Publications by authors named "Joseph F Merola"

161 Publications

Moving the Goalpost Towards Remission: The Case for Combination Immunomodulatory Therapies in Psoriatic Arthritis.

Arthritis Rheumatol 2021 Apr 12. Epub 2021 Apr 12.

Division of Allergy, Immunology and Rheumatology, Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

Following the pivotal manuscript that outlined unique disease features half a century ago, investigators in the field of psoriatic arthritis (PsA) have extrapolated clinical trial data and molecular insights from the more expansive experience in rheumatoid arthritis (RA). As a result, many of the diagnostic approaches, imaging modalities, therapeutics and outcome measures paralleled (and at times became identical to) those developed for RA.
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http://dx.doi.org/10.1002/art.41765DOI Listing
April 2021

The CLASI, a validated tool for the evaluation of skin disease in lupus erythematosus: a narrative review.

Ann Transl Med 2021 Mar;9(5):431

Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.

Cutaneous lupus erythematosus (CLE) can present with or without features of systemic lupus erythematosus (SLE), with estimates of the incidence of isolated skin disease almost equaling the incidence of those with systemic disease. However, despite the impact CLE has on a patient's quality of life (QoL), there has been no US Food and Drug Administration (FDA) approved treatment for the disease in the past 50 years. In addition, patients with skin predominant LE are often excluded from clinical SLE trials. In the rare trials that include patients with skin predominant LE, disease activity and progression in the skin are often difficult to evaluate using multi-organ outcome measures. The need for new therapies for CLE and the lack of focus on skin outcomes has led to the development of the Cutaneous Lupus Disease Area and Severity Index (CLASI), a validated organ-specific outcome measure that is not only responsive to change in disease activity and damage but also correlated to changes in a patient's QoL. This paper will emphasize the extensive validation studies performed in developing the CLASI, as well as the importance of clinical trials using the CLASI to address the need for improved therapies for patients with lupus skin manifestations.
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http://dx.doi.org/10.21037/atm-20-5048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033342PMC
March 2021

Evaluating safety and compatibility of anti-tumor necrosis factor therapy in patients with connective tissue disorders.

Ann Transl Med 2021 Mar;9(5):430

Department of Dermatology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA.

Inhibition of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) has been utilized as a treatment strategy for a variety of immune-mediated inflammatory disorders (IMID), including rheumatoid arthritis, Crohn's disease and psoriasis. A wide array of biologic therapies targeting the TNFα molecule, including etanercept, infliximab, certolizumab, golimumab and adalimumab, are routinely used in the care of patients with these conditions. In addition to their therapeutic potential, anti-TNFα agents commonly induce the formation of autoantibodies such as anti-nuclear antibodies and anti-double stranded DNA antibodies; however, the vast majority of these are of IgM isotype and of unclear clinical significance, uncommonly leading to drug-induced autoimmune disease. For these reasons, TNFα inhibition has been a controversial strategy in the treatment of primary connective tissue disorders (CTDs). However, as new therapeutics continue to be developed for the management of CTDs, the potential utility for anti-TNFα agents has become of great interest, demonstrated in several recent case series and small open-label trials. We review the safety and compatibility of anti-TNFα therapy in the management of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE), two well-studied example CTDs, as well as summarize the risks of autoantibody generation, infection, malignancy, and iatrogenic lupus flares as side effects of blocking TNFα in patients with these conditions.
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http://dx.doi.org/10.21037/atm-20-5552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033307PMC
March 2021

The catch-22 of limited Food and Drug Administration approval for connective tissue disease therapies.

J Am Acad Dermatol 2021 Apr 3. Epub 2021 Apr 3.

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School (Boston, MA). Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.03.103DOI Listing
April 2021

Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis.

N Engl J Med 2021 04;384(13):1227-1239

From the College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (I.B.M.); AbbVie, North Chicago, IL (J.K.A., X.W., L.C., P.Z., J.L., A.L.P.); Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland (M.M.); Brigham and Women's Hospital and Harvard Medical School, Boston (J.F.M.); the Department of Rheumatology, West China Hospital, Sichuan University, Chengdu, China (Y.L.); the Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo (M.K.); the Department of Rheumatology and Connective Tissue Diseases, Collegium Medicum Uniwersytet Mikołaja Kopernika, 2nd University Hospital, Bydgoszcz, Poland (S.J.); Facultad de Medicina, Universidad Autonoma de Chihuahua, Chihuahua, Mexico (C.P.-T.); and Goethe University and Fraunhofer Institute for Molecular Biology and Applied Ecology-Branch for Translational Medicine and Pharmacology and Cluster of Excellence for Immune-Mediated Diseases, Frankfurt, Germany (F.B.).

Background: The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor necrosis factor α inhibitor, in patients who have an inadequate response to nonbiologic disease-modifying antirheumatic drugs are unclear.

Methods: In a 24-week, phase 3 trial, we randomly assigned patients in a 1:1:1:1 ratio to receive oral upadacitinib at a dose of 15 mg or 30 mg once daily, placebo, or subcutaneous adalimumab (40 mg every other week). The primary end point was an American College of Rheumatology 20 (ACR20) response (≥20% decrease in the number of tender and swollen joints and ≥20% improvement in at least three of five other domains) at week 12 with upadacitinib as compared with placebo. Secondary end points included comparisons of upadacitinib with adalimumab.

