A N/A 20 N/A N/A N/A N/A ≥8 ≥9 N/A N/A 18 N/A 27 19 20 15 N/A 16 N/A N/A 26 16 13 20 29
Abbreviations: BMI, body mass index; ETN, etanercept; F, female; M, male; N/A, not applicable; PsA, psoriatic arthritis. a All patients were Caucasian. b Data unavailable.
b b b b
N/A N/A N/A 27 N/A N/A N/A 25 15 17 9 N/A 16 38 N/A N/A 8
5
Bourcier et al
Figure 2. Disease characteristics at baseline and data collection.
Panel A shows percentage of affected BSA at baseline and at time of data collection for all patients. Panel B shows PASI score at baseline and at time of data collection. Both panels present patient data in order of patient number, from 1 to 52. *Baseline PASI for patient No. 11 was unavailable. BSA, body surface area; PASI, Psoriasis Area and Severity Index.
therapeutic effect was dose-dependent.10,11 Furthermore, several short-term trials (12-24 weeks) with open-label extensions were also able to demonstrate longer-term safety and efficacy of ETN in patients with PsO for up to 2.5 years.12,13 Lastly, results from OBSERVE-5, a 5-year observational registry, demonstrated that ETN efficacy, as measured by psoriasis-affected BSA improvement, static Physician’s Global Assessment (sPGA), and Dermatology Life Quality Index (DLQI) response, was sustained for up to 5 years.9 In this case series, improvements in PASI from baseline were maintained long-term, as these patients have currently
received treatment for up to 10 years or more. Percentage of affected BSA also showed sustained improvement from baseline in these patients.
PsO Patients Treated With ETN for 10 Years or More Currently, ETN safety and efficacy data in patients with PsO has only been reported for up to 5 years of therapy, despite there being patients who have been on ETN therapy for over 10 years. At the time of data collection, more than half of the
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Journal of Cutaneous Medicine and Surgery
Table 2. Therapy Prior to and During Etanercept Treatment. Treatments Prior to Starting ETN Patient No.
Topical Therapy
Phototherapy
Systemic Therapy
Current ETN Dose
Biologic Treatments
25 mg QW
50 mg QW
50 mg Q2W
50 mg BIW
Current Concomitant Therapy 100 mg QW
Topical Therapy
Phototherapy
Systemic Therapy
1
•
•
•
2
•
•
•
•
•
•a
3
•
4
•
5
•
•
•a
6
•
•
•a,c
•
d
•
a,c
7
•
• •
8
•
•
9
•
•
10
•
•
11
•
•
•
•b
• •e
•
•a,c,f,g
•b
•
a,d
b
•
•
•
•
•
•
•
13
•
•
•a
•h
14
•
•
•a
15
•
•
•a
16
•
•
•c,g
17
•
•
18
•
•
•
• •e
• •
•
•
•
•
• •a,g
• g
21
•
•
•
22
•
•
•a,g
23
•
•
24
•
•
25
•
•a,g
•
•
•a
•
•
•b
g
•
19 •
• •
12
20
•
•
•
•
•
•
26
•
•
•
27
•
•
•a,g
28
•
•g
•
•
a,g
•
g
•
29
• •b
•
30
•
•
•
31
•
•
•a
•
•a
•
33
•
a
•
•
34
•
•a,c
•
35
•
a
•
•
36
•
•a,d
•
i
•
32
37
•
•
38
•
•i
39
•
40
•
41
•
42
•
43
•
•
•i i
•
•i
•
•g
•
•
•
•
•i
•
•
•
•
•
•
(continued)
7
Bourcier et al Table 2. (continued) Treatments Prior to Starting ETN Patient No. 44
Topical Therapy
Phototherapy
Systemic Therapy
Biologic Treatments
Current ETN Dose 25 mg QW
50 mg QW
• i
45
•
•
46
•
•i
47
•
48
•
49
•
•
50
•
•
51
•
52
•
50 mg Q2W
50 mg BIW
Current Concomitant Therapy 100 mg QW
Phototherapy
Systemic Therapy
•
•
•
•
•
•
Topical Therapy
•
•
•
•
Abbreviations: BIW, twice weekly; ETN, etanercept; QW, weekly; Q2W, once every other week. a Methotrexate. b Alefacept. c Cyclosporine. d Voclosporin. e Efalizumab. f Mycophenolate mofetil. g Retinoid. h Infliximab. i Name of medication not specified.
cases had been receiving ETN treatment for 10 years or more. PASI scores and percentage of affected BSA showed sustained improvement in all of these patients, with an average PASI score and percentage of affected BSA of 1.7 and 1.4% at data collection, respectively.
