Journal of Dermatology and Clinical Research

Cite this article: Koc E, Solak N, Balcı DD, Engin B, Atakan N, et al. (2017) An Observational Study to Evaluate Efficacy and Safety of Anti-TNF Agents in Patients with Moderate to Severe Psoriasis. J Dermatolog Clin Res 5(2): 1098.

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*Corresponding authorErol Koc, Faculty of Medicine, Bahcesehir University, Ankara, Turkey; Tel: 90 312 666 81 54; Fax: 90 312 666 86 66; Email:

Submitted: 07 June 2016

Accepted: 30 March 2017

Published: 31 March 2017

Copyright© 2017 Koc et al.

OPEN ACCESS

Keywords•Psoriasis treatment•TNF•Quality of Life

Research Article

An Observational Study to Evaluate Efficacy and Safety of Anti-TNF Agents in Patients with Moderate to Severe PsoriasisErol Koc1*, Nilgun Solak2, Didem Didar Balcı3, Burhan Engin4, Nilgun Atakan5, Serap Ozturkcan6, Fatma Aydin7, Mustafa Ozdemir8, Ozer Arican9, Emel Bulbul Baskan10, Mehmet Ali Gurer11, Sedat Ozcelik12, Neslihan Sendur13, Mukadder Kocak14, and Hamdi Ozcan15

1Faculty of Medicine, Bahcesehir University, Turkey 2Faculty of Medicine, Bulent Ecevit University,Turkey 3Faculty of Medicine, İzmir Tepecik Training and Research Hospital, Turkey 4Istanbul Bilim University, Cerrahpasa School of Medicine, Turkey 5Faculty of Medicine, Hacettepe University, Turkey 6Faculty of Medicine, Celal Bayar University, Turkey 7Faculty of Medicine, Ondokuz Mayis University, Turkey 8Faculty of Medicine, Medipol University, Turkey 9Medical Faculty, Istanbul Medicana Hospital, Retired Professor, Edirne Trakya University, Turkey 10Faculty of Medicine, Uludag University, Turkey 11Faculty of Medicine, Gazi University, Turkey 12Faculty of Medicine, Cumhuriyet University, Turkey 13Faculty of Medicine, Adnan Menderes University, Turkey 14Faculty of Medicine, Ankara Koru Hospital, Turkey 15Faculty of Medicine, Arion Esthetic, Turkey

Abstract

Background: With the introduction of novel therapeutics, evaluation of efficacy becomes critical to prioritize therapeutic potential and minimize patient risk in psoriasis.

Methods: A total of 86 patients with moderate to severe psoriasis receiving anti- tumor necrosis factor (TNF) treatment were included in a 24-week, national, multi-center, observational study to evaluate efficacy and safety of anti- TNF agents. Efficacy was evaluated via psoriasis area and severity index (PASI) and static/dynamic photographic physician psoriasis global assessment (PGA). Patient-reported outcomes for dynamic photographic scale, dermatology life quality index (DLQI), and work productivity and activity impairment questionnaire-psoriasis (WPAI-PSO) were also recorded.

Results: Median (interquartile range) psoriasis area and severity index score significantly decreased from 20 (15) to 2 (5); and 70.9% of the patients had a ≥ 75% reduction in at week 24 (p <0.05). Baseline median (interquartile range) DLQI score has decreased from 16 (10) to 1.5 (7) at week 24 (p <0.001), with no or minimal impact on patients’ lives in 72.1% of the patients. PASI reduction was significantly correlated to DLQI reduction and reductions in presentee-ism, WPAI-PSO. Clear or almost clear psoriatic lesions were reported in 60.5% of patients and dynamic PGA revealed median alteration in psoriasis severity to be 1.5 (3) at week 24. Adverse events were noted in 17.4% of the patients and most were mild or moderate (57.7%).

Conclusions: Our findings presenting reduction in disease severity, disappearance of psoriatic lesions, and improvement in DLQI and WPAI-PSO indicate 24-week anti-TNF therapy to be safe and effective in the control of moderate to severe psoriasis.

ABBREVIATIONSTNF: Anti-tumor Necrosis Factor; PASI: Psoriasis Area

and Severity Index; PGA: Psoriasis Global Assessment; DLQI: Dermatology Life Quality Index; WPAI-PSO: Work Productivity and Activity Impairment Questionnaire-Psoriasis; BSA: Body Surface Area; HRQoL: Health-Related Quality of Life; SPSS: Statistical Package for the Social Sciences; SD: Standard

Deviation; IQR: Interquartile Range; AE: Adverse Event; ALT: Alanine Transaminase; AST: Aspartate Transaminase.

INTRODUCTIONWith a prevalence of 2% to 3% in the general population,

psoriasis is one of the most common immune-mediated disorders [1]. Psoriasis follows a relapsing and remitting course and is a lifelong disease with a major impact on affected patients’ physical

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and mental health [2,3], as well as their social life in relation to its early onset and chronic relapsing nature [4,5].