Results: A total of 1704 patients received an active drug or placebo. The percentage of patients who had an ACR20 response at week 12 was 70.6% with 15-mg upadacitinib, 78.5% with 30-mg upadacitinib, 36.2% with placebo (P<0.001 for both upadacitinib doses vs. placebo), and 65.0% with adalimumab. The difference between groups for 15-mg upadacitinib as compared with adalimumab was 5.6 percentage points (95% confidence interval [CI], -0.6 to 11.8) and for 30-mg upadacitinib as compared with adalimumab was 13.5 percentage points (95% CI, 7.5 to 19.4). Both upadacitinib doses were noninferior to adalimumab for the ACR20 response at week 12; the 30-mg dose but not the 15-mg dose was superior to adalimumab. The incidence of adverse events through week 24 was 66.9% with 15-mg upadacitinib, 72.3% with 30-mg upadacitinib, 59.6% with placebo, and 64.8% with adalimumab. There were serious infections in 1.2%, 2.6%, 0.9%, and 0.7% of the patients, respectively. Hepatic disorders occurred in 9.1% of patients in the 15-mg upadacitinib group and 12.3% in the 30-mg upadacitinib group, but grade 3 increases in aminotransferase levels occurred in 2% of patients or fewer in all groups.

Conclusions: The percentage of patients with psoriatic arthritis who had an ACR20 response at week 12 was significantly higher with 15-mg or 30-mg upadacitinib than with placebo. The 30-mg dose but not the 15-mg dose was superior to adalimumab. Adverse events were more frequent with upadacitinib than with placebo. (Funded by AbbVie; SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400.).
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http://dx.doi.org/10.1056/NEJMoa2022516DOI Listing
April 2021

Tralokinumab Does Not Impact Vaccine-induced Immune Responses: Results From a 30-week, Randomized, Placebo-controlled Trial in Adults With Moderate-to-severe Atopic Dermatitis.

J Am Acad Dermatol 2021 Mar 17. Epub 2021 Mar 17.

Division of Dermatology, University of Alberta, Edmonton, Alberta, Canada.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Interleukin (IL)-13, a type 2 cytokine, is key in AD inflammation. Tralokinumab is a first-in-class, fully human, monoclonal antibody that specifically binds with high affinity and neutralizes IL-13 in AD. Immunomodulatory treatments may impair vaccine-induced immune responses.

Objective: Assess immune responses to standard vaccines in tralokinumab-treated adults with moderate-to-severe AD.

Methods: ECZTRA 5 (NCT03562377) was a phase 2, double-blind, randomized, placebo-controlled, 30-week trial. Eligible adults were randomized 1:1 (tralokinumab 300 mg or placebo, 107:108 every 2 weeks [q2w] for 16 weeks), receiving Tdap (tetanus/diphtheria/pertussis) and meningococcal vaccines at week 12. Primary endpoints were positive anti-tetanus and anti-meningococcal responses (week 12-week 16; noninferiority margin, -25%; responder, >3-fold immunoglobulin-G increase).

Results: At week 16, noninferiority of tralokinumab versus placebo for immune responses to Tdap (91.9% vs 96.1%) and meningococcal (86.0% vs 84.2%) vaccines was demonstrated. During treatment, adverse-event rates were lower for tralokinumab versus placebo; most events were mild or moderate.

Limitations: Responses to other vaccines (including influenza) not examined.

Conclusion: Tralokinumab 300 mg q2w treatment did not affect immune responses to Tdap and meningococcal vaccines, and was well tolerated when administered concomitantly, with safety profile comparable to phase 3 trials.
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http://dx.doi.org/10.1016/j.jaad.2021.03.032DOI Listing
March 2021

Impaired Coronary Vasodilator Reserve and Adverse Prognosis in Patients With Systemic Inflammatory Disorders.

JACC Cardiovasc Imaging 2021 Mar 10. Epub 2021 Mar 10.

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiovascular Imaging Program, Departments of Medicine and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Objectives: The purpose of this study was to evaluate the prognostic value of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR), reflecting the integrated effects of diffuse atherosclerosis and microvascular dysfunction in patients with systemic inflammatory disorders.

Background: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis (PsO) are common inflammatory conditions with excess cardiovascular (CV) risk compared to the general population. Systemic inflammation perturbs endothelial function and has been linked to coronary vasomotor dysfunction. However, the prognostic significance of this vascular dysfunction is not known.

Methods: This was a retrospective study of patients with RA, SLE, and PsO undergoing clinically indicated rest and stress myocardial perfusion positron emission tomography (PET). Patients with an abnormal myocardial perfusion study or left ventricular dysfunction were excluded. MFR was calculated as the ratio of myocardial blood flow (MBF, ml/min/g) at peak stress compared to that at rest.

