Publications by authors named "Alice Gottlieb"

357 Publications

International Dermatology Outcome Measures (IDEOM): Report from the 2020 Annual Meeting.

Dermatology 2021 Sep 17:1-8. Epub 2021 Sep 17.

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

Background: The International Dermatology Outcome Measures (IDEOM) initiative is a non-profit organization that aims to develop evidence-based outcome measurements to evaluate the impact of treatments for patients with dermatological disease. IDEOM includes all key stakeholders in dermatology (patient, physician, industry, insurer, and government) during the process of developing such outcome measurements.

Summary: Here, we provide an update of IDEOM activities that were presented at the 2020 IDEOM Virtual Annual Meeting (October 23-24, 2020). During the meeting, multiple IDEOM workgroups (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) shared their progress to date, as well as future directions in developing and validating Patient-Reported Outcome Measures. Updates on demonstrating efficacy in clinicals trials by the US Food and Drug Administration are also summarized. Key Messages: In this report, we summarize the work presented by each IDEOM workgroup (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) at the 2020 IDEOM Virtual Annual Meeting.
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http://dx.doi.org/10.1159/000518966DOI Listing
September 2021

Psychometric Validation of the Psoriasis Symptoms and Impacts Measure (P-SIM): A Novel Patient-Reported Outcome Instrument for Patients with Plaque Psoriasis, Using Reported Data from the BE RADIANT Phase 3b Trial.

Adv Ther 2021 Sep 2. Epub 2021 Sep 2.

UCB Pharma, Colombes, France.

Introduction: This analysis assessed the psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), a novel patient-reported outcome (PRO) tool designed to capture patient experiences of the signs, symptoms and impacts of psoriasis.

Methods: Blinded data from the BE RADIANT phase 3b trial of bimekizumab were analysed. In BE RADIANT, patients were randomised 1:1 to bimekizumab 320 mg every 4 weeks (Q4W) or secukinumab 300 mg (weekly until Week 4, then Q4W). Three items (itching, skin pain and scaling) of the P-SIM were electronically assessed throughout the trial and were scored from 0 to 10 (none to very severe signs/symptoms/impacts). Test-retest reliability was determined using intraclass correlations. Convergent validity was assessed between P-SIM and other relevant PRO and clinician-reported outcome (ClinRO) scores. Known-groups validity was assessed by comparing mean P-SIM item scores between patient subgroups based on the Psoriasis Area and Severity Index (PASI)/Investigator's Global Assessment (IGA) scores. Responsiveness was assessed via correlations between changes from baseline in P-SIM item scores and other relevant PRO and ClinRO scores. Anchor-based responder analyses and empirical cumulative distribution function (eCDF) curves determined responder thresholds.

Results: The three P-SIM items yielded high intraclass coefficients (> 0.70). By Week 48, the three P-SIM items had moderate (> 0.30 and ≤ 0.50) to strong (> 0.50) correlations with other PROs and weaker correlations with ClinROs, demonstrating good convergent validity. For almost all known-group comparisons, statistically significant between-subgroup score differences were seen across all three P-SIM items. Changes from baseline in the P-SIM and other relevant outcomes were above the acceptable threshold of ≤ 0.30, demonstrating sensitivity to change. Anchor-based analyses determined a ≥ four-point reduction from baseline to indicate marked clinically meaningful improvement for the P-SIM.

Conclusion: These results support the validity, reliability and sensitivity to change of the P-SIM in assessing key symptoms (itching, skin pain and scaling) in patients with moderate to severe plaque psoriasis.

Trial Registration: NCT03536884.
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http://dx.doi.org/10.1007/s12325-021-01836-1DOI Listing
September 2021

Psychometric Validation of the Psoriasis Symptoms and Impacts Measure (P-SIM), a Novel Patient-Reported Outcome Instrument for Patients with Plaque Psoriasis, Using Data from the BE VIVID and BE READY Phase 3 Trials.

Dermatol Ther (Heidelb) 2021 07 14. Epub 2021 Jul 14.

UCB Pharma, Colombes, France.

Introduction: Plaque psoriasis can significantly impact patients' quality of life. We assessed psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), developed to capture patients' experiences of signs, symptoms and impacts of psoriasis.

Methods: Pooled, blinded, 16-week data from 1002 patients in the BE VIVID and BE READY bimekizumab phase 3 trials were analysed. The suitability of the P-SIM missing score rule (weekly scores considered missing if ≥ 4 daily scores were missing) was assessed. Test-retest reliability was evaluated using intraclass correlation coefficients (ICCs). Convergent validity was assessed between P-SIM and relevant patient-reported outcome (PRO) (Dermatology Life Quality Index [DLQI], DLQI item 1 [skin symptoms], Patient Global Assessment of Psoriasis) and clinician-reported outcome (ClinRO) scores (Psoriasis Area and Severity Index [PASI], Investigator's Global Assessment [IGA]) at baseline and week 16. Known-groups validity was assessed, comparing P-SIM scores between patient subgroups predefined using PASI/IGA scores. Sensitivity to change over 16 weeks was evaluated; responder definition (RD) thresholds were explored.