The range of treatment options for managing psoriasis has expanded since 2003 with the approval of biologic therapies, which have a good benefit-risk profile overall and are effective in patients who have not received adequate benefit with non-biologic systemic therapies [6,7]. The prospect of greater improvements in a patient’s quality of life, along with fewer adverse effects compared with traditional systemic therapies, has brought much attention to the use of biologic therapies in the treatment of psoriasis [8].

There are currently two approved groups of biologic agents that target tumor necrosis factor (TNF): anti-TNF monoclonal antibodies (adalimumab and infliximab), and soluble TNF receptors (etanercept). Efficacy has been well-established in clinical trials for etanercept [9-12], infliximab [13-15], and adalimumab [16,17] as well as the capacity of these agents to improve health-related quality of life [10,13,14,18-22].

Evaluation of efficacy is critical for novel therapeutics to prioritize therapeutic potential and minimize patient risk [23]. While numerous psoriasis severity tools have been investigated in several studies, no best instrument has yet been identified [24]. Psoriasis Area and Severity Index (PASI) is the most widely used measure [4]. Psoriasis Global Assessment (PGA) of disease severity and body surface area (BSA) are the other frequently used measures to quantify disease severity in psoriasis [4]. One of the most commonly used outcome parameters to assess the impact of the disease on quality of life is the dermatology life quality index (DLQI) [25], which is a widely used scale that has been translated into various languages.

In addition to the feelings of embarrassment, stigmatization, depression, and problems with self-esteem and body image that are common in patients with psoriasis, the disease has psychosocial effects that seriously affect patients’ lives and social relationships [2]. The psychosocial impact of the disease has been indicated by several studies in the past decade [2], with considerable heterogeneity of the clinical expression of the disease and the varying response to therapies [26]. This indicates the need for national studies to answer country-specific questions regarding the management of the disease as well as psychosocial impact and physical impairment associated with the disease.

Therefore, based on the lack of data concerning the epidemiology and psychosocial impact of psoriasis in Turkey, we have conducted an observational study to investigate the clinical success of biologic therapies in the treatment of psoriasis, as well as improvements in quality of life and work productivity.

MATERIALS AND METHODS

Study population

Male or female patients with moderate to severe psoriasis aged ≥ 18 and received treatment with anti-TNF agents and completed the study follow-up visits were included in this 24-week national, multi-center, observational, prospective photographic atlas study conducted in 25 dermatology clinics across Turkey. Female subjects who were pregnant, nursing, or of

childbearing potential but refused to use a medically acceptable form of contraception throughout the study were excluded, as were patients with untreated tuberculosis.

The written informed consent to participate in the study was obtained from each subject following a detailed explanation of the study. The protocol of the study was approved by the institutional ethics committee.

Data collection

All patients were evaluated in 5 consecutive visits performed at week 0 (baseline visit), week 4 (visit 2), week 8 (visit 3), week 16 (visit 4), and week 24 (visit 5). Patient demographics, medical background, and clinical features related to psoriasis data were collected at the baseline visit. PASI, DLQI, photographic dynamic/static physician PGA, photographic dynamic patient PGA evaluations, and adverse events (AEs) were collected at each visit; Work Productivity and Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) was evaluated at baseline and the final visit of the study. PASI, DLQI and WPAI scores were also evaluated with respect to type of anti-TNF agent used, while univariate and multivariate linear regression analyses were performed to identify factors predicting WPAI score reduction.

Psoriasis area and severity index

Psoriasis was classified as mild, moderate, or severe based on the severity of cutaneous manifestations rated using 3 PASI criteria: redness, thickness, and scaliness. PASI is the most widely used composite score, assessing both the extent of body surface area involvement and the severity of the psoriatic lesions by location via a continuous score, ranging from 0 to 72, in which a larger number indicates greater psoriasis severity.

Dermatology life quality index

The DLQI, which is a questionnaire that assesses symptoms, feelings, and limitations that the disease poses on patients’ daily activities, was used to assess the impact of psoriasis on health-related quality of life (HRQoL). The DLQI score ranges from 0 to 30; a lower score denotes a better quality of life and values higher than 10 indicate very severe impairment on quality of life [6,27]. Psoriasis is considered moderate to severe if the patient’s PASI score and DLQI score are 10 or greater [26,28].

Work productivity and activity impairment questionnaire-psoriasis

The scores for WPAI-PSO were evaluated for absenteeism (percentage of time missed from work as a result of the disease), presenteeism (percentage of reduced productivity while working), activity impairment (percentage of impairment in regular daily activities), and work productivity loss (percentage of work impairment associated with psoriasis from both absenteeism and presenteeism) [28].

Psoriasis global assessment

A standardized set of photographs were taken at the beginning of the study and at weeks 4, 8, 16, and 24 by a trained dermatologist. A set of nine standardized poses were taken at

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each visit [27]. All photographs collected from each site were transferred to the coordinator center of the study, evaluated and scored by the same investigator group.

The main outcome measure was the global assessment of the changes between the different sets of photographs taken at weeks 0, 4, 8, 16, and 24. The photograph sets for each patient were assessed by comparing them with baseline photographs to evaluate the change by using the photographic dynamic PGA scale and current severity by using photographic static PGA.

