Research ArticleArticle

Improvement in Psoriasis Signs and Symptoms Assessed by the Psoriasis Symptom Inventory with Brodalumab Treatment in Patients with Psoriatic Arthritis

Philip J. Mease, Mark C. Genovese, Alex Mutebi, Hema N. Viswanathan, Dina Chau, Jingyuan Feng, Ngozi Erondu and Ajay Nirula
The Journal of Rheumatology February 2016, 43 (2) 343-349; DOI: https://doi.org/10.3899/jrheum.150182

Abstract

Objective. To evaluate the effect of brodalumab on psoriasis signs and symptoms assessed by the Psoriasis Symptom Inventory (PSI) in patients with psoriatic arthritis (PsA).

Methods. This prespecified analysis of a phase II study (NCT01516957) evaluated patients with active PsA and psoriasis-affected body surface area ≥ 3%, randomized to brodalumab (140 or 280 mg) or placebo every 2 weeks (Q2W) for 12 weeks with loading dose at Week 1. At Week 12, patients entering an open-label extension received brodalumab 280 mg Q2W. The PSI measures 8 psoriasis signs and symptoms: itch, redness, scaling, burning, stinging, cracking, flaking, and pain. PSI response is defined as total PSI ≤ 8 (range 0–32), each item ≤ 1 (range 0–4). PSI scores were assessed at weeks 12 and 24.

Results. There were 107 eligible patients. At Week 12, mean improvement in PSI scores was 7.8, 11.2, and 1.5 in brodalumab 140 mg, 280 mg, and placebo groups, respectively; by Week 24, improvement was 10.2, 12.4, and 11.7. At Week 12, 75.0%, 81.8%, and 16.7% of patients receiving brodalumab 140 mg, 280 mg, and placebo, respectively, achieved PSI response; improvement was sustained through Week 24, when 83.9% of prior placebo recipients achieved response. At Week 12, 25.0%, 36.4%, and 2.8% of patients receiving brodalumab 140 mg, 280 mg, and placebo, respectively, achieved PSI 0. Percentages improved through Week 24: 40.0% brodalumab 140 mg, 42.9% brodalumab 280 mg, and 48.4% placebo.

Conclusion. Significantly more brodalumab-treated patients with PsA achieved patient-reported improvements in psoriasis signs and symptoms than did those receiving placebo. Improvements were comparable between brodalumab groups.

Key Indexing Terms:

Psoriatic arthritis (PsA) is an inflammatory disease that frequently presents with cutaneous symptoms associated with psoriasis and inflammatory joint disease1,2,3. Prevalence of PsA among patients with psoriasis varies widely and is estimated to be between 6% and 42%1,2,4,5. The clinical features of PsA include psoriasis, arthritis, dactylitis, enthesitis, spondylitis, and nail disease6. Most patients with PsA have active psoriasis or have had a history of psoriasis7, and as PsA progresses, joint damage associated with arthritis increases1,7,8,9. Psoriasis symptoms in patients with PsA are likely to be associated with a greater effect on health-related quality of life (HRQOL)10,11: patients with psoriasis who also have PsA have worse health status and lower HRQOL than patients with psoriasis alone, as measured by the Health Assessment Questionnaire (HAQ), the Medical Outcomes Study Short Form-36 (SF-36) questionnaire, the Dermatology Life Quality Index (DLQI), and EQ-5D12,13. Patients with PsA with mild psoriasis are believed to experience minimal effect on quality of life, whereas patients with moderate to severe psoriasis experience a more than minimal effect on quality of life14.

Interleukin (IL)-17 pathways may play a role in the pathogenesis of autoimmune diseases, including PsA, psoriasis, and ankylosing spondylitis15,16,17,18,19,20,21. This family of cytokines [including IL-17A, IL-17F, IL-17E (IL-25), and IL-22] is produced by Th17 and other immune cells, which are themselves induced by IL-2322,23. These proinflammatory cytokines then induce a cascade of downstream activities, including the production of additional proinflammatory cytokines and chemokines and antimicrobial peptides24,25,26. Patients with PsA have high expression of Th17 cells in peripheral blood and of IL-17 receptor antagonist (IL-17RA) in synovial fluid27,28. Brodalumab, a human monoclonal antibody against IL-17RA, blocks the signaling of multiple IL-17 cytokines including IL-17A, IL-17F, and the IL-17A/F heterodimer29. In a phase II, randomized controlled trial, patients with PsA treated with brodalumab experienced significant clinical benefit, as measured by 20% and 50% improvements in American College of Rheumatology response criteria (ACR20 and ACR50, respectively)30.