Results: The missing score rule used did not impact P-SIM scores. Test-retest reliability analyses demonstrated excellent score reproducibility (ICC 0.91-0.98). Inter-item correlations at baseline and week 16 were strong (> 0.5), apart from "choice of clothing" with "skin pain" and "burning" at baseline (both 0.49). All P-SIM scores were moderately to strongly correlated with other outcomes, demonstrating convergent validity, apart from ClinROs (PASI, IGA) at baseline that had low variability. P-SIM scores discriminated known groups at week 16, confirming known-groups validity. Changes from baseline to week 16 in P-SIM and other clinically relevant outcomes were strongly correlated (> 0.5; weaker with ClinROs), establishing sensitivity to change. Anchor-based RD analyses determined a four-point P-SIM item score decrease as indicative of marked clinically meaningful improvement.

Conclusion: P-SIM scores demonstrated good reliability, validity and sensitivity to change. A four-point RD threshold could be used to assess 16-week treatment effects.

Trial Registration: BE VIVID: NCT03370133; BE READY: NCT03410992.
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http://dx.doi.org/10.1007/s13555-021-00570-4DOI Listing
July 2021

A clinical perspective on risk factors and signs of subclinical and early psoriatic arthritis among patients with psoriasis.

J Dermatolog Treat 2021 Jun 28:1-9. Epub 2021 Jun 28.

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

Psoriasis is a chronic, immune-mediated disease that includes a broad spectrum of systemic manifestations, complications, and comorbidities. Approximately 20%-30% of patients with psoriasis eventually develop psoriatic arthritis, and up to half of those without psoriatic arthritis experience subclinical musculoskeletal abnormalities. Recognition of early musculoskeletal inflammatory signs in patients with psoriasis is important to understand the extent and severity of this systemic disease, assess the risk of structural joint damage, and ensure timely and effective treatment of the complete spectrum of psoriatic disease. Delayed or ineffective treatment can lead to decreased quality of life, irreversible musculoskeletal damage, and loss of function. In this review, we highlight features of subclinical or early psoriatic arthritis among patients with psoriasis of which dermatologists should be aware. Recent knowledge of features of preclinical psoriatic arthritis in patients with psoriasis is presented. We briefly discuss important risk factors, clinical features, and other characteristics of patients likely to progress from psoriasis to psoriatic arthritis that should be known by dermatologists. Screening tools commonly used in the dermatology clinic to detect psoriatic arthritis are also critically reviewed. Finally, we provide expert commentary for dermatologists concerning the treatment of patients with psoriasis and subclinical signs of early psoriatic arthritis.
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http://dx.doi.org/10.1080/09546634.2021.1942423DOI Listing
June 2021

Musculoskeletal Imaging for Dermatologists: Techniques in the Diagnosis and Management of Psoriatic Arthritis.

Dermatol Ther (Heidelb) 2021 Aug 18;11(4):1199-1216. Epub 2021 Jun 18.

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

Psoriatic arthritis is an inflammatory condition affecting up to 30% of patients with psoriasis. Patients may experience irreversible joint damage if not treated early, and diagnostic delays of even 6 months are associated with radiographic progression and impaired function. Therefore, early detection and intervention are of critical importance in patients with psoriatic arthritis. Given that psoriasis often precedes symptoms of psoriatic arthritis, dermatologists are uniquely positioned to identify patients with psoriatic arthritis early in their disease course, before permanent damage has occurred. Several screening tools have been developed to help dermatologists identify patients who may have psoriatic arthritis, but these tools may not capture patients with subclinical disease or quantify the type and severity of the underlying tissue insult, which is often the presenting sign of psoriatic arthritis. In these cases, a combination of clinical assessment and musculoskeletal imaging (e.g., ultrasound) is required. This review summarizes three common musculoskeletal imaging techniques used in the diagnosis and management of patients with psoriatic arthritis: conventional radiography, ultrasound, and magnetic resonance imaging. Further understanding of musculoskeletal imaging will assist dermatologists in making treatment decisions and allow them to have a more active role in the detection of psoriatic arthritis.
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http://dx.doi.org/10.1007/s13555-021-00565-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322349PMC
August 2021

Signal Detection and Methodological Limitations in a Real-World Registry: Learnings from the Evaluation of Long-Term Safety Analyses in PSOLAR.

Drug Saf 2021 Jun 2;44(6):699-709. Epub 2021 Jun 2.

Yale University, New Haven, CT, USA.

Introduction: Psoriasis Longitudinal Assessment and Registry (PSOLAR) was designed in 2007 as the first disease-based registry for patients with psoriasis.

Objective: The aim of this study was to discuss methodological limitations and post hoc analyses in long-term safety registries using learnings from analyses of a potential safety risk for major adverse cardiovascular events (MACE) in PSOLAR.

Methods: PSOLAR is an international observational study of over 12,000 psoriasis patients that was conducted to meet postmarketing safety commitments for infliximab and ustekinumab. A recent annual review of registry data indicated a potential MACE risk for ustekinumab vs. non-biologics based on prespecified COX model regression analyses, which yielded an adjusted hazard ratio (HR) of 1.533 (95% confidence interval [CI] 1.103-2.131). Therefore, we conducted a comprehensive review of key statistical methodology and implemented post hoc analytical methods to address specific limitations.