Evaluation of the single-point severity of psoriasis via static PGA by physicians

Psoriasis severity was rated by using static PGA for each patient at each time point from 0 (no lesion) to 6 (severe psoriasis).

Evaluation of the change in psoriasis severity via dynamic PGA by physicians and patients

The change in psoriasis severity was rated from –5 (considerable deterioration) to +5 (considerable improvement), for each patient, using dynamic PGA; zero means “no or minimal change (–10 to +10%).” The change of the severity of psoriasis was also assessed for each patient by evaluating their photographs using the dynamic photographic scale adapted to the visual analog scale, ranging from –5 to +5.

Statistical analysis

Statistical analysis was conducted using the SPSS (version 13.0, SPSS Inc. Chicago, IL, USA) software. The Wilcoxon signed-rank test was used for the comparative analysis of photographic PGA scores, PASI, and DLQI scores obtained at 5 consecutive visits throughout the study period. As a part of univariate analysis; continuous variables were evaluated by univariate linear regression whereas categorical ones with non-parametric comparison tests. Mann-Whitney U test was used due to non-normal distribution patterns. If a variable has significant effect on score in univariate, it is included to multivariate analysis. Best multivariate model was selected best (Bayesian Information Criteria (BIC) value. Data were expressed as “mean (standard deviation; SD),” “median (interquartile range; IQR),” minimum-maximum, and percentage where appropriate. P <0.05 was considered statistically significant.

RESULTS AND DISCUSSION

Basic demographic and clinical features

A total of 86 patients (38.4% female) with a mean (SD) age of 42.8 (13.5) years, body mass index 29.5 (16.2) kg/m2, and psoriasis for 16.4 (8.7) years were included in the study. The percentage of patients who were dyslipidemic, hypertensive, and hypoglycemic were 18.6% (16/86), 17.4% (15/86), and 17.4% (15/86), respectively. Unemployment was identified in 59.3% of the patients at baseline and 60.5% at week 24. The anti-TNF agents adalimumab (starting dose of median 80.0 mg/week), infliximab (starting dose median 5.0 mg/kg), and etanercept (starting dose median 100.0 mg/week) were administered to 45 (52.0%), 23 (27.0%), and 18 (21.0%) patients, respectively.

PASI scores

Baseline median (IQR) PASI score was 20.0 (15.0); it decreased to 2.0 (5.3), an approximately 90% reduction between weeks 16 and 24 (p <0.001 vs. baseline; Table 1). A ≥ 75% reduction in PASI (PASI 75) was noted in 70.9% of patients at week 24; a ≥ 90% reduction (PASI 90) was noted in 51.2% of patients at week 24 (Table 1).

DLQI scores

Median (IQR) DLQI score also rapidly decreased from 16 (10) at baseline to 1.5 (7) at week 24, with a reduction of 90.5% (p <0.001 vs. baseline; (Table 2). Psoriasis was identified to have no or minimal impact on patients’ lives (DLQI score 0–5) in 9.3% of patients at baseline and 72.1% of patients at week 24 (Table 2).

WPAI scores

When compared to baseline values, there was a significant reduction in median (IQR) ratios for absenteeism (11 [50] vs 0 [0]), activity impairment (45 [60] vs 5 [30]), presenteeism (45 [40] vs 0 [30]), and work productivity loss (57 [57] vs 0 [20]) components of the WPAI scores at week 24 (p <0.001 for each; (Table 3)).

PASI, DLQI and WPAI scores with respect to type of anti-TNF agent

No significant difference was noted between adalimumab, etanercept and infliximab treatments in terms of PASI and DLQI scores as well as % reduction from baseline PASI and DLQI scores. Other than significantly higher scores for absenteeism with adalimumab than other agents, no significant difference was noted between treatment agents in terms of WPAI scores (Table 4).

Correlations between reductions in PASI, DLQI, and WPAI scores at week 24

There was a significant positive correlation between PASI score reduction and DLQI score reduction (r=0.591; p<0.001) and reductions in all components of WPAI, except absenteeism, at week 24. Reductions in the components of the WPAI did not correlate with DLQI reductions (Table 5).

Linear regression analyses for determinants of WPAI score reduction

Univariate analysis revealed higher WPAI score reduction to be associated with baseline PASI scores (p=0.013) and PASI reduction obtained at 24th week (p <0.01) for activity impairment, and with DLQI reduction obtained at 24th week for presenteeism (p=0.048), work productivity loss (p=0.040) and activity impairment (p <0.001) domains. Older age at disease onset was associated with lesser reduction in work productivity loss (p=0.036) and presenteeism (p=0.049) scores, while older age of patients was associated with lesser reduction in work productivity loss scores (p=0.037) (Table 6).

