Sustained improvement in joint pain and nail symptoms with etanercept therapy in patients with moderate-to-severe psoriasis

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1 DOI: /j x JEADV Blackwell Publishing Ltd ORIGINAL ARTICLE Sustained improvement in joint pain and nail symptoms with etanercept therapy in patients with moderate-to-severe psoriasis TA Luger,* J Barker, J Lambert, S Yang, D Robertson, J Foehl, CT Molta, R Boggs Klinik und Poliklinik für Dermatologie, University of Münster, Münster, Germany St Johns Institute of Dermatology (King s College), London, UK University Hospital of Antwerp, University of Antwerp, Antwerp, Belgium Wyeth Research, Collegeville, PA, USA *Correspondence: TA Luger. luger@uni-muenster.de Abstract Background To determine the prevalence of joint and nail symptoms, impact of these symptoms on health-related quality of life (HR-QoL), and the effects of etanercept on them in patients with moderate-to-severe plaque psoriasis. Methods In CRYSTEL, patients with psoriasis received etanercept continuously (n = 357) or as paused therapy (n = 363) for 54 weeks. In post hoc analyses, baseline characteristics and after-treatment changes were evaluated in patients with baseline joint pain or nail psoriasis, pooling across treatment groups. Assessments of symptom severity and HR-QoL included the Subject Global Assessment question on joint pain, NAPSI, DLQI and EQ-5D. Results Of 711 patients, 64% reported joint pain and 79% nail psoriasis at baseline. Patients with baseline joint pain or nail psoriasis had significantly worse HR-QoL than unaffected patients. Mean baseline differences between patients with and without joint pain in DLQI (3.3), EQ-5D utility (0.2), and EQ-5D VAS (7.3) were clinically meaningful. In patients with nail psoriasis, a clinically meaningful difference in EQ-5D VAS (5.0) was seen. Etanercept significantly improved symptom severity and HR-QoL. Patients with joint pain had improvements of 47%, 61%, 29%, and 23% in mean joint pain score, DLQI, EQ-5D utility, and EQ-5D VAS, respectively, at Week 54. Patients with nail psoriasis had improvements of 51%, 63%, and 24% in NAPSI, DLQI, and EQ-5D VAS. Conclusion In this study of moderate-to-severe plaque psoriasis, joint and nail symptoms were prevalent and patients with these symptoms had significantly greater HR-QoL impairment at baseline than unaffected patients. Etanercept provided significant improvement in symptom severity and HR-QoL. Received: 11 December 2008; Accepted 7 January 2009 Keywords etanercept, joints, nails, open-label study, psoriasis, quality of life Conflict of Interest T. Luger has acted as a paid consultant to and speaker for Wyeth Pharmaceuticals. J. Barker has acted as a paid consultant to and speaker for, and has received unrestricted research or education support from Wyeth Pharmaceuticals. J. Lambert has acted as a paid consultant to and speaker for Wyeth. S. Yang, D. Robertson, J. Foehl, C. Molta, and R. Boggs are employed by Wyeth Pharmaceuticals, which supported this study financially. Introduction Psoriasis, a common chronic inflammatory skin disease, is associated with significant morbidity, including impairment in quality of life encompassing functional, psychological, and social dimensions. 1,2 In a recent cross-sectional study of a daily practice psoriasis population, more than one third of patients reported a very or extremely large impairment in health-related quality of life (HR-QoL). 3 The overall impact of psoriasis on quality of life has been shown to be similar to that of major chronic diseases, including cancer, cardiovascular disease, and depression. 4 In addition to pruritic, painful, and disfiguring skin lesions, psoriasis may have other clinical manifestations, such as joint pain and nail abnormalities, that can further interfere with patients well-being and performance of normal daily activities. 5 8 Joint pain appears to be the most common extracutaneous medical condition associated with psoriasis. In a recent prevalence study, rheumatologists found that 33% of psoriatic patients had or had a history of peripheral arthritis and/or axial disease. 9 In an earlier study of patients treated for cutaneous psoriasis, nearly 40% of patients suffered from arthralgia, with 20% receiving a diagnosis of psoriatic arthritis. 10 In a population of psoriasis patients responding to a questionnaire on joint complaints, 53% had a current or past history of arthralgias. 11 Interestingly, in a hospital-based case-control study, entheseal abnormalities documented by ultrasonography