Results: The following limiting factors were identified: (1) inclusion of both prevalent and incident (new) users of biologics; (2) unanticipated imbalances in patient characteristics between treatment cohorts at baseline; (3) limited availability of relevant clinical data after enrollment; and (4) divergence of characteristics associated with outcomes among comparator groups over time. The analysis was modified to include only incident users, propensity scores were used to weight HRs, and adalimumab was deemed a more clinically appropriate comparator. The revised HR was 0.820 (95% CI 0.532-1.265), indicating no meaningful increase in MACE risk for ustekinumab.

Conclusion: Our results, which do not support a causal association between ustekinumab exposure and MACE risk, underscore the need for ongoing assessment of analytical methods in long-term observational studies.
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http://dx.doi.org/10.1007/s40264-021-01065-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184557PMC
June 2021

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

J Rheumatol Suppl 2021 Jun;97:10-16

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.

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
June 2021

Prologue: 2020 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

J Rheumatol Suppl 2021 Jun;97:1-3

L.V. McFarland, MS, PhD, Consultant, Public Health Reserves Corps, Seattle, Washington, USA.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) held its annual meeting in 2020 in an online format due to travel restrictions during the coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic. The virtual meeting was attended by 351 rheumatologists, dermatologists, representatives of biopharmaceutical companies, and patient research partners. Similar to previous years, GRAPPA's annual meeting focused on the 3 overlapping missions of education, research, and clinical care of psoriatic disease. Trainee sessions this year included the annual trainee symposium and a grant-writing workshop. Plenary sessions included updates on COVID-19 and psoriatic disease from multispecialty and patient perspectives, and updates on pustular psoriasis and associated musculoskeletal manifestations. Progress on research and updates were presented for the following groups: Collaborative Research Network, Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Working Group, International Dermatology Outcome Measures, Composite Measures, Education Committee, and Treatment Guidelines. New this year were 3 concurrent workshops on ultrasound assessment of joints and entheses, magnetic resonance imaging of psoriatic arthritis, and pustular psoriasis efficacy endpoints; 6 "Meet the Expert" sessions; and facilitated "poster tours." In our prologue, we introduce the papers that summarize this meeting.
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http://dx.doi.org/10.3899/jrheum.201666DOI Listing
June 2021

Efficacy and safety of tildrakizumab in patients with active psoriatic arthritis: results of a randomised, double-blind, placebo-controlled, multiple-dose, 52-week phase IIb study.

Ann Rheum Dis 2021 09 13;80(9):1147-1157. Epub 2021 May 13.

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

Objectives: To evaluate efficacy and safety of the anti-interleukin-23p19 monoclonal antibody tildrakizumab in patients with psoriatic arthritis (PsA).

Methods: In this randomised, double-blind, placebo-controlled, phase IIb study, patients with active PsA were randomised 1:1:1:1:1 to tildrakizumab 200 mg every 4 weeks (Q4W); tildrakizumab 200, 100 or 20 mg Q12W; or placebo Q4W. Patients receiving tildrakizumab 20 mg or placebo switched to tildrakizumab 200 mg Q12W at W24; treatment continued to W52. The primary efficacy endpoint was proportion of patients with ACR20 response (≥20% improvement by American College of Rheumatology criteria) at W24. Secondary efficacy endpoints were assessed without adjustment for multiplicity. Safety was evaluated from treatment-emergent adverse events (TEAEs).

Results: 391/500 patients screened were randomised and treated. At W24, 71.4%-79.5% of tildrakizumab-treated versus 50.6% of placebo-treated patients achieved ACR20 (all p<0.01). Patients receiving tildrakizumab versus placebo generally achieved higher rates of ACR50, Disease Activity Score in 28 joints with C reactive protein <3.2, minimal disease activity and 75%/90%/100% improvement from baseline Psoriasis Area and Severity Index responses at W24 and through W52. Improvement in dactylitis and enthesitis was not observed; results were mixed for other outcomes. Responses in patients switched to tildrakizumab 200 mg at W24 were consistent with treatment from baseline. TEAEs and serious TEAEs occurred in 64.5% and 3.3%, respectively, of all patients through W52 and were comparable among treatment arms.

Conclusions: Tildrakizumab treatment significantly improved joint and skin manifestations of PsA other than dactylitis and enthesitis. Treatment was generally well tolerated through W52. Clinicaltrials.gov NCT02980692.
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http://dx.doi.org/10.1136/annrheumdis-2020-219014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372392PMC
September 2021

Pooled Safety Results Through 1 Year of 2 Phase III Trials of Guselkumab in Patients With Psoriatic Arthritis.

J Rheumatol 2021 May 1. Epub 2021 May 1.