Multivariate analysis revealed that DLQI reduction obtained at 24th week was a significant determinant of better reduction in WPAI scores including presenteeism (B, 0.41, %95 CI 0.02-0.81, p=0.041), work productivity loss (B, 0.48, %95 CI 0.011-

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PASI scoresa PASI 90 PASI 75 PASI 50Absolute score % Reduction

% of patientsMedian (IQR)

Baseline 20.0 (15.0) - - - -

Week 4 6.8 (10.6)b 54.7 (55.6) 8.1 31.4 55.8

Week 8 3.8 (8.4)b,c 76.2 (46.0)c 33.7 52.3 73.3

Week 16 2.0 (5.3)b,c,d 88.2 (31.2)c,f 46.5 66.3 88.4

Week 24 1.9 (4.5)b,c,e 90.3 (30.0)c,e 51.2 70.9 87.2IQR: interquartile range.aOverall p<0.001 (Friedman test).bp<0.001 compared to baseline (Wilcoxon test).cp<0.001 compared to week 4 (Wilcoxon test).dp=0.002; ep=0.003 and fp=0.001 compared to week 8 (Wilcoxon test).

Table 2: Dermatology Life Quality Index (DLQI) scores at baseline and study visits (n=86).Baseline Week 4 Week 8 Week 16 Week 24

Median (IQR)Absolute DLQI scores 16.0 (10.0) 5.0 (10.0)a 2.0 (9.0)a,b 1.0 (4.0)a,b 1.5 (7.0)a,c

% Reduction in DLQI scores - 61.8 (48.6) 80.6 (50.0)b 91.8 (37.5)b 90.5 (43.8)d

Effect of disease on patients’ lives n (%)

0–1 = no effect at all 2 (2.3) 23 (26.7) 37 (43.0) 50 (58.1) 43 (50.0)

2–5 = small effect 6 (7.0) 23 (26.7) 19 (22.1) 15 (17.4) 19 (22.1)

6–10 = moderate effect 14 (16.3) 18 (20.9) 15 (17.4) 9 (10.5) 10 (11.6)

11–20 = very large effect 43 (50.0) 19 (22.1) 15 (17.4) 9 (10.5) 11 (12.8)

21–30 = extremely large effect 21 (24.4) 3 (3.5) 0 (0.0) 3 (3.5) 3 (3.5)IQR: interquartile range.ap<0.001 compared to baseline (Wilcoxon test).bp<0.001; cp=0.0019 and dp=0.0023 compared to week 4 (Wilcoxon test).

Table 3: Work Productivity and Activity Impairment (WPAI) scores at baseline and week 24 of patients who were working actively during the study period (n=30).

WPAI scores*Absolute (%) % Reduction

Median (IQR)

Absenteeism (n=29)Baseline 11 (50)

100 (100)Week 24 0 (0)a

Activity impairment (n=30)Baseline 45 (60)

62.5 (100)Week 24 5 (30)a

Presenteeism (n=30)Baseline 45 (40)

75.7 (100)Week 24 0 (30)a

Work productivity loss (n=29)Baseline 57 (57)

84.8 (100)Week 24 0 (20)a

IQR: interquartile range.ap≤0.001 compared to baseline (Wilcoxon test).

0.85, p=0.013), p=0.040) and activity impairment (B, 0.46, %95 CI 0.18-0.74, p=0.001), while older age at disease onset was a significant determinant lesser reduction in presenteeism scores (B,-0.02, %95 CI -0.04- -0.001, p=0.042) (Table 6).

Static and dynamic photographic PGA

Both physician and patient PGA revealed significant improvement upon treatment; however, the amount of decrease was not consistent with time. Static physician PGA severity

scores decreased from 5 (2) to 1 (1) at week 24 (p <0.001; Table 7). Investigators reported no or almost cleared psoriatic lesion in 0.0% of patients at baseline and 60.5% of patient at week 24.

Safety results

A total of 18 patients (20.9%) experienced 26 AEs, of which only 3 toxic hepatitis with a probable causality relationship with the study drug, gangrenous emphysema (causality was not reported), and catheter infection plus infected endocarditis that

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Table 4: PASI, DLQI and WPAI scores with respect to type of anti-TNF agent.

Anti-TNF agent

Mean (95% CI) Adalimumab (n=45) Etanercept (n=18) Infliximab (n=23)

PASI scores

Baseline 21.8 (18.3-25.2) 20.5 (15-25.9) 21.1 (16.3-26.0)Week 4 10.0 (7.4-12.6) 13.2 (9.0-17.4) 7.9 (4.2-11.6)Week 8 8.1 (5.2-10.9) 7.7 (3.2-12.2) 4.4 (0.4-8.3)

Week 16 4.6 (2.7-6.6) 6.5 (3.4-9.6) 3.0 (0.3-5.8)Week 24 3.5 (2.0-5.0) 5.6 (3.3-8.0) 3.2 (1.2-5.3)p value1 0.365

% reduction from baseline PASI score

Week 4 53.5 (43.1-64.0) 36.6 (20.0-53.1) 52.7 (38.1-67.3)Week 8 65.5 (54.9-76.1) 62.5 (45.7-79.3) 69.7 (54.9-84.6)

Week 16 77.5 (66.7-88.3) 69.3 (52.2-86.3) 78.9 (63.8-94.0)Week 24 84.2 (76.7-91.7) 73.2 (61.3-85.1) 75.1 (64.6-85.6)p value1 0.422