Results: Among the 198 patients (median age: 65 years; 80% female), 20.7% had SLE, 31.8% had PsO, and 47.5% had RA. There were no differences in mean MFR between these conditions. Over a median follow-up of 7.8 years, there were 51 deaths and 63 major adverse cardiovascular events (MACE). Patients in the lowest tertile (MFR <1.65) had higher all-cause mortality than the highest tertile, which remained significant after adjusting for age, sex, and the pre-test clinical risk score (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.05 to 5.4; p = 0.038). Similarly, compared to the highest MFR tertile, those in the lowest tertile had a lower MACE-free survival after adjusting for age, sex, and the pre-test clinical risk score (HR: 3.6; 95% CI: 1.7 to 7.6; p = 0.001).

Conclusions: In patients with systemic inflammatory disorders, impaired coronary vasodilator reserve was associated with worse cardiovascular outcomes and all-cause mortality.
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http://dx.doi.org/10.1016/j.jcmg.2020.12.031DOI Listing
March 2021

Psoriasis and Psoriatic Arthritis in the Context of the COVID-19 Pandemic: A Plenary Session From the GRAPPA 2020 Annual Meeting.

J Rheumatol 2021 Mar 15. Epub 2021 Mar 15.

As part of the supplement series GRAPPA 2020, this report was reviewed internally and approved by the Guest Editors for integrity, accuracy, and consistency with scientific and ethical standards. RH has received funding from the National Psoriasis Foundation, NIH/ NIAMS T32AR069515, The Riley Family Foundation, The Snyder Family Foundation, Bloomberg Philanthropies Covid-19 Response Initiative Grant, and the Rheumatology Research Foundation. 1P.J. Mease, MD, MACR, Rheumatology Research, Swedish Medical Center/ Providence St. Joseph Health and University of Washington School of Medicine, Seattle, Washington; 2L.H. Calabrese, DO, Professor of Medicine, Cleveland Clinic Lerner College of Medicine, RJ Fasenmyer Chair of Clinical Immunology, Cleveland Clinic, Cleveland, Ohio; 3K. Callis Duffin, MD, MS, Professor and Chair, Department of Dermatology, University of Utah, Salt Lake City, Utah; 4R. Haberman, MD, MSCI, Clinical Instructor, Department of Medicine, Division of Rheumatology, NYU Grossman School of Medicine, New York, New York; 5R. Firmino, GRAPPA Patient Research Partner; 6J.U. Scher, MD, Department of Medicine, NYU Grossman School of Medicine, New York, New York; 7L. Schick, GRAPPA Patient Research Partner; 8K. Winthrop, MD, MPH, Oregon Health & Science University- Portland State University School of Public Health, Portland, Oregon; 9J.F. Merola, MD, MMSc, Harvard Medical School, Brigham and Women's Hospital, Department of Dermatology and Department of Medicine, Division of Rheumatology and Immunology, Boston, Massachusetts, USA. The authors report the following conflicts of interest: PJM with AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, SUN Pharma, and UCB; KCD with Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Bristol Myers Squibb, Stiefel, Novartis, Pfizer, Sienna, UCB, Regeneron, Boehringer Ingelheim, and Ortho Dermatologic; RH with Janssen; JUS with AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, and UCB; KW with Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Regeneron, Sanofi, AstraZeneca, Novartis, and BMS; JFM with Merck, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres, and Leo Pharma. LHC, LS, and RF declare no conflicts. Address correspondence to Dr. P.J. Mease, Rheumatology Research, Swedish Medical Center/Providence St. Joseph Health, Seattle, WA 98122, USA. Email:

The coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic has affected the healthcare system on a global scale, and we utilized the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 annual meeting to examine how COVID-19 might affect patients with psoriatic disease (PsD) and the clinicians who care for them. Pressing issues and concerns identified included whether having psoriasis increased the risk of acquiring COVID-19, vaccine safety, and the acceptability of telehealth. The general message from rheumatologists, dermatologists, infectious disease specialists, and patient research partners was that data did not suggest that having PsD or its treatment significantly increased risk of infection or more severe disease course, and that the telehealth experience was a success overall.
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http://dx.doi.org/10.3899/jrheum.201671DOI Listing
March 2021

Report of the Skin Research Working Groups From the GRAPPA 2020 Annual Meeting.

J Rheumatol 2021 Mar 15. Epub 2021 Mar 15.

As part of the supplement series GRAPPA 2020, this report was reviewed internally and approved by the Guest Editors for integrity, accuracy, and consistency with scientific and ethical standards. L.M. Perez-Chada, MD, MMSc, Department of Dermatology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA; A. Kohn, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida, USA; A.B. Gottlieb, MD, PhD, Department of Dermatology, Icahn School of Medicine at Mt Sinai, New York, New York, USA; A.W. Armstrong, MD, MPH, Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA; L. Eder, MD, PhD, Assistant Professor of Medicine, University of Toronto and Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada; P.J. Mease, MD, Swedish Medical Center/Providence St Joseph Health and University of Washington School of Medicine, Seattle, Washington, USA; A. Ogdie, MD, MSCE, Department of Medicine/Division of Rheumatology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; V. Strand, MD, Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, California, USA; J.F. Merola, MD, MMSc, Derpartment of Dermatology, and Department of Medicine, Division of Rheumatology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA. This paper does not require institutional review board approval. Address correspondence to Dr. J.F. Merola, Department of Dermatology and Medicine, Division of Rheumatology, Harvard Medical School, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115, USA. Email:

At the 2020 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the International Dermatology Outcome Measures (IDEOM) Initiative Psoriasis (PsO) Working Group presented an update on its work to agree on meaningful, valid, and feasible outcome measures for PsO randomized controlled trials and longitudinal observational studies. The Treatment Satisfaction Working Group presented the development of a treatment satisfaction instrument to be utilized in PsO clinical trials. The Musculoskeletal Symptoms Working Group presented an overview of their work conducted to date to define how to best measure musculoskeletal symptoms in PsO clinical studies, and discussed next steps during an open-panel discussion, which included PsO and psoriatic arthritis experts.
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http://dx.doi.org/10.3899/jrheum.201668DOI Listing
March 2021

Validation of claims-based algorithms to identify patients with psoriasis.