This study was sponsored by Janssen Research & Development. P. Rahman, MD, Memorial University of Newfoundland, St. John's, Newfoundland, Canada; C.T. Ritchlin, MD, MPH, University of Rochester, Rochester, New York, USA; P.S. Helliwell, PhD, University of Leeds, Leeds, UK; W.H. Boehncke, MD, Geneva University Hospitals, Geneva, Switzerland; P.J. Mease, MD, Swedish Medical Center/Providence St Joseph Health and University of Washington School of Medicine, Seattle, Washington, USA; A.B. Gottlieb, MD, PhD, Icahn Medical School at Mount Sinai, New York, New York, USA; S. Kafka, MD, Janssen Scientific Affairs, Horsham, Pennsylvania, USA; A.P. Kollmeier, MD, X.L. Xu, PhD, Janssen Research & Development, San Diego, California, USA; E.C. Hsia, MD, Janssen Research & Development, Spring House, Pennsylvania, USA, and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA; M. Shawi, PhD, Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, Pennsylvania, USA; S. Sheng, PhD, P. Agarwal, PhD, B. Zhou, PhD, P. Ramachandran, MD, MPH, Y. Zhuang, PhD, Janssen Research & Development, Spring House, Pennsylvania, USA; I.B. McInnes, MD, PhD, University of Glasgow, Glasgow, UK. CTR has received research support from AbbVie, Amgen, and UCB, and consultant fees from AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB. PR has received research support from Janssen and Novartis; consultant fees from Abbott, AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB; and speakers bureau support from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. PSH has received consulting fees from Eli Lilly and fees for educational services from Amgen, Janssen, Novartis, and Pfizer. WHB has received research support from Pfizer and consulting fees and speaker bureau support from AbbVie, Almirall, Celgene, Janssen, LEO Pharma, Eli Lilly, Novartis, and UCB. IBM has received research support from AstraZeneca, BMS, Celgene, Janssen, Eli Lilly, Novartis, and UCB, and consultant fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Gilead, Janssen, Novartis, and UCB. ABG has received research support from Boehringer Ingelheim, Incyte, Janssen, Novartis, Sun Pharmaceutical Industries, UCB, and XBiotech; honoraria from Amgen, BMS, Celgene, Janssen, LEO Pharma, Novartis, and UCB Pharma; consultant fees from AnaptysBio, Avotres, Boehringer Ingelheim, Incyte, Lilly ICOS, Novartis, Pfizer, and Sun Pharmaceutical Industries; and stock options from XBiotech. PJM has received research support, consulting fees, and speaker bureau support from AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer, and UCB. SK was an employee of Janssen Scientific Affairs at the time this work was performed; APK, ECH, XLX, SS, PA, BZ, PR, and YZ are employees of Janssen Research & Development; and MS is an employee of Janssen Global Services-these authors own stock or stock options in Johnson & Johnson. Address correspondence to Dr. P. Rahman, 154 LeMarchant Road, St. Clare's Mercy Hospital, St. John's, NL A1C 5B8, Canada. Email: Accepted for publication April 20, 2021.

Objective: Evaluate the safety of guselkumab (monoclonal antibody targeting interleukin [IL]-23p19) in patients with psoriatic arthritis (PsA) through 1 year (1Y) of the phase III DISCOVER-1 and DISCOVER-2 trials.

Methods: Patients with active PsA (n = 1120; biologic-naïve except 118 patients treated with tumor necrosis factor inhibitors in DISCOVER-1) were randomized to subcutaneous guselkumab 100 mg every 4 weeks (Q4W) or at Week 0, Week 4, then every 8 weeks (Q8W); or placebo. At Week 24, patients in the placebo group switched to guselkumab 100 mg Q4W. Treatment continued through 1Y and 2 years for DISCOVER-1 and DISCOVER-2, respectively. In this pooled analysis, patients with ≥ 1 adverse event (AE) through 1Y were standardized for 100 patient-years [100 PYs] of follow-up.

Results: Through Week 24, adverse events (AEs) were consistent between patients treated with placebo and guselkumab (Q4W + Q8W). AEs were 142.8/100 PYs and 150.6/100 PYs, serious AEs were 7.1/100 PYs and 4.4/100 PYs, and AEs leading to study agent discontinuation were 4.1/100 PYs and 3.8/100 PYs, respectively. Through 1Y in patients treated with guselkumab, no uveitis, active tuberculosis, opportunistic infections, or inflammatory bowel disease were observed, and low rates of malignancy and major adverse cardiovascular (CV) events were observed. Injection-site reactions occurred in 1.7%, and antibodies to guselkumab in 4.5% of patients treated with guselkumab through 1Y; the vast majority of antibodies to guselkumab were nonneutralizing. Serum hepatic transaminase elevations (more common with Q4W than Q8W dosing) and decreased neutrophil counts were generally mild, transient, and did not require treatment discontinuation, with minimal change from Week 24 to 1Y.