2 Etanercept in psoriasis patients with joint/nail symptoms 897 were also found to be common in patients with psoriasis, in the absence of clinical signs of arthropathy. 12 Previous studies have shown that patients with both psoriasis and psoriatic arthritis have greater impairment in HR-QoL than those with psoriasis alone, 6,7,13 although a more recent report suggested no significant difference. 14 Husted et al. demonstrated that psoriatic arthritis patients had similar or greater difficulties in several aspects of HR-QoL compared with rheumatoid arthritis patients. 15 Nail symptoms have been reported in 10% to 50% of patients with psoriatic skin lesions, 16 with a higher incidence reported in individuals with psoriatic arthritis. 17,18 Although relatively few studies have been conducted to specifically evaluate the additional burden of nail symptoms on quality of life, in a survey of psoriasis patients with nail abnormalities, large proportions of patients reported pain caused by the nail changes (52%) and limitations in their daily activities (59%) and profession (48%). 8 Early detection and treatment of these manifestations of the disease are considered essential to reduce the burden of illness and potential complications. Etanercept is a fully human tumour necrosis factor (TNF) soluble receptor fusion protein that has been shown to be safe and effective for the treatment of moderate-to-severe psoriasis, as well as other inflammatory diseases, including psoriatic arthritis. 19 Randomised, double-blind, placebo-controlled studies in patients with plaque psoriasis have demonstrated that etanercept 25 mg or 50 mg twice weekly or 50 mg once weekly reduces the severity of psoriasis skin symptoms, improves quality of life, and has a favourable safety and tolerability profile In two of the latter studies, skin symptom and quality-of-life improvements were dose dependent, with the etanercept 50 mg twice weekly dose regimen demonstrating greater efficacy than the 25 mg twice weekly regimen over 12 weeks, without an increase in adverse events or infections. 21,22 To further explore variations in etanercept dose regimens that may allow physicians to tailor therapy to the individual needs of patients, the CRYSTEL study compared the efficacy and safety of continuous and paused (intermittent) etanercept dose regimens in patients with moderate-to-severe plaque psoriasis over 54 weeks of open-label treatment. 24 Here, we report the results of post hoc analyses conducted specifically in subsets of the CRYSTEL population that reported joint and nail symptoms at baseline. These subanalyses were performed to determine the frequency and severity of joint and nail symptoms at baseline; the severity of HR-QoL and psychosocial impairment in patients reporting joint and nail symptoms; and the effects of etanercept therapy across treatment groups on symptom/disease severity, HR-QoL, and psychosocial status in those patient subgroups. Materials and methods The methods and study design for CRYSTEL study have been described in detail elsewhere 24 and are briefly summarized here. Study design, patients, and interventions A total of 720 adult patients with moderate-to-severe plaque psoriasis were enrolled in this randomised, open-label, multicentre study. Eligible patients had active but clinically stable plaque psoriasis involving 10% of the total body surface area (BSA) and a Physician Global Assessment of Psoriasis (PGA) of 3 (moderate or worse skin symptoms) at screening and had previously failed usual care. Patients were assigned randomly in a 1 : 1 ratio to receive continuous etanercept therapy administered as 25 mg subcutaneously (SC) twice weekly throughout the 54-week study or paused etanercept therapy initiated at a dose of 50 mg SC twice weekly and continued for a maximum of 12 weeks until the target response (PGA of mild or better [ 2]) was achieved. In the paused therapy group, patients experiencing a relapse (PGA 3) after the discontinuation of therapy received another cycle of etanercept 25 mg SC twice weekly until regaining response, when they again discontinued