Patient-reported outcomes (PRO) provide critical information about patient perception of treatment benefit and disease status that complements clinical assessments31,32. The Psoriasis Symptom Inventory (PSI) is a newly developed, 8-item PRO instrument of psoriasis signs and symptom severity assessing itch, redness, scaling, burning, stinging, cracking, flaking, and pain31,33,34,35. The development of the PSI was informed by a review of the literature, clinician input, and extensive involvement of patients with psoriasis, some of whom had PsA. Data from various analyses have shown the PSI to be a reliable and valid measure of psoriasis signs and symptom severity in patients with psoriasis and PsA34,35,36. In addition, the PSI is able to detect clinically meaningful change in psoriasis signs and symptom severity, because it closely correlates with improvements in Psoriasis Area and Severity Index (PASI) and static physician’s global assessment (sPGA) of disease scores33,35. We sought to evaluate the effect of brodalumab on psoriasis symptoms as assessed by the PSI exclusively in patients with PsA.

MATERIALS AND METHODS

Patients

Patients were eligible to participate in our study if they were between the ages of 18 and 75 years with a diagnosis of PsA as defined by the Classification for Psoriatic Arthritis criteria (CASPAR), had at least 3 tender joints, and had at least 3 swollen joints for a minimum of 6 months. Patients were allowed to use methotrexate (≤ 25 mg/week), leflunomide (≤ 20 mg/day), corticosteroids (≤ 10 mg/day), or nonsteroidal antiinflammatory drugs if they had been on a stable dosage for at least 4 weeks before initiation of study drug. Patients with prior anti-tumor necrosis factor (anti-TNF) therapy and anti-IL-12/23 drug therapy were eligible for the study after washout periods of 2 months for anti-TNF therapy and 3 months for anti-IL-12/23 drug therapy.

Patients were excluded from the study if they had a recent infection (active infection within 28 days or serious infection within 8 weeks), recurrent infection, major chronic inflammatory or connective tissue disease, clinically significant systemic disease, or history of cancer (other than in situ cervical cancer, in situ breast ductal cancer, or successfully treated nonmelanoma skin cancers) within the past 5 years. Patients were required to have had a negative test result for tuberculosis or receipt of prophylactic treatment.

Study design

This was a prespecified analysis of a phase II, randomized, double-blind, placebo-controlled study (NCT01516957) of patients with PsA. The study design has been described30 and is summarized in Figure 1. Patients were randomized 1:1:1 to receive brodalumab 140 mg, brodalumab 280 mg, or placebo at weeks 0, 1, 2, 4, 6, 8, and 10. At Week 12, patients had the option of entering the open-label extension (OLE) period, during which all patients received brodalumab 280 mg Q2W (patients initially randomized to placebo received a loading dose of brodalumab 280 mg at Week 13).

Figure 1.
Figure 1.

Study design. This was a prespecified analysis of a randomized, double-blind, placebo-controlled, phase II study. SC: subcutaneous; Q2W: every 2 weeks.

Outcome measures

The PSI measures patient-reported psoriasis signs and symptom severity on the basis of 8 items: itch, redness, scaling, burning, stinging, cracking, flaking, and pain33,34,35. Each item yields a severity score on a 5-point scale (0 = not at all, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe), and the item scores are summed to yield a PSI total score ranging from 0 to 32. There are 2 recall versions of the PSI — 24-h recall and 7-day recall — that have been shown to yield comparable data31. This phase II study used the 7-day recall version. Patients are considered PSI responders if they achieve a PSI total score no higher than 8, with no item score above 1. Improvement in psoriasis symptoms was assessed by changes from baseline in PSI total and item scores at weeks 12 and 24, percentage of patients who achieved PSI responder status at weeks 12 and 24, and percentage of patients who achieved a PSI total score of 0 (i.e., not at all severe for all 8 signs and symptoms of the PSI) at weeks 12 and 24.