DLQI Score

Baseline 16.0 (13.9-18.1) 14.3 (10.9-17.7) 15.1 (12.1-18.1)Week 4 6.8 (5.0-8.6) 7.7 (4.9-10.5) 5.0 (2.5-7.4)Week 8 4.3 (2.7-5.9) 5.2 (2.7-7.7) 4.6 (2.4-6.8)

Week 16 3.8 (1.8-5.8) 6.2 (3.0-9.3) 3.0 (0.2-5.8)Week 24 3.3 (1.3-5.3) 6.4 (3.3-9.5) 6.0 (3.2-8.8)p value1 0.650

% reduction from baseline DLQI score

Week 4 53.8 (41.1-66.5) 39.0 (18.9-59.1) 65.4 (47.7-83.2)Week 8 68.6 (56.8-80.3) 58.9 (40.4-77.5) 69.2 (52.8-85.7)

Week 16 75.7 (64.5-86.8) 61.0 (43.4-78.6) 81.7 (66.1-97.3)Week 24 73.7 (58.1-89.2) 61.4 (36.8-86) 52.9 (31.1-74.6)p value1 0.366

Adalimumab (n=45) Etanercept (n=18) Infliximab (n=23)

WPAI scores n Median (IQR) n Median (IQR) n Median (IQR)

Absenteeism 21 100(100.0) 5 0 (0.0) 7 0.0(100.0)

p value2 0.023

Activity impairment 45 75.0(66.7) 18 71.3(100.0) 23 80.0(100.0)

p value2 0.981

Presenteeism 22 75.7(875) 5 100.0(100.0) 8 91.7(100.0)

p value2 0.976

Work productivity loss 21 89.2(87.5) 5 100.0(100.0) 7 100.0(100.0)

p value2 0.938

PASI: Psoriasis Area and Severity Index; DLQI: Dermatology Life Quality Index; WPAI: Work Productivity and Activity Impairment; TNF:Tumor necrosis factor; IQR: interquartile range1Repeated measures variance analysis, 2Kruskal Wallis

Table 5: Correlations between reductions in PASI, DLQI, and WPAI scores at week 24.

Score reductions (%) at week 24 DLQI reduction (%) at week 24 PASI reduction (%) at week 24

WPAI absenteeism reduction (n=29)Rho 0.126 0.153

P 0.516 0.427

WPAI presenteeism reduction (n=30)Rho 0.322 0.547

P 0.083 0.002

WPAI work productivity loss reduction (n=29)Rho 0.330 0.420

P 0.080 0.023

WPAI activity impairment reduction (n=30)Rho 0.303 0.481

P 0.104 0.007

PASI (n=86)Rho 0.591 --

P <0.001 --

DLQI: Dermatology Life Quality Index; PASI: Psoriasis Area and Severity Index; WPAI: Work Productivity and Activity Impairment.

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was considered not related to the study drug) were serious and caused discontinuation of the anti-TNF treatment. More than half of the AEs (57.7%) were mild or moderate in severity; one-third (34.6%) were not suspected to be related to anti-TNF agent treatment and no action was taken for 57.7% of the AEs (Table 8).

Observed AEs were as follows: general disorders and administration site conditions (n=9; injection-site reaction [7], fatigue [2]); skin and subcutaneous tissue disorders (n=7; pruritus [3], alopecia [2], erythema multiforme [1], and ingrown nail [1]); respiratory, thoracic, and mediastinal disorders (n=5; cough [2], dyspnea [2], flu-like symptoms [1]); investigations (n=5; hepatic enzyme increased [ALT {2}, AST {2}] and weight increased [1]); musculoskeletal and connective tissue disorders (exostosis; n=1), and gastrointestinal disorders (abdominal distension; n=1).

DISCUSSIONOur results concerning the evaluation of effectiveness and

safety of anti-TNF agents in patients with moderate to severe psoriasis revealed significant reduction in psoriasis severity based on PASI and static/dynamic PGA scores, significant decrease on the impact of the disease on patients’ lives, as well as

in the impairment of work productivity and activity, regardless of the type of anti-TNF agent prescribed. DLQI reduction at 24th week predicted better reduction in WPAI scores including presenteeism, work productivity loss and activity impairment, while older age at disease onset was a significant determinant of lesser reduction in presenteeism scores. Anti-TNF drugs’ efficacies had been shown in placebo-controlled trials of patients with moderate to severe plaque psoriasis. Few therapies have demonstrated efficacy of TNFs versus methotrexate under controlled conditions [16,29]; however, the effectiveness of these drugs has not been investigated in a local real-life setting. Although randomized, controlled trials are the gold standard for evaluating treatments, strict inclusion/exclusion criteria in such trials often limit the range of patients studied and can call into question the generalizability of the results. In observational studies, inclusion/exclusion criteria are greatly reduced and the patients enrolled are highly representative of those seen in routine clinical practice. As with any observational study, these patients were not randomized to a treatment arm; clinicians assigned a treatment using their best clinical judgment.