Pharmacoepidemiol Drug Saf 2021 Mar 13. Epub 2021 Mar 13.

Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Purpose: Accurately identifying patients with psoriasis (PsO) is crucial for generating real-world evidence on PsO disease course and treatment utilization.

Methods: We developed nine claims-based algorithms for PsO using a combination of the International Classification of Diseases (ICD)-9 codes, specialist visit, and medication dispensing using Medicare linked to electronic health records data (2013-2014) in two healthcare provider networks in Boston, Massachusetts. We calculated positive predictive value (PPV) and 95% confidence interval (CI) for each algorithm using the treating physician's diagnosis of PsO via chart review as the gold standard. Among the confirmed PsO cases, we assessed their PsO disease activity.

Results: The nine claims-based algorithms identified 990 unique patient records. Of those, 918 (92.7%) with adequate information were reviewed. The PPV of the algorithms ranged from 65.1 to 82.9%. An algorithm defined as ≥1 ICD-9 diagnosis code for PsO and ≥1 prescription claim for topical vitamin D agents showed the highest PPV (82.9%). The PPV of the algorithm requiring ≥2 ICD-9 diagnosis codes and ≥1 prescription claim for PsO treatment excluding topical steroids was 81.1% but higher (82.5%) when ≥1 diagnosis was from a dermatologist. Among 411 PsO patients with adequate information on PsO disease activity in EHRs, 1.5-5.8% had no disease activity, 31.3-36.8% mild, and 26.9-35.1% moderate-to-severe across the algorithms.

Conclusions: Claims-based algorithms based on a combination of PsO diagnosis codes and dispensing for PsO-specific treatments had a moderate-to-high PPV. These algorithms can serve as a useful tool to identify patients with PsO in future real-world data pharmacoepidemiologic studies.
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http://dx.doi.org/10.1002/pds.5229DOI Listing
March 2021

Clinical implications and predictive values of early PASI responses to tildrakizumab in patients with moderate-to-severe plaque psoriasis.

J Dermatolog Treat 2021 Mar 18:1-6. Epub 2021 Mar 18.

Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Objective: To evaluate whether early Psoriasis Area Severity Index (PASI) improvements can predict week 28 tildrakizumab responders and nonresponders.

Methods: Psoriasis patients pooled from two tildrakizumab phase 3 trials randomized to receive tildrakizumab 100 mg at weeks 0, 4, 16, and 28 were included. Patients were grouped by week 28 PASI responses (<50, 50-74, 75-89, and 90-100). PASI improvements from baseline at weeks 4 and 16 were analyzed for each response group.

Results: Of 575 patients included, 8.3%, 14.3%, 23.8%, and 53.6%, respectively, achieved PASI <50, 50-74, 75-89, and 90-100 at week 28. Of patients with PASI <50 at week 16, 85% did not achieve PASI ≥75 at week 28 (nonresponders). Rapid response, defined as PASI ≥50 at week 4 (after a single tildrakizumab dose), was observed in 41% of patients. Of these patients, 87% were week 28 responders (PASI ≥75); 67% were 'super responders' (PASI 90-100). Among week 28 responders and super responders, 45% and 50% achieved PASI ≥50 at week 4, respectively.

Conclusions: Tildrakizumab week 28 nonresponders can be identified by week 16 PASI response. PASI improvements as early as week 4 can predict patients' week 28 PASI improvement status.
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http://dx.doi.org/10.1080/09546634.2021.1898528DOI Listing
March 2021

RNA tape sampling in cutaneous lupus erythematosus discriminates affected from unaffected and healthy volunteer skin.

Lupus Sci Med 2021 03;8(1)

Biogen Inc, Cambridge, Massachusetts, USA

Objective: Punch biopsy, a standard diagnostic procedure for patients with cutaneous lupus erythematosus (CLE) carries an infection risk, is invasive, uncomfortable and potentially scarring, and impedes patient recruitment in clinical trials. Non-invasive tape sampling is an alternative that could enable serial evaluation of specific lesions. This cross-sectional pilot research study evaluated the use of a non-invasive adhesive tape device to collect messenger RNA (mRNA) from the skin surface of participants with CLE and healthy volunteers (HVs) and investigated its feasibility to detect biologically meaningful differences between samples collected from participants with CLE and samples from HVs.

Methods: Affected and unaffected skin tape samples and simultaneous punch biopsies were collected from 10 participants with CLE. Unaffected skin tape and punch biopsies were collected from 10 HVs. Paired samples were tested using quantitative PCR for a candidate immune gene panel and semi-quantitative immunohistochemistry for hallmark CLE proteins.