Statistical analyses

Analyses were based on observed PSI scores for patients with baseline affected body surface area (BSA) of at least 3%, without adjusting for multiple testing. For PSI total and item scores, an analysis of covariance model was used to assess the efficacy of brodalumab compared with placebo after adjusting for stratification factors (prior biologic use: yes vs no; baseline weight groups: > 100 kg vs ≤ 100 kg) and baseline values. For the percentage of patients who achieved PSI responder status and PSI total score of 0, the comparison between treatment arms and placebo was performed using a Cochran-Mantel-Haenszel test, which stratified results by prior biologic use and baseline weight.

RESULTS

Patients

The study population has been described in a separate publication30. Of the 168 patients who enrolled in the study, 107 had a baseline BSA involvement of at least 3% and were eligible for this analysis. Of these 107 patients, 99 entered the OLE period at Week 12 and 92 reached Week 24. Key demographics and baseline clinical characteristics are provided in Table 1.

View this table:
Table 1.

Demographics and clinical characteristics at baseline. Data are mean (SD) unless otherwise indicated.

Changes in PSI scores

Improvements in PSI score were observed as early as 2 weeks after the initiation of brodalumab treatment. At all timepoints measured from initiation of study drug to Week 12, patients in both brodalumab treatment groups had significantly greater mean change in PSI total score compared with patients receiving placebo (p ≤ 0.0001 for all timepoints in both brodalumab treatment groups; Figure 2). At Week 12, the mean improvement in PSI total scores was 7.8 for brodalumab 140 mg Q2W and 11.2 for brodalumab 280 mg Q2W compared with 1.5 for placebo (p < 0.0001 for both brodalumab treatment groups; Figure 2). By Week 24, after initiation of the OLE period, during which all patients received brodalumab 280 mg Q2W, the mean improvement in PSI total scores was comparable between brodalumab-treated patients who were initially randomized to placebo and those who were initially randomized to brodalumab. Patients initially randomized to placebo experienced a mean improvement of 11.7 compared with 10.2 (brodalumab 140 mg Q2W) and 12.4 (brodalumab 280 mg Q2W).

Figure 2.
Figure 2.

Changes in PSI total score at baseline, Week 12, and Week 24. Patients randomized to placebo (yellow diamond), brodalumab 140 mg Q2W (green square), and brodalumab 280 mg Q2W (black triangle) reported improvements in their psoriasis symptoms, as measured by the PSI, at the timepoints indicated. After Week 12, all patients initiated the OLE period, during which they received brodalumab 280 mg Q2W, indicated by the dotted line. Results shown are mean (SE) change in PSI total score. P ≤ 0.0001 between brodalumab 140 mg and placebo, and brodalumab 280 mg and placebo at weeks 2, 4, 8, and 12. PSI: Psoriasis Symptom Inventory; Q2W: every 2 weeks; OLE: open-label extension; SE: standard error.

Significant improvements were observed for individual items measured by the PSI. By Week 12, patients in both brodalumab treatment groups had significantly greater improvement in each of the PSI items when compared with patients in the placebo group (p ≤ 0.0031 for all items in Table 2). Significant changes in mean item scores for all items were observed as early as 2 weeks in both treatment groups (p ≤ 0.04 for all; data not shown).

View this table:
Table 2.

Change in PSI item scores from baseline at weeks 12 and 24.

PSI responders

Treatment with brodalumab resulted in a higher proportion of PSI responders compared with the placebo group at Week 12. The percentages of PSI responders were 75.0% and 81.8% in the brodalumab 140 mg Q2W and 280 mg Q2W treatment groups, respectively. Moreover, the percentages of PSI responders in the brodalumab groups were significantly higher than in the placebo group (16.7%; p < 0.0001 for both brodalumab treatment groups; Figure 3). During the OLE period, when all patients received brodalumab 280 mg Q2W, 83.9% of patients initially randomized to placebo, 80.0% of those initially randomized to brodalumab 140 mg Q2W, and 75.0% of those initially randomized to brodalumab 280 mg Q2W achieved a response by Week 24 (Figure 3). During the OLE, the percentage of PSI responders among patients who switched from placebo to brodalumab was comparable to the percentages of PSI responders from either group of patients treated with brodalumab throughout the study. During the same period, the proportions of PSI responders were maintained among patients initially randomized to brodalumab 140 mg Q2W and 280 mg Q2W.

Figure 3.
Figure 3.