Conclusion: Guselkumab 100 mg Q4W and Q8W were well tolerated in patients with PsA, with no new safety concerns through 1Y of the phase III DISCOVER trials. Guselkumab safety through 1Y in patients with PsA is consistent with that established in patients with psoriasis who were treated with guselkumab.
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http://dx.doi.org/10.3899/jrheum.201532DOI Listing
May 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

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

Prologue: 2020 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

J Rheumatol 2021 Feb 15. Epub 2021 Feb 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. The source of support to enable these meetings was provided in 2020 by AbbVie, Amgen, Eli Lilly & Co., Janssen, Novartis, Pfizer, UCB, Bristol Myers Squibb, Gilead, Boehringer-Ingelheim, and SunPharma. In addition, our Innovation Partner in 2020 was Nordic Bioscience. K. Callis Duffin, MD, MS, Department of Dermatology, University of Utah, Salt Lake City, Utah, USA; A.B. Gottlieb, MD, PhD, Clinical Professor of Dermatology, Department of Dermatology, Icahn School of Medicine at Mount Sinai, and Co-chair, GRAPPA Publication Committee, New York, New York, USA; D. O'Sullivan, BE, GRAPPA Patient Research Partner, Our Lady's Hospice & Care Services, Rheumatic & Musculoskeletal Disease Unit, Dublin, Ireland; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, Senior Scientist, Krembil Research Institute, Director, Psoriatic Arthritis Program, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada; L.V. McFarland, MS, PhD, Consultant, Public Health Reserves Corps, Seattle, Washington, USA. KCD reports the following conflicts of interest: grants/investigator for Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Bristol Myers Squibb, Stiefel, Novartis, Pfizer, Sienna, UCB, Regeneron, Boehringer-Ingelheim; speaker's bureau for Novartis (nonpromotional only); consultant/advisory board for Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Bristol Myers Squibb, Stiefel, Novartis, Pfizer, Sienna, UCB, Ortho Dermatologic, Boehringer-Ingelheim. There are no conflicts of interest for all other coauthors. Address correspondence to Dr. K. Callis Duffin, University of Utah, 4A330 Dermatology, SOM, 30 North 1900 East, Salt Lake City, UT 84132, USA. Email:

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) held its annual meeting in 2020 in an online format due to travel restrictions during the coronavirus disease 2019 (COVID‑19; caused by SARS-CoV-2) pandemic. The virtual meeting was attended by 351 rheumatologists, dermatologists, representatives of biopharmaceutical companies, and patient research partners. Similar to previous years, GRAPPA's annual meeting focused on the 3 overlapping missions of education, research, and clinical care of psoriatic disease. Trainee sessions this year included the annual trainee symposium and a grant-writing workshop. Plenary sessions included updates on COVID-19 and psoriatic disease from multispecialty and patient perspectives, and updates on pustular psoriasis and associated musculoskeletal manifestations. Progress on research and updates were presented for the following groups: Collaborative Research Network, Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Working Group, International Dermatology Outcome Measures, Composite Measures, Education Committee, and Treatment Guidelines. New this year were 3 concurrent workshops on ultrasound assessment of joints and entheses, magnetic resonance imaging of psoriatic arthritis, and pustular psoriasis efficacy endpoints; 6 "Meet the Expert" sessions; and facilitated "poster tours." In our prologue, we introduce the papers that summarize this meeting.
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http://dx.doi.org/10.3899/jrheum.201666DOI 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

Dupilumab in HIV-positive patients: A case series report of 4 patients.

JAAD Case Rep 2020 Dec 9;6(12):1356-1359. Epub 2020 Oct 9.

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

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http://dx.doi.org/10.1016/j.jdcr.2020.09.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718127PMC
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

Efficacy and Safety of Guselkumab, an Interleukin-23p19-Specific Monoclonal Antibody, Through One Year in Biologic-Naive Patients With Psoriatic Arthritis.

Arthritis Rheumatol 2021 04 17;73(4):604-616. Epub 2021 Mar 17.

Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, Washington.

Objective: Guselkumab, a human monoclonal antibody specific to interleukin-23p19, demonstrated efficacy and safety versus placebo through week 24 of the phase III DISCOVER-2 trial in biologic-naive patients with psoriatic arthritis (PsA). Here we report 1-year DISCOVER-2 findings.

Methods: Adults with active PsA (≥5 swollen and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite standard nonbiologic treatment were randomized to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4 and every 8 weeks thereafter, or placebo with crossover to guselkumab 100 mg every 4 weeks at week 24. We primarily evaluated clinical efficacy through week 52 by imputing missing data (nonresponse for categorical end points; no change/using multiple imputation for continuous end points). Observed radiographic scores and adverse events (AEs) were summarized.

Results: Of 739 randomized, treated patients, 93% completed week 52. The proportions of patients in whom a ≥20% improvement from baseline in American College of Rheumatology criteria (ACR20) was achieved were maintained after week 24, reaching 71% (173 of 245) and 75% (185 of 248) for patients randomized to receive treatment every 4 weeks or every 8 weeks, respectively, by week 52. The proportions of patients in whom ACR50/ACR70 and skin responses, minimal or very low disease activity, and dactylitis or enthesitis resolution were achieved at week 24 were also maintained through week 52. Further, low levels of radiographic progression, along with improvements in physical function and health-related quality of life, were sustained through week 52 with continued guselkumab treatment. Few patients experienced serious infections through week 52, with no evidence of a dosing regimen response or increase from weeks 0-24 (4 of 493 [0.8%]) to weeks 24-52 (3 of 493 [0.6%]) among guselkumab-randomized patients. No patient developed an opportunistic infection or died.

Conclusion: In biologic-naive PsA patients, guselkumab provided sustained improvements across diverse manifestations and maintained a favorable risk-benefit profile through week 52.
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http://dx.doi.org/10.1002/art.41553DOI Listing
April 2021

Clinical efficacy and safety of secukinumab in patients with psoriasis and comorbidities: pooled analysis of 4 phase 3 clinical trials.