Results: mRNA collected using the tape device was of sufficient quality for amplification of 94 candidate immune genes. Among these, we found an interferon (IFN)-dominant gene cluster that differentiated CLE-affected from HV (23-fold change; p<0.001) and CLE-unaffected skin (sevenfold change; p=0.002), respectively. We found a CLE-associated gene cluster that differentiated CLE-affected from HV (fourfold change; p=0.005) and CLE-unaffected skin (fourfold change; p=0.012), respectively. Spearman's correlation between per cent area myxovirus 1 protein immunoreactivity and IFN-dominant mRNA gene cluster expression was highly significant (dermis, rho=0.86, p<0.001). In total, skin tape-derived RNA expression comprising both IFN-dominant and CLE-associated gene clusters correlated with per cent area immunoreactivity of some hallmark CLE-associated proteins in punch biopsies from the same lesions.

Conclusions: A non-invasive tape RNA collection technique is a potential tool for repeated skin biomarker measures throughout a clinical trial.
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http://dx.doi.org/10.1136/lupus-2020-000428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931768PMC
March 2021

Consensus terminology for preclinical phases of psoriatic arthritis for use in research studies: results from a Delphi consensus study.

Nat Rev Rheumatol 2021 Apr 15;17(4):238-243. Epub 2021 Feb 15.

Department of Medicine, Division of Rheumatology, New York University Langone Health, New York, NY, USA.

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: 'increased risk for PsA', 'psoriasis with asymptomatic synovio-entheseal imaging abnormalities' and 'psoriasis with musculoskeletal symptoms not explained by other diagnosis'. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated.
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http://dx.doi.org/10.1038/s41584-021-00578-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997804PMC
April 2021

Seroconversion of severe acute respiratory syndrome coronavirus 2-infected patients on immunosuppression: A retrospective analysis.

J Am Acad Dermatol 2021 Feb 4. Epub 2021 Feb 4.

Department of Dermatology at Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.01.100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860940PMC
February 2021

Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial.

Lancet 2021 Feb;397(10273):487-498

Icahn School of Medicine, New York, NY, USA.

Background: There is an unmet need for a treatment for psoriasis that results in complete skin clearance with a reliably quick response. Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. We aimed to compare the efficacy and safety of bimekizumab with placebo and ustekinumab in patients with moderate to severe plaque psoriasis over 52 weeks.

Methods: BE VIVID was a multicentre, randomised, double-blind, active comparator and placebo controlled phase 3 trial done across 105 sites (clinics, hospitals, research units, and private practices) in 11 countries in Asia, Australia, Europe, and North America. Adults aged 18 years or older with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥12, ≥10% body surface area affected by psoriasis, and Investigator's Global Assessment [IGA] score ≥3 on a five point scale) were included. Randomisation was stratified by geographical region and previous exposure to biologics; patients, investigators, and sponsors were masked to treatment assignment. Patients were randomly assigned (4:2:1) using an interactive response technology to bimekizumab 320 mg every 4 weeks, ustekinumab 45 mg or 90 mg (baseline weight-dependent dosing) at weeks 0 and 4, then every 12 weeks, or placebo every 4 weeks. At week 16, patients receiving placebo switched to bimekizumab 320 mg every 4 weeks. All study treatments were administered as two subcutaneous injections. Coprimary endpoints were the proportion of patients with 90% improvement in the PASI (PASI90) and the proportion of patients with an IGA response of clear or almost clear (score 0 or 1) at week 16 (non-responder imputation). Efficacy analyses included the intention-to-treat population; safety analysis included patients who received at least one dose of study treatment. This trial was registered at ClinicalTrials.gov, NCT03370133 (completed).

Findings: Between Dec 6, 2017, and Dec 13, 2019, 735 patients were screened and 567 were enrolled and randomly assigned (bimekizumab 320 mg every 4 weeks n=321, ustekinumab 45 mg or 90 mg every 12 weeks n=163, placebo n=83). At week 16, 273 (85%) of 321 patients in the bimekizumab group had PASI90 versus 81 (50%) of 163 in the ustekinumab group (risk difference 35 [95% CI 27-43]; p<0·0001) and four (5%) of 83 in the placebo group (risk difference 80 [74-86]; p<0·0001). At week 16, 270 (84%) patients in the bimekizumab group had an IGA response versus 87 (53%) in the ustekinumab group (risk difference 30 [95% CI 22-39]; p<0·0001) and four (5%) in the placebo group (risk difference 79 [73-85]; p<0·0001). Over 52 weeks, serious treatment-emergent adverse events were reported in 24 (6%) of 395 patients in the bimekizumab group (including those who switched from placebo at week 16) and 13 (8%) of 163 in the ustekinumab group.

Interpretation: Bimekizumab was more efficacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. The bimekizumab safety profile was consistent with that observed in previous studies.

Funding: UCB Pharma.
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http://dx.doi.org/10.1016/S0140-6736(21)00125-2DOI Listing
February 2021

Correction to: Pseudovasculitis: an etiology not to miss.

Clin Rheumatol 2021 Feb 1. Epub 2021 Feb 1.

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA, USA.