Percentages of patients who were PSI responders at weeks 12 and 24. The percentages of patients receiving placebo (yellow), brodalumab 140 mg Q2W (green), or brodalumab 280 mg Q2W (black) who were PSI responders at Week 12 are indicated by solid bars. During the OLE period, when all patients received brodalumab 280 mg Q2W, the percentages of patients who were PSI responders at Week 24 are indicated by hatched bars. PSI responders are defined as patients with a PSI total score ≤ 8 and each item score ≤ 1. PSI: Psoriasis Symptom Inventory; Q2W: every 2 weeks; OLE: open-label extension.

PSI score of 0

Within 12 weeks of brodalumab treatment, significantly higher percentages of patients receiving brodalumab 140 mg Q2W (25.0%) and 280 mg Q2W (36.4%) achieved a PSI total score of 0 than did patients receiving placebo (2.8%; p < 0.01 for both brodalumab treatment groups; Figure 4). After initiation of the OLE period, additional patients attained a PSI score of 0 at Week 24 in all groups (Figure 4): 48.4% of patients initially randomized to placebo, 40.0% of patients initially randomized to brodalumab 140 mg Q2W, and 42.9% of patients initially randomized to brodalumab 280 mg Q2W.

Figure 4.
Figure 4.

Percentages of patients with PSI total score of 0 at weeks 12 and 24. The percentages of patients receiving placebo (yellow), brodalumab 140 mg Q2W (green), or brodalumab 280 mg Q2W (black) who attained a PSI total score of 0 at Week 12 are indicated by solid bars. During the OLE period, when all patients received brodalumab 280 mg Q2W, the percentages of patients who attained a PSI total score of 0 at Week 24 are indicated by hatched bars. PSI: Psoriasis Symptom Inventory; Q2W: every 2 weeks; OLE: open-label extension.

DISCUSSION

In our study, treatment with brodalumab resulted in improvement of psoriasis signs and symptoms in patients with PsA, as measured by the PSI. Improvements in PSI total and item scores were observed as early as Week 2; by Week 12, the majority of patients receiving brodalumab achieved PSI responder status and more than 25% of patients achieved a PSI total score of 0. These improvements in symptoms assessed by the PSI were similar between patients in the 2 brodalumab treatment groups. Improvements in psoriasis symptoms within 12 weeks for patients with PsA are similar to improvements found in previous studies of patients with moderate to severe psoriasis33. The percentage of placebo-treated patients who achieved PSI responder status in this study at Week 12 (16.7%) is comparable to that of a previous study reporting that 13.2% of placebo-treated patients with moderate to severe plaque psoriasis achieved PSI responder status29.

Patients continued to experience improvements in psoriasis symptoms during the OLE period of the study. By Week 24, after switching to brodalumab 280 mg Q2W at Week 12, the majority of patients initially randomized to placebo attained improvements in PSI total score comparable to those achieved by patients initially randomized to brodalumab. The proportion of patients initially randomized to placebo who achieved PSI responder status and a PSI total score of 0 was similar to that of patients who received brodalumab throughout the study. Additional clinical benefit from treatment with brodalumab continued beyond Week 12, as shown by the additional patients in the brodalumab groups who achieved a PSI total score of 0 from Week 12 to Week 24.

PRO instruments are relevant and useful tools to measure patient-reported symptoms and treatment benefit. The use of both PRO and physician evaluations provides a complementary approach to evaluating treatment outcomes32,37. The PSI is a newly developed, psoriasis-specific PRO instrument that assesses the severity of psoriasis signs and symptoms. The PSI was developed in accordance with the recommendations set forth by the US Food and Drug Administration PRO Guidance38 and has demonstrated excellent content and construct validity34,35. In addition to the PSI, several other PRO instruments have been used to evaluate patient-reported psoriasis signs and symptom experiences, albeit with limitations32,39. There is an increasing body of evidence to confirm the good measurement properties of the PSI in patients with psoriasis and PsA31,33,34,35,36. Collectively, these analyses support the use of the PSI to capture the severity of psoriasis-specific signs and symptoms and to evaluate treatment benefits as a complement to physician assessments both in clinical trials and clinical practice.