Prior and Concomitant PsO Treatments PsO therapy ranges from topical treatment for patients with mild disease to systemic, targeted, or phototherapy for patients with moderate to severe disease. Table 2 lists the treatments used by the 52 patients described in this report prior to starting ETN therapy and the current treatments used concomitantly with ETN. In general, topical therapies are used in patients with localized PsO, with topical corticosteroid therapy being the most common and convenient treatment.5 Alternatives to topical corticosteroids are vitamin D analogs, including calcipotriene, calcitriol, and tacalcitol. In many cases, topical therapies are used concomitantly in patients who are undergoing systemic, targeted, or phototherapy.5 In this case series, 46 of 52 (88.4%) patients received topical therapy prior to receiving ETN, while at data collection, 13 of 52 (25%) patients received topical therapy concurrently with ETN treatment. Phototherapy is a treatment option for patients with PsO that is refractory to topical agents or too widespread to treat with topical therapy. Broadband UVB (BBUVB) phototherapy, narrowband UVB (NBUVB), and PUVA photochemotherapy can be used on select patients. Prior to initiating ETN treatment, 28 of 52 (53.8%) patients received phototherapy. At the time of
data collection, 2 patients (Nos. 16 and 38) received phototherapy in addition to ETN, while patient No. 16 also received additional topical therapy. Another alternative to topical therapy in the case of refractoriness and/or widespread PsO or lack of response to phototherapy is systemic therapy. Traditional systemic therapy agents include methotrexate (MTX), retinoids, and cyclosporine. These medications have potential toxicities that may limit their use. In this case series, prior to starting ETN, 34 of 52 (65.3%) patients received systemic therapy. At data collection, 2 patients (Nos. 4 and 19) received MTX in addition to ETN. Patient No. 32 also received a retinoid, and patient Nos. 4 and 32 also received topical therapy. Combining phototherapy with ETN is an effective treatment option that can accelerate the clearance of psoriatic lesions in ETN-treated patients with PsO.14-17 Two patients used phototherapy concomitantly with ETN at the start of therapy and up until data collection. Combination therapy involving ETN with MTX has also shown good efficacy in PsO patients.18 Two patients in this report were treated with ETN and MTX (Nos. 4 and 19). One patient (No. 32) was treated with ETN and a retinoid in addition to a topical therapy, though no patients received cyclosporine in combination with ETN.
PsA PsA is a seronegative arthritis that affects up to 30% of patients with plaque PsO19; however, the risk of developing PsA appears to be associated with the extent of skin PsO.20 The safety and efficacy of ETN for the treatment of PsA has
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Journal of Cutaneous Medicine and Surgery
Table 3. PsO Patients on Etanercept Over 10 Years.a Duration PsO of ETN Patient No. Age (y) Sex Duration (y) Therapy (y) 1 2 4 5 6 7 8 10 12 17 18 19 20 21 25 26 27 28 29 30 31 34 35 37 40 42 43 44 48 49 50 51 52
64 63 64 57 49 53 82 48 43 54 47 67 38 61 56 81 63 38 55 70 52 53 67 49 62 67 71 50 46 70 69 65 40
M M M M F M F M M M M F F M F M M M F M M M M M M M M F M M M M M
24 33 35 35 44 29 20 29 28 29 22 61 23 27 44 72 39 23 34 38 30 43 38 30 14 30 51 25 25 37 14 27 18
10 11 10 11 11 11 10 11 12 10 11 11 11 10 10 10 11 11 11 10 10 10 10 12 10 11 11 11 12 10 12 12 11
Baseline Dose
Current Dose
50 mg BIW 50 mg BIW 50 mg BIW 25 mg BIW 25 mg BIW 25 mg BIW 50 mg BIW 25 mg BIW 50 mg BIW 50 mg BIW 25 mg BIW 25 mg BIW 25 mg BIW 25 mg BIW 50 mg BIW 50 mg BIW 25 mg BIW 50 mg BIW 25 mg BIW 50 mg BIW 50 mg BIW 50 mg BIW 50 mg BIW