treatment. This treat-to-target cycle continued throughout the study. Assessments In the post hoc analyses reported here, subgroups of patients with baseline joint pain and nail psoriasis were identified and evaluated for specific symptom severity, overall disease severity, HR-QoL, and psychosocial and employment status. Patients with both of these symptoms were included in both subgroups. Joint pain was assessed at baseline and at each subsequent study visit (weeks 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, and 54) or at early discontinuation, based on responses ranging from 0 (no pain) to 5 (severe pain) to the Subject Global Assessment (SGA) question Over the last week, how severe has your joint pain been? Patients who reported joint pain greater than 0 at baseline were evaluated in the subanalyses reported here. Physicians assessed nail psoriasis using the Nail Psoriasis Severity Index (NAPSI) 25 at baseline and at specified intervals throughout the study (weeks 12, 24, 36, and 54), or at the time of discontinuation. NAPSI scores range from 0 (no nail psoriasis) to 8 (severe nail psoriasis). Patients with a NAPSI score of at least 1 at baseline were included in these subanalyses. Overall disease severity was evaluated at baseline and at subsequent study visits through 54 weeks, or discontinuation, using the Psoriasis Area and Severity Index (PASI) 26 and BSA. Patientreported outcomes used to examine HR-QoL and psychosocial status included the Dermatology Life Quality Index (DLQI), EuroQoL-5D (EQ-5D), the Short-Form 36 (SF-36) Health Survey Vitality domain, and the Hospital Anxiety and Depression Scale (HADS). The DLQI was administered to patients at baseline and at each subsequent study visit, or early discontinuation. The DLQI, a validated instrument used in the clinical dermatology setting, assesses the impact of skin disease on 6 aspects of HR-QoL: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment This instrument is not designed to measure quality of life impairment due to joint symptoms. Scores range from 0 to 30, with 0 indicating no impairment in dermatology-specific quality of life and higher scores indicating greater impairment. DLQI scores 10 represent serious impairment. 30 Changes in DLQI ranging from 2.3 to 5.7

3 898 Luger et al. have been identified as possible thresholds of clinically meaningful change. 31 The EQ-5D was administered at baseline and weeks 12, 24, 36, and 54, or at withdrawal from the study. The EQ-5D was designed to compare health states across diseases. It includes a utility index and a thermometer-like Visual Analogue Scale (VAS). The EQ- 5D utility index determines the extent of a patient s impairment from a societal perspective based on his or her mobility, pain/ discomfort, anxiety/depression, ability to care for himself or herself and to perform usual activities. Scores range from 0 (death) to 1 (perfect health), with changes of 0.05 considered clinically meaningful. 32 The EQ-5D VAS allows patients to judge their own health, with scores ranging from 0 (worst imaginable health state) to 100 (best imaginable health state); changes of 4 8 are considered minimal important differences (MIDs). 31,33,34 Patients completed the Vitality domain of the SF-36 Health Survey at baseline and weeks 12, 24, 36, and 54, or at early discontinuation. The SF-36 Health Survey is a general health status instrument that has demonstrated good reliability and validity in descriptive and clinical studies in psoriasis Vitality scores can range from 0 to 100, with higher scores representing more vitality. Changes of 5 10 points are estimated to be MIDs in SF-36 Vitality scores. 38 Depression and anxiety were evaluated at baseline and weeks 12, 24, 36, and 54 using the HADS, a 14-item self-administered questionnaire evenly weighted for these symptoms. 