PASI 75 response has been proposed as the ideal treatment goal that is both practical and realistic, although complete clearance of skin lesions may be regarded as the ultimate treatment goal

Table 6: Univariate analysis for factors associated with WPAI score reduction.

Univariate analysis

WPAI score reductionAbsenteeism Presenteeism Work productivity loss Activity impairment

B (95%CI) P B (95%CI) P B (95%CI) P B (95%CI) PPASI reduction (%) at week 24

0.24 (-0.78 / 1.26) 0.632 0.55 (-0.26 / 1.36) 0.174 0.51 (-0.22 / 1.24) 0.166 1.05 (0.57 / 1.53) <0.001

PASI at baseline -0.01 (-0.03 / 0.02) 0.588 0.001 (-0.02 / 0.02) 0.957 -0.01 (-0.02 / 0.01) 0.565 0.01 (0.003 / 0.03) 0.013

DLQI reduction (%) at week 24

0.16 (-0.42 / 0.74) 0.570 0.42 (0.004 / 0.83) 0.048 0.42 (0.02 / 0.82) 0.040 0.61 (0.38 / 0.83) <0.001

Age (year) -0.01 (-0.03 / 0.01) 0.333 -0.01 (-0.02 / 0.01) 0.344 -0.02 (-0.03 /

-0.001) 0.037 -0.001 (-0.01 / 0.01) 0.859

Age at disease onset (year)

-0.02 (-0.04 / 0.01) 0.159 -0.02 (-0.04 / -0.0001) 0.049 -0.02 (-0.04 /

-0.001) 0.036 -0.01 (-0.02 / 0.005) 0.308

Gender ( male) NA 0.541* NA 0.190* NA 0.953* NA 0.688*Disease duration

(year)0.004 (-0.03 /

0.03) 0.776 0.01 (-0.01 / 0.03) 0.339 -0.01 (-0.03 / 0.02) 0.644 0.01 (-0.01 / 0.03) 0.190

Having dyslipidaemia NA 0.469* NA 0.543* NA 0.597* NA 0.224*

Having hypertension NA 0.297* NA 0.449* NA 0.946* NA 0.558*

Having hypoglycaemia NA 0.738* NA 0.107* NA 0.083* NA 0.689*

Multivariate linear regression analysisWPAI score reduction

Presenteeism Work productivity loss Activity impairmentB (95%CI) P B (95%CI) P B (95%CI) P

PASI reduction (%) at week 24 NIM - NIM - 0.38 (-0.19 / 0.95) 0.192PASI at baseline NIM - NIM - 0.01 (<0.01 / 0.02) 0.048

DLQI reduction (%) at week 24 0.41 (0.02 / 0.81) 0.041 0.48 (0.11 / 0.85) 0.013 0.46 (0.18 / 0.74) 0.001Age (year) NIM - -0.01 (-0.03 / 0.01) 0.213 NIM -

Age at disease onset (year) -0.02 (-0.04 / -0.001) 0.042 -0.01 (-0.03 / 0.01) 0.417 NIM -

95%CI: lower and upper boundaries of 95% confidence interval of liner regression coefficient, B: liner regression coefficient, N: patient count, NA: not applicable, NIM: not included to multivariate model. * p value of Mann Whitney U test

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Table 7: Static and dynamic photographic Psoriasis Global Assessment (PGA) score (n=86).

Baseline Week 4 Week 8 Week 16 Week 24

Dynamic photographic PGA* Median (IQR)

By physiciana 0 (0) 3 (2)b 3 (2)b 2 (4)b 1.5 (3)b,c

By patienta 0 (0) 3 (2)b 3 (2)b 2 (4)b 1.5 (4)b,c

Static photographic PGA**

Absolute scorea 5 (2) 3 (2)b 2 (2)b,c 1 (1)b,c 1 (1)b,c

Classification n (%)

Clear (no lesion) 0 (0.0) 0 (0.0) 11 (12.8) 13 (15.1) 14 (16.3)

Psoriasis almost cleared 0 (0.0) 17 (19.8) 30 (34.9) 35 (40.7) 38 (44.2)

Mild psoriasis 0 (0.0) 24 (27.9) 17 (19.8) 18 (20.9) 19 (22.1)

Mild to moderate psoriasis 1 (1.2) 11 (12.8) 11 (12.8) 8 (9.3) 4 (4.7)

Moderate psoriasis 35 (40.7) 25 (29.1) 10 (11.6) 8 (9.3) 8 (9.3)

Moderate to severe psoriasis 27 (31.4) 3 (3.5) 3 (3.5) 2 (2.3) 3 (3.5)

Severe psoriasis 23 (26.7) 6 (7.0) 4 (4.7) 2 (2.3) 0 (0.0)*0: no or minimal change (–10 to +10%); 1: mild improvement (+10 to + 29%); 2: moderate improvement (+ 30 to + 49%); 3: moderate to large improvement (+50 to + 69%).**6 (severe psoriasis) to 0 (no lesion).aOverall p<0.001 (Friedman test).bp<0.001 compared to baseline (Wilcoxon test).cp<0.001 compared to week 4 (Wilcoxon test).