50 mg BIW 50 mg BIW 50 mg BIW 50 mg QW 50 mg QW 50 mg Q2W 50 mg QW 50 mg BIW 50 mg QW 50 mg QW 50 mg BIW 50 mg QW 50 mg QW 25 mg QW 50 mg QW 50 mg QW 50 mg BIW 50 mg QW 50 mg QW 50 mg QW 50 mg BIW 50 mg QW 50 mg QW 50 mg QW 100 mg QW 50 mg QW 100 mg QW 100 mg QW 100 mg QW 50 mg QW 100 mg QW 100 mg QW 50 mg QW
b b b b b b b b b b
Baseline Current Baseline Current PsA BSA (%) BSA (%) PASI PASI Duration (y) 10 11 13 50 23 22 15 12 40 13 36 18 28 15 14 34 45 26 12 11 68 20 15 15 21 19 16 15 11 30 22 28 31
0.7 0.2 0.5 1 0 3 4 0 0.4 0 2.5 0.5 4 1 1 1 3 1.5 0 2.5 5 1 2 2 1 0.1 0.2 1 0.5 0.1 2 0.2 1
16.4 14.4 13.2 29.2 26.5 18 15.7 15 28.2 13.2 26.5 11.4 16.9 15.4 12.8 23.4 22.3 25.2 12.2 16.6 39.8 15 18 22 38 26 18 23 16 35 27 35 27
1.8 0.6 0.6 1.6 0 6 3 0 1.2 0 4.2 0.5 5.2 2 1.8 3.2 3.2 1.8 0 2 3.2 1.2 1.8 2 0.6 0.4 1.3 1.4 1.1 2.3 1.8 0.7 0.5
N/A N/A 0.08 23 N/A N/A 20 N/A N/A 18 N/A 27 19 20 N/A N/A 26 16 13 20 29 b b
N/A N/A N/A 25 15 16 38 N/A N/A 8
Abbreviations: BIW, twice weekly; BSA, body surface area; ETN, etanercept; F, female; M, male; N/A, not applicable; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsO, psoriasis; QW, once weekly; Q2W, once every other week. a All patients were Caucasian. b Data unknown.
been demonstrated in several short-term (≤24 weeks) studies and an open-label extension study that followed patients up to 2 years.21,22 In this case series, 46.2% (24/52) of patients developed PsA. With the exception of 2 patients, PsA diagnosis preceded ETN therapy. In Canada, ETN is approved for the treatment of PsA with a starting dose of 50 mg QW, which is the dose received by most of the patients with PsA in this case series (13/24; 54.2%).
Conclusion The clinical experience described in this descriptive case series suggests maintenance of ETN efficacy in patients
with PsO receiving therapy for 7 years or more and indicates that patients can be successfully managed with longterm ETN therapy. Furthermore, this long-term efficacy was also demonstrated in patients with PsA. Further study of a greater number of PsO patients receiving long-term (≥7 years) ETN treatment may be able to more completely illuminate efficacy and safety of ETN in this patient population. Acknowledgments We thank Jessica Benzaquen, MSc, and Julia Swiercz, PhD, from Synapse Medical Communications, Oakville, Ontario, who provided medical writing assistance in the form of drafting
Bourcier et al and revising as per authors’ directions and in accordance with the standards set out by the International Committee of Medical Journal Editors.
Authors’ Note Amgen Canada Inc oversaw the design, conduct, and collection of data in the manuscript and assisted in the analysis and interpretation of data.
Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Marc Bourcier received honorariums for advisory boards and grants for clinical trials: AbbVie, Actelion, Amgen, Astellas, Novartis, Leo, Janssen, Merck, and Pfizer. Kim Papp is a consultant, on advisory boards, participates in speaker’s bureaus, and is an investigator for Amgen. Wayne Gulliver received honoraria for consultant services from Amgen. Yves Poulin received honoraria for lectures and/or research grants from Abbvie, Actelion, Amgen, Boehringer, Celgene, Eli-Lilly, Galderma, Incyte, Janssen, LeoPharma, Merck, Novartis, Pfizer, Schering, and Takeda. Kirk Barber received honoraria for consultant services from Amgen. Melanie Poulin-Costello and Jennifer Shelton are employees of Amgen Canada.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This manuscript was supported in part by Amgen Canada Inc.
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