39 The scale is intended to assess symptoms and not to diagnose disease. Both the Depression subscale (HADS-D) and the Anxiety subscale (HADS-A) have scores ranging from 0 to 21, with higher scores indicating worse symptoms. Patients with scores of 8 10 are considered to have mild symptoms of depression or anxiety. Statistical analysis Post hoc analyses were performed, dividing patients into subgroups based on the presence of joint pain and nail psoriasis at baseline. For demographic characteristics and the measures described above, mean scores were computed by subgroup, pooling patients receiving continuous and paused therapy together; patients who had joint pain and nail psoriasis were compared with those who did not have these symptoms using t-tests for independent samples. For each subgroup, baseline scores for symptoms measured by continuous scales were compared with end-of-treatment scores using paired t-tests. The proportions of patients with joint pain who also had nail symptoms were compared using chi-squared tests. Multivariate regressions were used to control for age, gender, baseline PASI and disease duration when determining whether a problem observed at baseline (joint pain or nail psoriasis) was associated with other symptoms and HR-QoL/psychosocial measures observed at baseline. The null hypotheses were that there were no differences among groups being compared. All tests were two tailed, and a difference was considered statistically significant when alpha was 0.05 or less. These tests did not control for multiple comparisons. Results Baseline observations At baseline, patients with joint pain or nail psoriasis had significantly worse HR-QoL than patients without these manifestations of the disease; those with joint pain also demonstrated significantly worse psychosocial status (Table 1; Fig. 1a c). Table 1 Baseline demographic and disease characteristics of patients with and without baseline joint pain and nail psoriasis Patients with joint pain (n = 452) Demographic characteristics Patients without joint pain (n = 255) P Patients with nail psoriasis (n = 564) Patients without nail psoriasis (n = 145) Age, years Male, % < Disease duration, years Symptom/overall disease severity SGA, joint pain score < NAPSI < BSA PASI < HR-QoL and psychosocial function DLQI < EQ-5D utility < EQ-5D VAS SF-36 Vitality < HADS-D < HADS-A < All values are means, unless otherwise noted. P

4 Etanercept in psoriasis patients with joint/nail symptoms 899 Figure 1 (a) Mean DLQI at baseline and after etanercept therapy in patients with and without joint pain and nail psoriasis at baseline. *P < , patients with joint pain vs. patients without joint pain at baseline; P = , patients with joint pain vs. patients without joint pain after etanercept therapy; P = , patients with nail psoriasis vs. patients without nail psoriasis at baseline. (b) Mean EQ-5D utility scores at baseline and after etanercept therapy in patients with and without joint pain and nail psoriasis at baseline. *P < , patients with joint pain vs. patients without joint pain at baseline and after etanercept therapy. (c) Mean EQ-5D VAS scores at baseline and after etanercept therapy in patients with and without joint pain and nail psoriasis at baseline. *P = , patients with joint pain vs. patients without joint pain at baseline; P < , patients with joint pain vs. patients without joint pain after etanercept therapy; P = , patients with nail psoriasis vs. patients without nail psoriasis at baseline. Joint pain Although joint pain was not a study inclusion criterion, 64% of patients reported having joint pain at baseline. Among those with joint pain, the mean baseline joint pain score was 2.76 (0 = no pain; 5 = severe pain). Patients with joint pain were slightly older than patients without joint pain (45.9 years vs years, P = 0.016), and a greater proportion of those with joint pain were female (31.0% vs. 23.9%, P = 0.046). Patients with joint pain also had slightly greater PASI at baseline than other patients (22.9 vs. 21.4, P = 0.047). Patients with joint pain had worse baseline DLQI, EQ-5D utility, EQ-5D VAS, SF-36 Vitality, and HADS-D/HADS-A than joint painfree patients (P < for all measures). The mean difference in total DLQI of 3.3 appeared to be clinically meaningful. Differences were statistically significant in all DLQI domains (P < 0.001; Fig. 2a), with the greatest differences observed in the domains for work and school (56%), personal relationships (43%), daily activities (31%), and difficulties with treatments received immediately prior to randomization (31%). Differences in EQ-5D utility between patients with baseline joint pain and other patients were approximately four times the accepted MID. Differences were statistically significant for all 5 questions that comprise the utility score (P ), with the greatest differences in mean scores for pain/discomfort (33%),