Table 8: Adverse events (n=29) in relation to severity, causal relationship to medication and action taken.

Severity n (%)

Mild 7 (24.1)

Moderate 8 (27.6)

Severe 14 (48.3)

Casual relationship to the drug

Not related 10 (34.5)

Possibly related 6 (20.7)

Probably related 11 (37.9)

Not reported 2 (6.9)

Action taken

Discontinued study drug 5 (17.2)

None 15 (51.7)

Additional treatment 6 (20.7)

Not reported 3 (10.3)

for psoriasis [26,30]. Accordingly, the identification of ≥ 75% reduction in PASI scores in 31.4%, 52.3%, 66.3%, and 70.9% of the patients at consecutive visits from week 4 to week 24, as well as the increase in the percentage of the patients with a ≥ 90% reduction in PASI scores from 8.1% at week 4 to 51.2% at week 24, supports that most of the patients with moderate to severe psoriasis achieve satisfactory disease control in the short term with at least one of the systemic agents currently available [5,31]. Our findings related to the reduction in the severity of psoriasis at each visit compared with baseline during the entire course of follow up via both PASI and PGA scores is in line with the results of a recent systemic meta-analysis that indicates the 2 methods correlate with a few points of divergence, despite the fact that definition of clear/almost and clear differs from study to study

[23].

Moderate to large improvement in disease severity was observed via dynamic photographic PGA starting from week 4. An increase in the percentage of patients with no/almost cleared lesions from 0.0% at baseline to 60.5% at the final visit via static photographic PGA evaluation seem also helpful in the achievement of a more meaningful measure in terms of disease impact.

Indeed, our findings are in line with the statement that using photographs for the assessment of the severity of psoriasis and the treatment response can be a complementary tool, especially for inexperienced dermatologists, in order to observe the effectiveness of biologic treatments [32].

Patients with psoriasis have a significantly impaired quality of life that can lead to a substantial burden in terms of disability or psychosocial stigmatization, depending on the severity [33]. HRQoL is an important aspect of psoriasis, not only in defining disease severity but also as an outcome measure in clinical trials [34].Concomitant assessment of DLQI reveals a useful distinction between severe psoriasis and psoriasis that severely affects the quality of life, which has relevant consequences in terms of disease management [35]. Notably, achievement of better DLQI scores consistent with improved QoL under anti-TNF treatment was shown to predict more favorable outcome in terms of work productivity and activity among psoriasis patients in our cohort.

Since a DLQI score of 0 or 1 has been proposed as a treatment goal [34] which indicates that the HRQoL of the patient is no longer affected by psoriasis, the identification of psoriasis to have no or minimal impact in patients’ lives in 50.0% of patients at week 24 (vs. 2.3% at baseline) emphasizes the positive impact of anti-TNF therapy on patients’ lives in relation to the improvement in the clinical course of the disease.

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With up to a 15.5% work productivity impairment and 23.7% total activity impairment [36,37], the estimated annual indirect costs associated with psoriasis were reported to be greater than $16 billion combining absenteeism and presenteeism far exceeding the estimated direct costs [36].

Moreover, based on a past report indicating a 60% reduction in psoriasis-related work productivity impairment via TNF treatment for a full-time employee working 40 hours per week to be equivalent to an additional 4.4 hours of work productivity compared with baseline (based on the calculation of percentage of total work productivity improvement X 40 h/wk) [28], management of psoriasis via anti-TNF treatment is associated with significant cost savings for employers.

Notably, positive correlation of PASI reductions at week 24 to DLQI reductions (r=0.591; p <0.001) and reductions obtained in absenteeism (r=0.470; p <0.05), presenteeism (r=0.482; p <0.01), work productivity (r=0.451; p <0.01), and activity impairment (r=0.490; p <0.001) components of WPAI at week 24 are in line with the past reports, indicating the likelihood of a correlation between an improvement in PASI and an improvement in DLQI, despite the lack of similar correlation between absolute PASI and absolute DLQI scores [4,38]. According to a 2011 European consensus on the definition of treatment goals for moderate to severe psoriasis [26], in a situation where the therapeutic response improved between 50% and 75%, as assessed by PASI, therapy should be modified if the DLQI is >5 but should be continued if the DLQI is ≤ 5. Therefore, based on identification of ≥ 75% improvement in PASI score in 70.9% of patients while a ≥ 50% but <75% improvement in PASI score accompanied with DLQI of ≤ 5 in 8.1% of patients at week 24, continuation of treatment seems appropriate in 79% of our study population.

Our results support the consistently reported association between the work productivity and disease severity in the literature [36,37] including a positive association between work productivity loss and PASI or DLQI [37], lesser work productivity impairment in patients with mild psoriasis as measured by PGA than those with moderate or severe disease [37], and a higher likelihood of having lower incomes and reporting psoriasis as the reason for not being employed by patients with severe psoriasis compared with mild psoriasis [39].

Given these findings, it is likely that the detrimental effects of psoriasis on work productivity and non-work activities may generally be associated with the increasing psoriasis severity, whereas the impact of anti-TNF treatment on work productivity and activity impairment could largely be attributable to its impact on disease severity [28].