J Dermatolog Treat 2020 Oct 21:1-9. Epub 2020 Oct 21.

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

Background: The influence of comorbidities on the efficacy and safety of biologic therapies in psoriasis has not been rigorously explored.

Objective: To assess the incremental burden of comorbidities on clinical efficacy and safety of secukinumab vs. etanercept and placebo among patients with plaque psoriasis pooled from 4 phase 3 trials.

Methods: Efficacy was assessed at week 12 according to achievement of Psoriasis Area and Severity Index (PASI) and Investigator's Global Assessment (IGA; modified 2011) responses. Efficacy comparisons between treatment arms stratified by comorbidity status were made using logistic regression analysis with nonresponder imputation. Relationships between baseline characteristics and clinical responses were evaluated by tests.

Results: Of 2401 patients, 1469 (61.2%) had ≥1 active baseline comorbidity. Regardless of comorbidity status, patients receiving secukinumab were more likely to achieve PASI and IGA responses than those receiving etanercept or placebo at week 12 ( < .05 for all comparisons). Body weight of ≥90 kg was consistently associated with a decreased likelihood of achieving PASI and IGA responses ( < .01 for all comparisons). Safety was comparable across treatment arms stratified by comorbidity.

Conclusions: Secukinumab improved clinical outcomes and was well tolerated in patients with concomitant baseline comorbid conditions.
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http://dx.doi.org/10.1080/09546634.2020.1832187DOI Listing
October 2020

Tildrakizumab efficacy, drug survival, and safety are comparable in patients with psoriasis with and without metabolic syndrome: Long-term results from 2 phase 3 randomized controlled studies (reSURFACE 1 and reSURFACE 2).

J Am Acad Dermatol 2021 Feb 19;84(2):398-407. Epub 2020 Sep 19.

Division of Dermatology, Baylor Scott & White, Dallas, Texas; Texas A&M College of Medicine, Dallas, Texas.

Background: Data for the effect of metabolic syndrome (MetS) on the efficacy and safety of biologic agents for psoriasis treatment are limited.

Objective: To evaluate long-term tildrakizumab efficacy, drug survival, and safety in patients with psoriasis by baseline MetS status.

Methods: Post hoc analyses of up to 3 years of efficacy data and 5 years of safety data from the phase 3, double-blind, randomized controlled reSURFACE 1 and 2 trial (NCT01722331 and NCT01729754) base and extension studies were conducted for patients receiving continuous tildrakizumab 100 or 200 mg.

Results: Of 338 (n = 124/214 in reSURFACE 1/2) and 307 (n = 147/160 in reSURFACE 1/2) patients continuously receiving tildrakizumab 100 and 200 mg, respectively, throughout the studies, 26/44 (21%/21%) and 34/30 (23%/19%) met MetS criteria. Proportions of patients who achieved a 75% improvement in the Psoriasis Area and Severity Index (PASI) in reSURFACE 1/2 were generally comparable among those with versus without MetS at week 52 (tildrakizumab 100 mg, 85%/86% vs 86%/94%; tildrakizumab 200 mg, 76%/87% vs 76%/87%) and through week 148. Results were similar for responders with 90% and 100% improvement in the PASI. Tildrakizumab's safety profile did not vary by MetS status.

Limitations: Small sample size and post hoc analysis limit interpretation.

Conclusion: Long-term tildrakizumab efficacy and safety were comparable between patients with and without MetS.
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http://dx.doi.org/10.1016/j.jaad.2020.09.047DOI Listing
February 2021

The Effect of Tildrakizumab on Cardiometabolic Risk Factors in Psoriasis by Metabolic Syndrome Status: Post Hoc Analysis of Two Phase 3 Trials (ReSURFACE 1 and ReSURFACE 2).

J Drugs Dermatol 2020 Aug;19(8):703-708

Background: Metabolic syndrome (MetS) is the most prevalent comorbidity in psoriasis and increases the risk of cardiovascular disease, diabetes, and mortality. Assessment of impacts of biologic therapies on cardiometabolic risk factors are relatively limited. This study evaluated the effect of tildrakizumab on cardiometabolic risk factors in patients with moderate to severe plaque psoriasis and stratified by MetS status. Methods: In this post hoc analysis of reSURFACE 1/2, tildrakizumab 100 and 200 mg were continuously administered to patients with moderate to severe plaque psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Mean and mean percent changes from baseline were assessed for fasting serum glucose, low/high-density lipoprotein-cholesterol, total cholesterol, triglyceride levels, body weight, and blood pressure at week 64/52 for reSURFACE 1 and 2, respectively, in patients with and without MetS. Results: A total of 369 patients in reSURFACE 1 and 2 received continuous tildrakizumab 100 mg and 330 received tildrakizumab 200 mg; 21.4% and 20.3% in reSURFACE 1 and 2, respectively, had MetS. At week 64/52, mean changes in cardiometabolic risk factors from baseline did not significantly differ regardless of MetS status. Numerically larger mean decreases in fasting glucose, triglycerides, and systolic blood pressure following tildrakizumab 100 mg and in systolic and diastolic blood pressure following tildrakizumab 200 mg were observed in patients with MetS relative to those without MetS. Conclusions: Changes in cardiometabolic disease risk factors following tildrakizumab treatment were limited. Risk factors were not increased in patients with MetS vs without MetS. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5337.
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http://dx.doi.org/10.36849/JDD.2020.5337DOI Listing
August 2020

Development and Content Validation of the Psoriasis Symptoms and Impacts Measure (P-SIM) for Assessment of Plaque Psoriasis.