5 900 Luger et al. Table 2 Improvements in symptom and overall disease severity and HR-QoL/psychosocial status with etanercept therapy after 54 weeks in patients with and without baseline joint pain and nail psoriasis Patients with joint pain Symptom/overall disease severity Patients without joint pain P Patients with nail psoriasis Patients without nail psoriasis SGA, joint pain score < NAPSI < BSA PASI (% improvement) HR-QoL and psychosocial function DLQI EQ-5D utility EQ-5D VAS SF-36 Vitality HADS-D HADS-A All values are means, unless otherwise noted. P mobility (28%), and ability to participate in usual activities (23%). The baseline difference of 7.3 in EQ-5D VAS also appeared to be clinically meaningful but less dramatic than EQ-5D utility. The baseline difference in the SF-36 Vitality score of 11.5 between patients with joint pain and other patients was greater than the MID of 5 10 points for that measure. 38 In addition, patients with joint pain at baseline had significantly worse baseline HADS-D (6.6) and HADS-A (8.2) scores than patients without joint pain (4.73 and 6.0, respectively; P < 0.001). After controlling for age, gender, baseline PASI and disease duration, patients with baseline joint pain still had worse scores than other patients in DLQI, EQ-5D utility and VAS, SF-36 Vitality, and HADS-D and HADS-A (P < for all measures). Nail psoriasis Most patients (79%) in this study also had nail psoriasis at baseline. The mean baseline NAPSI score among this subgroup of patients was Patients with nail psoriasis were more likely to be male than patients without nail psoriasis (75.4% vs. 57.2%, P < 0.001). Among all male patients in the CRYSTEL study (n = 508), 83.7% had nail psoriasis at baseline; among all female patients (n = 201), 69.2% had nail symptoms at baseline. In addition, patients with nail psoriasis had greater BSA involvement (39.56 vs , P = 0.003) and had worse baseline PASI scores (23.2 vs. 19.2, P < ). Patients with nail psoriasis at baseline also had worse baseline DLQI and EQ-5D VAS scores than other patients (P = and 0.017, respectively), although the difference in DLQI (1.44) did not appear to be clinically meaningful. 31 The presence of nail symptoms was associated with greater impairment in all DLQI domains except daily activities (Fig. 2b); however, the differences in domain scores between patients with and without nail symptoms were not significant (P 0.053). The difference in EQ-5D VAS of 5.0 was within the estimated MID range for that measure. 31 Controlling for gender, patients with nail psoriasis at baseline still had worse DLQI and EQ-5D VAS than other patients (P = and 0.011, respectively). The DLQI results continued to hold when controlling for baseline PASI and disease duration as well as gender (P = 0.028), but the EQ-5D VAS difference was no longer statistically significant when controlling for these covariates (P = 0.088). Approximately 52% (370 of 705, with six patients missing either NAPSI or SGA joint pain scores at baseline) of patients included in these subanalyses had both joint pain and nail symptoms. Baseline joint pain was found to be associated with baseline nail psoriasis (P = 0.044), with 82% (370/452) of joint pain patients having nail psoriasis and 66% (370 of 561) of nail psoriasis patients having joint pain. Improvements with etanercept therapy Etanercept therapy significantly reduced patients symptom and overall disease severity and improved HR-QoL and psychosocial status (Table 2; Figs 1a c and 3). Joint pain All measures noted above as being worse for patients with joint pain at baseline were improved after treatment with etanercept (54 weeks for most patients; P < for all measures). In this subgroup, joint pain scores decreased from 2.76 at baseline to 1.76 at week 3, an improvement of 36.2% (P < 0.001). Mean joint pain improved by 1.29 (47%) across the two etanercept treatment groups at the study s end, with 34.1% of patients who had baseline joint pain reporting no end-of-treatment joint pain. At the end of the study, DLQI improved by 8.86 (61%); EQ-5D utility improved by 0.17 (29%); EQ-5D VAS improved by (23%); and SF-36 Vitality improved by 5.55 (11%). Mean HADS- D scores improved by 1.9 (29%) in patients with baseline joint pain and mean HADS-A improved by 2.27 (28%).