Published evidence supports the reliability and validity of the PSI to detect changes highly correlated with PASI and sPGA scores35. The findings from this analysis have further shown a significant therapeutic benefit of brodalumab treatment in patients with PsA. This therapeutic benefit of brodalumab as measured by the PSI mirrors improvements reported in other studies using clinical assessments such as PASI, sPGA, ACR20, Clinical Disease Activity Index, and 28-joint Disease Activity Score30,31,33,35.

The present analysis is not without its limitations. First, this analysis was based on results from a single randomized controlled trial and may not be generalizable to broader populations. Second, the “as-observed” analysis may limit statistical interpretation of the findings. However, completion rates for the PSI were high, and the use of as-observed analyses informed a robust analysis of the data. Third, most of the currently published evidence supporting the good measurement properties of the PSI is based on analyses of data from patients with moderate to severe plaque psoriasis, with relatively less published evidence supporting the use of the PSI in PsA. Whereas the measurement properties of the PSI in PsA have not yet been extensively evaluated, data from our study have been analyzed to assess the reliability and construct validity of the PSI in PsA and will be published separately. This analysis included only patients with at least 3% psoriasis-affected BSA because the PASI does not perform well at that lower scale40; understanding the responsiveness of the PSI at a BSA below 3% will be worth exploring in future research. Finally, the effect of brodalumab on improvement of psoriasis signs and symptoms would have been better understood if additional skin-related assessments such as PASI had been included in this trial. Ongoing phase III trials include additional skin-related assessments, which are expected to provide a more complete evaluation of the effect of brodalumab in patients with PsA.

Brodalumab therapy improves psoriasis signs and symptoms in patients with PsA. Improvements in all signs and symptoms measured by the PSI were apparent as early as 2 weeks after initiation of treatment. Patients in the brodalumab treatment groups experienced significantly greater improvements in psoriasis signs and symptom severity than patients in the placebo group. A significantly higher proportion of patients treated with brodalumab compared with patients treated with placebo achieved PSI responder status and a PSI total score of 0, indicating no severe psoriasis signs and symptoms.

Treatment benefit from brodalumab was evident and maintained throughout the OLE period. This analysis further supports the use of brodalumab for the treatment of psoriasis signs and symptoms in patients with PsA.

Acknowledgment

We thank Jessica Ma, PhD (Amgen Inc.), for medical writing support and Jon Nilsen, PhD (Amgen Inc.), for graphics support.

Footnotes

  • Study funded by Amgen Inc. PJM has received research grants, consulting fees, and/or speaker honoraria from Amgen Inc. MCG has received research grants and consulting fees from Amgen Inc. AM, HNV, and DC are employees and shareholders of Amgen Inc. JF, NE, and AN are former employees and shareholders of Amgen Inc.

  • Accepted for publication August 31, 2015.