Dermatol Ther (Heidelb) 2020 Dec 25;10(6):1255-1272. Epub 2020 Aug 25.

Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK.

Introduction: Patients with plaque psoriasis experience a variety of signs and symptoms that can impact daily life, which may not be evaluated by clinician-reported outcomes. This study aimed to develop and assess the content validity of a new patient-reported outcome (PRO) measure to capture patient experiences of the signs, symptoms and impacts of psoriasis and aid integration of the patient perspective in treatment benefit-risk decision-making.

Methods: The psoriasis symptoms and impacts measure (P-SIM) was developed based on a literature search and interviews with five clinical experts in psoriasis to identify frequent signs, symptoms and impacts of psoriasis. Hybrid concept elicitation, cognitive debriefing and usability testing interviews were conducted with moderate to severe psoriasis patients to evaluate the content validity and patient understanding of the preliminary P-SIM. The preliminary P-SIM was refined using initial quantitative analyses of phase 2b data from psoriasis patients to inform the removal of any items.

Results: A preliminary 19-item P-SIM was developed for administration on a hand-held electronic tablet device using a 0-10 numerical response scale over a 24-h recall period. Patient interviews and testing demonstrated most patients interpreted the items and responses as intended, would not re-word any items, felt the responses matched the items and rated the device as easy to use. After quantitative testing, five items were removed from the preliminary 19-item measure because of conceptual overlap, floor effects and/or skewed distributions to generate the final 14-item P-SIM.

Conclusions: The P-SIM questionnaire has good content validity; patients reported it was easy to understand and reflective of their experiences. Following psychometric validation, the P-SIM may be a useful PRO measure for capturing the signs, symptoms and impacts of psoriasis and may support clinician-reported outcomes when assessing treatment benefits in clinical trials.
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http://dx.doi.org/10.1007/s13555-020-00434-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649195PMC
December 2020

Low gene expression of TNF, IL17A, IL23A, and IL12B in tumors: A safety surrogate to predict cancer survival associated with biologic therapies.

J Am Acad Dermatol 2021 Jul 18;85(1):249-252. Epub 2020 Aug 18.

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

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http://dx.doi.org/10.1016/j.jaad.2020.08.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434493PMC
July 2021

Axial psoriatic arthritis: An update for dermatologists.

J Am Acad Dermatol 2021 Jan 31;84(1):92-101. Epub 2020 Jul 31.

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

Psoriasis is a chronic, immune-mediated, systemic, inflammatory disorder characterized by skin plaques and, often, nail disease and arthritis that contribute to reduced quality of life. Psoriatic arthritis-a heterogeneous, inflammatory, musculoskeletal disease that can cause permanent damage to both peripheral and axial joints-is the most common comorbidity of psoriasis. Axial disease occurs in 25% to 70% of patients with PsA, with some patients exclusively experiencing axial joint involvement. Early therapeutic intervention is important for preventing permanent joint and spine damage and loss of functionality in these patients. Because skin symptoms associated with psoriasis often precede psoriatic arthritis, dermatologists are uniquely positioned to play an important role in identifying and treating patients with psoriatic arthritis. Proactive screening of patients with all severities of psoriasis for the signs and symptoms of psoriatic arthritis is key to early diagnosis and intervention. In this review, we discuss the clinical presentation, risk factors, and treatment options for psoriatic arthritis with axial involvement, with the aim of helping dermatologists understand the disease and identify patients who might benefit from further assessment, treatment, and/or referral to a rheumatology practice.
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http://dx.doi.org/10.1016/j.jaad.2020.05.089DOI Listing
January 2021

Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.

J Am Acad Dermatol 2021 Feb 30;84(2):432-470. Epub 2020 Jul 30.

Dermatology Research and Education Foundation, Irvine, California.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.
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http://dx.doi.org/10.1016/j.jaad.2020.07.087DOI Listing
February 2021

Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study.

RMD Open 2020 07;6(2)

Section of Musculoskeletal Disease, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.

Objective: To evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA).

Methods: This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0-3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0-6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses.

Results: Of 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24).

Conclusions: At week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis.

Trial Registration Number: ClinicalTrials.gov: NCT02319759.URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014.
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http://dx.doi.org/10.1136/rmdopen-2020-001217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425189PMC
July 2020

Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial.

Lancet 2020 07;396(10244):110-120

University of Massachusetts Medical School, Worcester, MA, USA.

Background: Vitiligo is a chronic autoimmune disease resulting in skin depigmentation and reduced quality of life. There is no approved treatment for vitiligo repigmentation and current off-label therapies have limited efficacy, emphasising the need for improved treatment options. We investigated the therapeutic potential of ruxolitinib cream in patients with vitiligo and report the efficacy and safety results up to 52 weeks of double-blind treatment.