6 Etanercept in psoriasis patients with joint/nail symptoms 901 Figure 2 (a) Mean scores for six DLQI domains at baseline in patients with and without joint pain at baseline (range of scores: 0 6 for symptoms and feelings, daily activities, leisure, and personal relationships domains; 0 3 for work or school and treatment domains). *P < (b) Mean scores for six DLQI domains at baseline in patients with and without nail psoriasis at baseline (see above for range of scores). When analysing only those measures that were worse among patients in the joint pain subgroup at baseline, patients with joint pain had greater improvement than patients without joint pain in DLQI, EQ-5D utility, and HADS-D and HADS-A after treatment with etanercept (P 0.019). However, despite these gains, at the end of the study, patients who had baseline joint pain continued to have worse scores than other patients on the SGA joint pain measure, DLQI, EQ-5D utility and EQ-5D VAS, as well as the HADS-D and HADS-A (P < for all measures). Nail psoriasis In the subgroup of patients with nail psoriasis at baseline, NAPSI scores decreased from 4.64 at baseline to 3.30 at week 12 (the first postbaseline assessment), an improvement of 28.9% (P < 0.001). An improvement in NAPSI of 2.38 (51%) was observed at week 54, with 30% of patients with nail psoriasis at baseline reporting no nail psoriasis at the end of treatment. Patients in this subgroup also showed significant and clinically meaningful improvement with etanercept therapy in DLQI and EQ-5D VAS the measures for which they had worse scores than others at baseline (P < 0.001). After treatment, patients who had nail psoriasis at baseline also showed greater improvement in DLQI and EQ-5D VAS than other patients (P = and 0.008, respectively). At week 54, no significant differences remained between patients with and without nail psoriasis in DLQI and EQ-5D VAS (P > for both measures), although the NAPSI remained worse in patients with

7 902 Luger et al. Figure 3 Changes in mean symptom scores (SGA joint pain score and NAPSI) in patients with respective symptoms at baseline from baseline through Week 54. P < , etanercept compared with baseline at all time points for all scores. baseline nail psoriasis than in other patients (P < 0.001). PASI scores at the end of treatment were similar between those patients with nail psoriasis and those without nail psoriasis (8.5 vs. 7.6, P = 0.263). Discussion Joint and nail symptoms occurred at baseline in large proportions of the patients with moderate-severe plaque psoriasis evaluated in this study 64% and 79%, respectively. Our analyses showed that joint and nail symptoms were not only very common in this population of psoriasis patients but also caused significant HR- QoL impairment in these patients. EQ-5D utility scores for patients with baseline joint pain suggested their health state was similar to that of patients with rheumatoid arthritis. 40 They reported worse problems with work or school, daily activities, personal relationships, and prior treatments, more pain/discomfort, and less mobility than other patients in this study. Patients with nail psoriasis at baseline also had worse HR-QoL than patients without nail symptoms in this trial, although the difference was not as marked as with joint pain. Etanercept therapy provided rapid and consistent improvement among patients with joint and nail symptoms at baseline. By the end of the treatment period, patients with joint pain at baseline showed significantly greater improvement in DLQI, EQ-5D utility, and depression and anxiety scores than other patients. Similarly, patients with nail psoriasis at baseline had significantly greater improvement after receiving etanercept therapy than other patients in the HR-QoL measures that were greater problems for them at baseline. The primary analyses of quality-of-life endpoints in these post hoc analyses were comparisons of patients who had a specific symptom (joint pain or nail psoriasis) vs. those who did not. Such analyses were intended to inform practicing dermatologists about the relative quality of life of patients with these symptoms regardless of their age, gender, or extent of their psoriasis. A criticism of this approach is that the HR-QoL differences can be attributed to the fact that patients with joint pain tend to be older, or patients with nail psoriasis have more extensive skin disease. Secondary analyses controlling for these issues generally still showed that patients with joint pain or nail psoriasis had worse quality of life. In these post hoc analyses, patients