The risks and benefits of biologic therapies relative to standard systemic therapy are largely unknown at present and the widespread use of these agents in uncomplicated moderate to severe psoriasis is inappropriate and is not supported by the licensed indications for these drugs [5]. Along with similar efficacy of three agents in PASI and DLQI improvement in our cohort, our findings support the suggestion of TNF antagonists as a first-line biologic intervention, given the proven efficacy of TNF antagonists in psoriasis, the substantial body of available clinical safety data, and the high proportion of patients with associated psoriatic arthropathy [5].

Nevertheless, it is obvious that long-term disease control frequently requires some form of continuous therapy, and consequently, predictable risks of toxicity [5].

Major limitations of our study were the relatively small number of patients and the short follow-up duration. Therefore, larger scale studies with 2 to 3 years of follow-up period is needed for a better understanding of the safety and efficacy of anti-TNF therapy.

CONCLUSION Our findings indicate that 24-week anti-TNF therapy is safe

and effective in patients for the control of moderate to severe psoriasis, based on the significant reduction in disease severity, disappearance of psoriatic lesions, and improvements in quality of life and work productivity. Along with similar efficacy of different anti-TNF agents in terms of PASI and DLQI reduction, achievement of better DLQI scores was shown to predict more favorable outcome in terms of work productivity and activity among psoriasis patients in our cohort. Nevertheless, for such an elusive and even enigmatic disease, long-term prognostic and interventional studies are necessary for development of better clinimetrics of disease severity in relation to response to treatment, stability of clinical manifestations, as well as psychological outcome.

ACKNOWLEDGEMENTSThis study has been presented as a poster at the 21st Congress

of European Academy of Dermatology and Venereology, 27-30 September, 2012, Prague and at ISPOR 15th Annual European Congress 3-7 November, 2012 ICC Berlin, Berlin, Germany. The study was supported by AbbVie Laboratories Turkey. All authors including those who designed the study and interpreted the data approved the content of this manuscript before submission. Cagla Ayhan, MD, and Prof. Sule Oktay, MD, PhD, from KAPPA Consultancy Training Research Ltd, Istanbul, provided medical writing support, performed statistical analysis that were funded by Abbvie.

Psoriasis Study Group (by the center’s name in descending order of number of patients enrolled):

1. E. Koc (Study Coordinator); Y. Turan, Gulhane Faculty of Medicine, Ankara

2. G. Ozarmagan, P. Kavlak, Istanbul University Istanbul Faculty of Medicine, Istanbul

3. S. Alper, I. Ertan, Ege University Faculty of Medicine, Izmir

4. O. Ozgoztasi, N. Kirtak, Gaziantep University Faculty of Medicine, Gaziantep

5. N.S. Tekin, Karaelmas University Faculty of Medicine, Zonguldak

6. D. Balci, E. Celik, Mustafa Kemal University Faculty of Medicine, Hatay

7. B. Engin, Y. Tuzun, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul

8. N. Onarir, S. Korkmaz, Bezmialem University Faculty of Medicine, Istanbul

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9. N. Atakan, A. Hapa, Hacettepe University Faculty of Medicine, Ankara

10. S. Ozturkcan, C. Bilac, Celal Bayar University Faculty of Medicine, Manisa

11. F. Aydin, H. Tekin, Ondokuz Mayis University Faculty of Medicine, Samsun

12. A. Kokturk, D. Kaya, Mersin University Faculty of Medicine, Mersin

13. N. Kundakci, N. Akay, Ankara University Faculty of Medicine, Ankara

14. M. Ozdemir, A. Balevi, Selcuk University Faculty of Medicine, Konya

15. O. Arican, M. Urun, Trakya University Faculty of Medicine, Edirne

16. E.B. Baskan, S.B. Izol, Uludag University Faculty of Medicine, Bursa

17. M.A. Gurer, M.O. Oztas, Gazi University Faculty of Medicine, Ankara

18. S. Ozcelik, O. Kaya, Cumhuriyet University Faculty of Medicine, Sivas

19. N. Sendur, S. Demirkan, Adnan Menderes University Faculty of Medicine, Aydin

20. A.M. Ceyhan, G. Meric, Suleyman Demirel University Faculty of Medicine, Isparta

21. T. Ergun, D. Seckin, Marmara University Faculty of Medicine, Istanbul

22. S. Karaca, Afyon Kocatepe University Faculty of Medicine, Afyon

23. R. Kiran, S. Bulca, Kocaeli University Faculty of Medicine, Kocaeli

24. M. Kocak, D.O. Kara, Kirikkale University Faculty of Medicine, Kirikkale

25. H. Ozcan, Inonu University Faculty of Medicine, Malatya

CONFLICT OF INTERESTAll authors participated in the study as investigators.

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Koc E, Solak N, Balcı DD, Engin B, Atakan N, et al. (2017) An Observational Study to Evaluate Efficacy and Safety of Anti-TNF Agents in Patients with Moderate to Severe Psoriasis. J Dermatolog Clin Res 5(2): 1098.

Cite this article

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