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http://dx.doi.org/10.1007/s10067-021-05615-9DOI Listing
February 2021

Characteristics of Patients with Psoriasis Treated with Apremilast in the Corrona Psoriasis Registry.

Dermatol Ther (Heidelb) 2021 Feb 21;11(1):253-263. Epub 2021 Jan 21.

Yale University, New Haven, CT, USA.

Introduction: Data on the characteristics of apremilast patients in real-world settings are limited. We assessed the demographics and disease characteristics of apremilast-treated patients in the Corrona Psoriasis Registry overall and by treatment history.

Methods: The Corrona Psoriasis Registry is a large, independent, prospective, observational registry of adult patients (age ≥ 18 years) who initiate an eligible systemic medication for treatment of psoriasis at or after enrollment (incident users) or within 12 months before enrollment (prevalent users). The current analyses included psoriasis patients enrolled in the Corrona Psoriasis Registry between April 1, 2015, and January 7, 2018. Patients were adults (age ≥ 18 years) with psoriasis who were enrolled between April 1, 2015, and January 7, 2018 and initiated apremilast at the time of registry enrollment or a subsequent visit (incident users) or within the 12 months prior to registry enrollment (prevalent users). Patient characteristics were evaluated descriptively at the index date, defined as the enrollment date for prevalent users and the visit when apremilast was initiated for incident users.

Results: Among 660 patients who initiated apremilast at registry enrollment or a visit thereafter, psoriatic arthritis, hypertension, and hyperlipidemia were common. There were more systemic-experienced (61.4%) versus systemic-naive (38.6%) patients; 43.8% had prior biologic exposure. Most patients were not receiving concomitant systemic treatment (70.2%); 27.4% were receiving concomitant biologic therapy. Most patients had mild or moderate disease (psoriasis-involved body surface area ≤ 10% [76.0%], Investigator Global Assessment ≤ 3 [88.3%], Psoriasis Area and Severity Index ≤ 10 [84.5%]). Dermatologist-reported psoriatic arthritis was present in 47.0% of patients; 33.9% of patients had a Psoriasis Epidemiology Screening Tool score  of ≥ 3, suggestive of psoriatic arthritis. Systemic-experienced apremilast patients had higher rates of obesity and comorbidities and experienced a greater impact on quality of life (mean Dermatology Life Quality Index, 7.3 vs. 6.5) versus systemic-naive patients.

Conclusion: In this real-world observational study of apremilast users in the Corrona Psoriasis Registry, most patients had less-severe disease and higher rates of prior exposure to biologic treatments compared with patients with moderate-to-severe psoriasis enrolled in phase 3 clinical studies.
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http://dx.doi.org/10.1007/s13555-020-00479-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858993PMC
February 2021

Pseudovasculitis: an etiology not to miss.

Clin Rheumatol 2021 Jan 16. Epub 2021 Jan 16.

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA, USA.

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http://dx.doi.org/10.1007/s10067-020-05548-9DOI Listing
January 2021

Patient-reported outcomes data in patients with psoriatic arthritis from a randomised trial of etanercept and methotrexate as monotherapy or in combination.

RMD Open 2021 Jan;7(1)

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Objectives: We examined patient-reported outcomes (PROs) in The Study of Etanercept And Methotrexate in Patients with Psoriatic Arthritis (PsA); a 48-week, phase 3, randomised controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept monotherapy, and MTX+ etanercept in patients with PsA.

Methods: Efficacy endpoints included: mean changes from baseline and proportion of patients who reported improvements≥minimal clinically important difference (MCID) at week 24 in treatment groups for Health Assessment Questionnaire-Disability Index, Patient Global Assessment (PtGA), Patient Global Assessment of Joint Pain (PtGAJP) and Medical Outcomes Study Short Form-36 Questionnaire (SF-36) Physical Component Summary (PCS), and Mental Component Summary, and eight domain scores. PROs were analysed as reported (observed), without multiplicity adjustment; therefore, p values are descriptive.

Results: At week 24, patients receiving etanercept monotherapy or MTX+ etanercept combination reported greater improvements (p≤0.05) in PtGA, PtGAJP and SF-36 PCS scores compared with those receiving MTX monotherapy. Compared with MTX monotherapy, higher proportions of patients receiving etanercept monotherapy and combination therapy reported improvements≥MCID in PtGA (etanercept vs MTX, p=0.005) and PtGAJP (MTX +etanercept vs MTX, p=0.038). Across PROs, proportions of patients reporting scores≥age and gender-matched normative values at week 24 ranged from 20.8% to 51.0% with MTX monotherapy, 30.9% to 48.8% with etanercept monotherapy, and 30.6% to 52.3% with MTX+ etanercept combination.

Conclusions: Patients receiving etanercept monotherapy or MTX+ etanercept reported greater improvements from baseline in several PROs compared with those receiving MTX monotherapy. PROs should be incorporated in discussions between patients and clinicians regarding their treatment choices as they can help determine which treatments are more beneficial in patients with PsA.
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http://dx.doi.org/10.1136/rmdopen-2020-001484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813325PMC
January 2021

National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: Version 2-Advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments.

J Am Acad Dermatol 2021 Jan 7. Epub 2021 Jan 7.

Division of Allergy, Immunology, and Rheumatology Division, University of Rochester Medical Center, Rochester, New York.