with joint pain and nail symptoms were pooled across the two etanercept treatment groups. Comparisons between the two groups for safety and efficacy including all patients in this study have been reported 24 and between-group comparisons for patient-reported outcomes will be available in a future publication. Broadly, almost all patient-reported outcomes showed statistically significant and clinically meaningful improvements from baseline for both groups; differences between groups were sometimes statistically significant but not clinically meaningful. Similar comparative results could be reported for the subgroups of patients with joint pain or nail symptoms. However, the purpose of this paper was to identify whether these subgroups had greater HR-QoL impairment at baseline and whether this impairment was alleviated with treatment, regardless of the etanercept regimen administered. Determining the prevalence of psoriatic arthritis in this population was not a pre-specified objective of this clinical trial; tender and swollen joint counts were not recorded. Therefore, it is unclear how many of the patients reporting joint pain had psoriatic arthritis and how many had osteoarthritis or other conditions. In a recent systematic review of prevalence and incidence studies of psoriatic arthritis in the general population, Alamanos et al. reported a median annual incidence of 6.4 cases per (range, ), with important variations among countries and global areas, but cautioned that interpretation of epidemiological data is limited by methodological issues, particularly the absence of standardized criteria for disease identification. 41 Among patients with psoriasis, an estimated 6% to 40% have psoriatic arthritis Patients in this study are not representative of all psoriasis patients. Inclusion/exclusion criteria selected patients with moderate to severe psoriasis who had failed usual care. Therefore, the prevalence of joint pain seen in this study estimates that expected for patients eligible for biological therapy rather than psoriasis patients in general. In addition to a high prevalence of joint and nail abnormalities in patients with psoriasis, the associated HR-QoL burden, and the significant benefits of etanercept therapy, we found that the presence of joint symptoms at baseline was significantly associated with that of nail psoriasis an association not widely disseminated in the literature. Psoriasis patients are typically unaware of the potential relationship between joint pain and their skin disease and are therefore not likely to report arthritis symptoms to their dermatologists. Along with thorough clinical evaluation, simple screening tools, such as the Psoriatic Arthritis Screening and

8 Etanercept in psoriasis patients with joint/nail symptoms 903 Evaluation questionnaire, 46 may be valuable in the dermatology setting to identify psoriasis patients at increased risk for psoriatic arthritis. In addition, it is interesting to note that male gender was also significantly associated with nail psoriasis, a finding not previously seen in the literature. In conclusion, these post hoc analyses of the CRYSTEL study show joint pain and nail psoriasis were prevalent in these moderateto-severe psoriasis patients and that these patients had a worse quality of life than patients whose disease was not complicated by these symptoms. Treatment with etanercept significantly improved symptoms, HR-QoL, and psychosocial function in patients with joint pain and nail symptoms, with generally greater improvements observed than in patients without these symptoms. Because of the prevalence of joint and nail symptoms in moderate-tosevere plaque psoriasis and their impact on patients quality of life and psychological well-being, dermatologists should evaluate these symptoms and ensure that these patients are adequately treated. Acknowledgement This study was supported by Wyeth Research, Collegeville, PA. The authors would like to thank the patients who participated in the CRYSTEL study (study 909) and the investigators and medical staff of all participating centers. In addition, we would like to acknowledge Joanne Estojak, MS, for supporting the study conduct and monitoring; Xuesong Zhang, MS, for conducting statistical analyses; and Donna McGuire, BA, for assistance with the preparation and review of the manuscript. References 1 Smith CH, Barker JN. Management of psoriasis. BMJ 2006; 333: Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet 2007; 370: Augustin M, Krüger K, Radtke MA et al. 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