Methods: We did a multicentre, randomised, double-blind, phase 2 study for adult patients with vitiligo in 26 US hospitals and medical centres in 18 states. Patients with depigmentation of 0·5% or more of their facial body surface area (BSA) and 3% or more of their non-facial BSA were randomly assigned (1:1:1:1:1) by use of an interactive response technology system to receive ruxolitinib cream (1·5% twice daily, 1·5% once daily, 0·5% once daily, or 0·15% once daily) or vehicle (control group) twice daily on lesions constituting 20% or less of their total BSA for 24 weeks. Patients in the control group in addition to patients in the 0·15% once daily group who did not show a 25% or higher improvement from baseline in facial Vitiligo Area Scoring Index (F-VASI) at week 24 were re-randomised to one of three higher ruxolitinib cream doses (0·5% once daily, 1·5% once daily, 1·5% twice daily). Patients in the 0·5% once daily, 1·5% once daily, or 1·5% twice daily groups remained at their original dose up to week 52. Patients, investigators, and the study sponsor (except members of the interim analysis and primary endpoint analysis data monitoring teams) remained masked to treatment assignment throughout the study. The primary endpoint was the proportion of patients achieving a 50% or higher improvement from baseline in F-VASI (F-VASI50) at week 24, assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03099304.

Findings: Between June 7, 2017, and March 21, 2018, 205 patients were screened for eligibility, 48 were excluded and 157 patients (mean age, 48·3 years [SD 12·9]; 73 [46%] male and 84 [54%] female) were randomly assigned to either an intervention group or the control group. 32 (20%) of 157 were assigned to the control group, 31 (20%) to the 0·15% once daily group, 31 (20%) to the 0·5% once daily group, 30 (19%) to the 1·5% once daily group, and 33 (21%) to the 1·5% twice daily group. F-VASI50 at week 24 was reached by significantly more patients given ruxolitinib cream at 1·5% twice daily (15 [45%] of 33) and 1·5% once daily (15 [50%] of 30) than were treated with vehicle (one [3%] of 32). Four patients had serious treatment-emergent adverse events (one patient in the 1·5% twice daily group developed subdural haematoma; one patient in the 1·5% once daily group had a seizure; one patient in the 0·5% once daily group had coronary artery occlusion; and one patient in the 0·5% once daily group had oesophageal achalasia), all of which were unrelated to study treatment. Application site pruritus was the most common treatment-related adverse event among patients given ruxolitinib cream (one [3%] of 33 in the 1·5% twice daily group; three [10%] of 30 in the 1·5% once daily group; three [10%] of 31 in the 0·5% once daily group; and six [19%] of 31 in the 0·15% once daily group)with three [9%] of 32 patients showing application site pruritis in the control group. Acne was noted as a treatment-related adverse event in 13 (10%) of 125 patients who received ruxolitinib cream and one (3%) of 32 patients who received vehicle cream. All treatment-related adverse events were mild or moderate in severity and similar across treatment groups.

Interpretation: Treatment with ruxolitinib cream was associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all doses were well tolerated. These data suggest that ruxolitinib cream might be an effective treatment option for patients with vitiligo.

Funding: Incyte.
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http://dx.doi.org/10.1016/S0140-6736(20)30609-7DOI Listing
July 2020

Interactive, Proof of Concept Clinical Trial Design in Hidradenitis Suppurativa.

Authors:
Alice B Gottlieb

J Invest Dermatol 2021 02 22;141(2):431-433. Epub 2020 Jun 22.

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

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http://dx.doi.org/10.1016/j.jid.2020.06.006DOI Listing
February 2021

Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): Experience with infliximab and other systemic and biologic therapies Errata.

J Drugs Dermatol 2020 Jun;19(6):573-574

Erratum for article "Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): Experience with infliximab and other systemic and biologic therapies." Retrieved from https://jddonline.com/articles/dermatology/S1545961614P1441XJ Drugs Dermatol 2020;19:e35-e36.
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June 2020

Report of the Skin Research Workgroups from the GRAPPA 2019 Annual Meeting.

J Rheumatol Suppl 2020 Jun;96:36-40

From the Department of Dermatology and Medicine, Division of Rheumatology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts; Department of Dermatology, Icahn School of Medicine at Mt. Sinai, New York, New York; Department of Dermatology, Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA.

The International Dermatology Outcome Measures (IDEOM) initiative is a nonprofit organization dedicated to enhancing clinical care and research in dermatology by developing evidence-based, patient-centered outcome measures. At the 2019 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the IDEOM psoriasis working group presented an overview of its selected deliverables and discussed its efforts to agree on meaningful, valid, and feasible outcome measures for quality measurement in psoriasis. The psoriatic arthritis (PsA) workgroup focused on the measurement of PsA symptoms in psoriasis clinical trials, and the measurement of nonspecific musculoskeletal symptoms among patients with psoriasis in psoriasis longitudinal clinical trials and cohort studies.
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http://dx.doi.org/10.3899/jrheum.200125DOI Listing
June 2020
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