REFERENCES

  1. 1.↵
    1. Gladman DD,
    2. Antoni C,
    3. Mease P,
    4. Clegg DO,
    5. Nash P
    . Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 2005;64 Suppl 2:ii14–7.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    1. Gottlieb A,
    2. Korman NJ,
    3. Gordon KB,
    4. Feldman SR,
    5. Lebwohl M,
    6. Koo JY,
    7. et al.
    Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol 2008;58:851–64.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Lloyd P,
    2. Ryan C,
    3. Menter A
    . Psoriatic arthritis: an update. Arthritis 2012;2012:176298.
    OpenUrlPubMed
  4. 4.↵
    1. Gelfand JM,
    2. Gladman DD,
    3. Mease PJ,
    4. Smith N,
    5. Margolis DJ,
    6. Nijsten T,
    7. et al.
    Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol 2005;53:573.
    OpenUrlPubMed
  5. 5.↵
    1. Mease PJ,
    2. Gladman DD,
    3. Papp KA,
    4. Khraishi MM,
    5. Thaci D,
    6. Behrens F,
    7. et al.
    Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol 2013;69:729–35.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Mease P
    . Psoriatic arthritis and spondyloarthritis assessment and management update. Curr Opin Rheumatol 2013;25:287–96.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Lee S,
    2. Mendelsohn A,
    3. Sarnes E
    . The burden of psoriatic arthritis: a literature review from a global health systems perspective. P T 2010;35:680–9.
    OpenUrlPubMed
  8. 8.↵
    1. Kane D,
    2. Stafford L,
    3. Bresnihan B,
    4. FitzGerald O
    . A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology 2003;42:1460–8.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. McHugh NJ,
    2. Balachrishnan C,
    3. Jones SM
    . Progression of peripheral joint disease in psoriatic arthritis: a 5-yr prospective study. Rheumatology 2003;42:778–83.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Armstrong AW,
    2. Schupp C,
    3. Wu J,
    4. Bebo B
    . Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data 2003–2011. PLoS One 2012;7:e52935.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Wittkowski KM,
    2. Leonardi C,
    3. Gottlieb A,
    4. Menter A,
    5. Krueger GG,
    6. Tebbey PW,
    7. et al.
    Clinical symptoms of skin, nails, and joints manifest independently in patients with concomitant psoriasis and psoriatic arthritis. PLoS One 2011;6:e20279.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Reich K,
    2. Kruger K,
    3. Mossner R,
    4. Augustin M
    . Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective interdisciplinary epidemiological study of 1511 patients with plaque-type psoriasis. Br J Dermatol 2009;160:1040–7.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Rosen CF,
    2. Mussani F,
    3. Chandran V,
    4. Eder L,
    5. Thavaneswaran A,
    6. Gladman DD
    . Patients with psoriatic arthritis have worse quality of life than those with psoriasis alone. Rheumatology 2012;51:571–6.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Ritchlin CT,
    2. Kavanaugh A,
    3. Gladman DD,
    4. Mease PJ,
    5. Helliwell P,
    6. Boehncke WH,
    7. et al.
    Treatment recommendations for psoriatic arthritis. Ann Rheum Dis 2009;68:1387–94.
    OpenUrlAbstract/FREE Full Text
  15. 15.↵
    1. Benham H,
    2. Norris P,
    3. Goodall J,
    4. Wechalekar MD,
    5. FitzGerald O,
    6. Szentpetery A,
    7. et al.
    Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res Ther 2013;15:R136.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Dardalhon V,
    2. Korn T,
    3. Kuchroo VK,
    4. Anderson AC
    . Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun 2008;31:252–6.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Leipe J,
    2. Grunke M,
    3. Dechant C,
    4. Reindl C,
    5. Kerzendorf U,
    6. Schulze-Koops H,
    7. et al.
    Role of Th17 cells in human autoimmune arthritis. Arthritis Rheum 2010;62:2876–85.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Lowes MA,
    2. Kikuchi T,
    3. Fuentes-Duculan J,
    4. Cardinale I,
    5. Zaba LC,
    6. Haider AS,
    7. et al.
    Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 2008;128:1207–11.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Maeda S,
    2. Hayami Y,
    3. Naniwa T,
    4. Ueda R
    . The Th17/IL-23 axis and natural immunity in psoriatic arthritis. Int J Rheumatol 2012;2012:539683.
    OpenUrlPubMed
  20. 20.↵
    1. Shen H,
    2. Goodall JC,
    3. Hill Gaston JS
    . Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 2009;60:1647–56.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Tesmer LA,
    2. Lundy SK,
    3. Sarkar S,
    4. Fox DA
    . Th17 cells in human disease. Immunol Rev 2008;223:87–113.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Langrish CL,
    2. Chen Y,
    3. Blumenschein WM,
    4. Mattson J,
    5. Basham B,
    6. Sedgwick JD,
    7. et al.
    IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005;201:233–40.
    OpenUrlAbstract/FREE Full Text
  23. 23.↵
    1. Park H,
    2. Li Z,