Objective: To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic.

Study Design: The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted.

Results: The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus.

Limitations: The evidence behind many guidance statements is variable in quality and/or quantity.

Conclusions: These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge.
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http://dx.doi.org/10.1016/j.jaad.2020.12.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788316PMC
January 2021

De novo cutaneous connective tissue disease temporally associated with immune checkpoint inhibitor therapy: A retrospective analysis.

J Am Acad Dermatol 2021 Mar 24;84(3):864-869. Epub 2020 Oct 24.

Harvard Medical School, Boston, MA; Department of Dermatology, Brigham and Women's Hospital, Boston, MA; Center for Cutaneous Oncology, Department of Dermatology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.10.054DOI Listing
March 2021

Measuring fatigue: a meta-review.

Int J Dermatol 2020 Dec 10. Epub 2020 Dec 10.

Department of Dermatology, Mayo Clinic, Rochester, MN, USA.

There is a lack of validated tools to measure fatigue in patients with inflammatory skin, neuropsychiatric, and medical disorders. The use of nonvalidated tools may compromise the quality of data. The purpose of this meta-review was to evaluate existing fatigue scales commonly used to assess fatigue in other inflammatory conditions and to identify if there are scales that have been validated in dermatologic conditions. The PubMed/MEDLINE and SCOPUS databases were systematically searched from inception through March 10, 2020, in accordance with the PRISMA statement. Validated tools were identified and assessed according to their main measurement properties. The literature search identified 403 references, and eight studies were eligible and assessed in this review. The unidimensional fatigue scales included were the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F), Brief Fatigue Inventory, Fatigue Severity Scale, Numerical Rating Scale - Fatigue, and Visual Analog Scale - Fatigue. The multidimensional fatigue scales found were the Checklist Individual Strength, Chalder Fatigue Scale, Multidimensional Assessment of Fatigue, Multidimensional Fatigue Inventory Scale, and Piper Fatigue Scale. To measure fatigue, a brief scale with the ability to detect change is needed as there is a growing interest in evaluating this dimension of treatment response. In addition, a good content validity is also needed. From this systematic review, none of the selected scales have had content validation, even though the FACIT was validated in patients with psoriatic arthritis. Validation studies in specific disorders are urgently warranted.
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http://dx.doi.org/10.1111/ijd.15341DOI Listing
December 2020

Report from the International Dermatology Outcome Measures Initiative.

J Investig Dermatol Symp Proc 2020 11;20(1):S80-S83

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address:

The International Dermatology Outcome Measures is a nonprofit organization dedicated to developing evidence-based, patient-centered outcome measures for dermatologic conditions. At the 2018 Alopecia Areata Research Summit, Dr Gottlieb, President of the International Dermatology Outcome Measures, presented an overview of their work in psoriasis, hidradenitis suppurativa, acne, and eczema and discussed the potential areas of mutual interest with the National Alopecia Areata Foundation. Herein, we present a summary of the topics discussed.
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http://dx.doi.org/10.1016/j.jisp.2020.05.004DOI Listing
November 2020

Dupilumab and the risk of conjunctivitis and serious infection in patients with atopic dermatitis: A propensity score-matched cohort study.

J Am Acad Dermatol 2021 Feb 7;84(2):300-311. Epub 2020 Oct 7.

Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, Massachusetts.

Background: Dupilumab is an effective treatment for moderate to severe atopic dermatitis (AD) with limited safety data in clinical practice.

Objective: To assess the 6-month risk of conjunctivitis and serious infections in patients with AD who initiated dupilumab.

Methods: In a cohort study using US claims data, we compared the risk of conjunctivitis and serious infections in patients with AD who initiated either dupilumab, methotrexate (MTX), cyclosporine, or mycophenolate. Relative risks (RRs) were computed after 1:1 propensity score matching.

Results: We identified 1775 dupilumab, 1034 MTX, 186 cyclosporine, and 257 mycophenolate users. The 6-month risk for any conjunctivitis was 6.5% for dupilumab, 3.3% for MTX, 4.8% for cyclosporine, and 1.2% for mycophenolate initiators. After PS matching, the RR of any conjunctivitis was increased in dupilumab users versus MTX (RR, 2.45; 95% confidence interval [CI], 1.47-4.08), versus cyclosporine (RR, 1.56; 95% CI, 0.69-3.50), and versus mycophenolate (RR, 7.00; 95% CI, 2.12-23.2). The risk of serious infection was 0.6% in dupilumab and 1.0% in MTX initiators (RR, 0.90; 95% CI, 0.37-2.20).

Limitations: Analyses were based on few events, and differential surveillance is a concern.

Conclusions: Although dupilumab shows a low risk of serious infections, it is associated with a clinically meaningful increase in conjunctivitis that needs to be managed in practice.
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http://dx.doi.org/10.1016/j.jaad.2020.09.084DOI Listing
February 2021

Aiming for Cure and Preventive Initiatives in Psoriatic Disease: Building Synergy at NPF, GRAPPA, and PPACMAN.

Curr Rheumatol Rep 2020 Sep 21;22(11):78. Epub 2020 Sep 21.

Department of Medicine, Division of Rheumatology, NYU Grossman School of Medicine, New York University School of Medicine and NYU Langone Orthopedic Hospital, New York, NY, USA.

Purpose Of Review: To provide a general overview of the organizations dedicated to advance clinical and translational research in the field of psoriatic disease and to describe the current and future opportunities for team science approaches to overcome unmet needs in the field. Descriptions of initiatives from the NPF, PPACMAN, and GRAPPA are summarized.

Recent Findings: Program projects have recently identified areas of knowledge gaps in diagnosis, treatment, and prevention of psoriasis and psoriatic arthritis (PsA). NPF's Psoriasis Prevention Initiative aims to identify interventions that can prevent the onset and relapse of psoriatic disease or related comorbidities. The Psorcast Study is a joint venture between PPACMAN and Sage Bionetworks based on patient-generated smartphone measurements of psoriatic disease. Similarly, GRAPPA is involved in a number of projects related to axial PsA, enthesitis prevalence, and biomarker discoveries. As important initiatives bring new targets for diagnosis and therapeutics in psoriatic disease, supra-endeavors such as the NIH-Accelerating Medicines Partnership (AMP) and the European Innovative Medicines Initiative (IMI) are promising public-private partnerships that can significantly catapult the field forward.
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http://dx.doi.org/10.1007/s11926-020-00958-9DOI Listing
September 2020

National Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1.

J Am Acad Dermatol 2020 Dec 4;83(6):1704-1716. Epub 2020 Sep 4.

Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York.

Objective: To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic.

Study Design: A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted.

Results: The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus.

Limitations: The evidence behind many guidance statements is limited in quality.

Conclusion: These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge.
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http://dx.doi.org/10.1016/j.jaad.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471802PMC
December 2020

Performance of composite measures used in a trial of etanercept and methotrexate as monotherapy or in combination in psoriatic arthritis.

Rheumatology (Oxford) 2021 Mar;60(3):1137-1147

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.

Objectives: To examine which composite measures are most sensitive to change when measuring psoriatic arthritis (PsA) disease activity, analyses compared the responsiveness of composite measures used in a 48-week randomized, controlled trial of MTX and etanercept in patients with PsA.

Methods: The trial randomised 851 patients to receive weekly: MTX (20 mg/week), etanercept (50 mg/week) or MTX plus etanercept. Dichotomous composite measures examined included ACR 20/50/70 responses, minimal disease activity (MDA) and very low disease activity (VLDA). Continuous composite measures examined included Disease Activity Score (28 joints) using CRP (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS).

Results: At week 24, etanercept-treated groups were significantly more effective than MTX monotherapy to achieve ACR 20 (primary end point) and MDA (key secondary end point). When examining score changes from baseline at week 24 across the five continuous composite measures, PASDAS demonstrated relatively greater changes in the etanercept-treated groups compared with MTX monotherapy and had the largest effect size and standardized response. Joint count changes drove overall score changes at week 24 from baseline in all the continuous composite measures except for PASDAS, which was driven by the Physician and Patient Global Assessments.

Conclusion: PASDAS was the most sensitive continuous composite measure examined with results that mirrored the protocol-defined primary and key secondary outcomes. Composite measures with multiple domains, such as PASDAS, may better quantify change in PsA disease burden.

Trail Registration: https://ClinicalTrials.gov, number NCT02376790.
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http://dx.doi.org/10.1093/rheumatology/keaa271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937022PMC
March 2021

Nail Psoriasis Does Not Affect Skin Response to Ixekizumab in Patients With Moderate-To-Severe Psoriasis.

J Drugs Dermatol 2020 Aug;19(8):741-746

Background: Presence of nail psoriasis in patients with plaque psoriasis may be an indicator of greater disease severity. Previously, patients with nail psoriasis have had delayed skin clearance after treatment compared to patients without nail psoriasis. Objective: This post-hoc analysis evaluated the efficacy of ixekizumab in clearance of plaque psoriasis in patients with and without nail psoriasis. Methods: Data were integrated from two phase 3 clinical trials (UNCOVER-2 and UNCOVER-3; N=2570) to assess skin response over 12 weeks of treatment with subcutaneous placebo, etanercept, or ixekizumab in patients with and without nail psoriasis. Nail response was assessed using Nail Psoriasis Severity Index (NAPSI) and skin response was assessed as the percentage of patients achieving 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90, PASI 100) or a score of 0 or 1 on the static Physician Global Assessment (sPGA 0 or 0,1). Results: From baseline to week 12, progressive improvement in psoriasis occurred with ixekizumab and etanercept treatment; however, significantly more patients with nail psoriasis than without mild PASI 75 at weeks 8 and 12 and sPGA (0,1) at week 12 with ixekizumab. Significantly more patients with severe nail psoriasis than mild achieved PASI 75 at weeks 8 and 12 with ixekizumab. Conclusion: Patients with and without nail psoriasis responded well to ixekizumab. The presence of nail psoriasis did not negatively affect skin clearance in patients treated with ixekizumab. ClinicalTrials.gov: NCT01597245, NCT01646177 J Drugs Dermatol. 2020;19(8):741-746. doi:10.36849/JDD.2020.5116.
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http://dx.doi.org/10.36849/JDD.2020.5116DOI Listing
August 2020