    3. Yang XO,
    4. Chang SH,
    5. Nurieva R,
    6. Wang YH,
    7. et al.
    A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005;6:1133–41.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Kotake S,
    2. Udagawa N,
    3. Takahashi N,
    4. Matsuzaki K,
    5. Itoh K,
    6. Ishiyama S,
    7. et al.
    IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 1999;103:1345–52.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Liang SC,
    2. Long AJ,
    3. Bennett F,
    4. Whitters MJ,
    5. Karim R,
    6. Collins M,
    7. et al.
    An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment. J Immunol 2007;179:7791–9.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Liang SC,
    2. Tan XY,
    3. Luxenberg DP,
    4. Karim R,
    5. Dunussi-Joannopoulos K,
    6. Collins M,
    7. et al.
    Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006;203:2271–9.
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. Jandus C,
    2. Bioley G,
    3. Rivals JP,
    4. Dudler J,
    5. Speiser D,
    6. Romero P
    . Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum 2008;58:2307–17.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Raychaudhuri SP,
    2. Raychaudhuri SK,
    3. Genovese MC
    . IL-17 receptor and its functional significance in psoriatic arthritis. Mol Cell Biochem 2012;359:419–29.
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Papp KA,
    2. Leonardi C,
    3. Menter A,
    4. Ortonne JP,
    5. Krueger JG,
    6. Kricorian G,
    7. et al.
    Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 2012;366:1181–9.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Mease PJ,
    2. Genovese MC,
    3. Greenwald MW,
    4. Ritchlin CT,
    5. Beaulieu AD,
    6. Deodhar A,
    7. et al.
    Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med 2014;370:2295–306.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Bushnell DM,
    2. Martin ML,
    3. McCarrier K,
    4. Gordon K,
    5. Chiou CF,
    6. Huang X,
    7. et al.
    Validation of the Psoriasis Symptom Inventory (PSI), a patient-reported outcome measure to assess psoriasis symptom severity. J Dermatolog Treat 2013;24:356–60.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Mease PJ,
    2. Woolley JM,
    3. Singh A,
    4. Tsuji W,
    5. Dunn M,
    6. Chiou CF
    . Patient-reported outcomes in a randomized trial of etanercept in psoriatic arthritis. J Rheumatol 2010;37:1221–7.
    OpenUrlAbstract/FREE Full Text
  33. 33.↵
    1. Gordon KB,
    2. Kimball AB,
    3. Chau D,
    4. Viswanathan HN,
    5. Li J,
    6. Revicki DA,
    7. et al.
    Impact of brodalumab treatment on psoriasis symptoms and health-related quality of life: use of a novel patient-reported outcome measure, the Psoriasis Symptom Inventory. Br J Dermatol 2014;170:705–15.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Martin ML,
    2. McCarrier KP,
    3. Chiou CF,
    4. Gordon K,
    5. Kimball AB,
    6. Van Voorhees AS,
    7. et al.
    Early development and qualitative evidence of content validity for the Psoriasis Symptom Inventory (PSI), a patient-reported outcome measure of psoriasis symptom severity. J Dermatolog Treat 2013;24:255–60.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Revicki DA,
    2. Jin Y,
    3. Wilson HD,
    4. Chau D,
    5. Viswanathan HN
    . Reliability and validity of the psoriasis symptom inventory in patients with moderate-to-severe psoriasis. J Dermatolog Treat 2014;25:8–14.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Mease PJ,
    2. Genovese MC,
    3. Mutebi A,
    4. Wilson H,
    5. Revicki DA,
    6. Erondu N,
    7. et al.
    Reliability and construct validity of the Psoriasis Symptom Inventory in subjects with psoriatic arthritis. Ann Rheum Dis 2014;73 Suppl2: 1054.
    OpenUrl
  37. 37.↵
    1. Dandorfer SW,
    2. Rech J,
    3. Manger B,
    4. Schett G,
    5. Englbrecht M
    . Differences in the patient’s and the physician’s perspective of disease in psoriatic arthritis. Semin Arthritis Rheum 2012;42:32–41.
    OpenUrlCrossRefPubMed
  38. 38.↵
    1. United States Food and Drug Administration
    . Guidance for industry. Patient-reported outcome measures: use in medical product development to support labeling claims. [Internet. Accessed October 6, 2015.] Available from: www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM193282
  39. 39.↵
    1. Frankel EH,
    2. Strober BE,
    3. Crowley JJ,
    4. Fivenson DP,
    5. Woolley JM,
    6. Yu EB,
    7. et al.
    Etanercept improves psoriatic arthritis patient-reported outcomes: results from EDUCATE. Cutis 2007;79:322–6.
    OpenUrlPubMed
  40. 40.↵
    1. Gladman DD,
    2. Mease PJ,
    3. Krueger G,
    4. van der Heijde DM,
    5. Antoni C,
    6. Helliwell PS,
    7. et al.
    Outcome measures in psoriatic arthritis. J Rheumatol 2005;32:2262–9.
    OpenUrlAbstract/FREE Full Text
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Keywords

PSORIATIC ARTHRITIS
BIOLOGICAL PRODUCTS
PATIENT OUTCOME ASSESSMENT
PSORIASIS

Keywords