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Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Dermatology".

Deadline for manuscript submissions: closed (5 February 2022) | Viewed by 44171

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Special Issue Editor

Dr. Mayumi Komine

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Guest Editor

Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke 329-0498, Japan
Interests: dermatology; keratinocyte biology; psoriasis; psoriatic arthritis; inflammatory reaction; ichthyosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The recent therapeutic development of psoriasis and psoriatic arthritis has been remarkable. Emerging therapies include various biologics, such as anti-TNF, anti-IL12/23, anti-IL-17, and anti-IL-23, and small molecule inhibitors, such as PDE4 inhibitors, Tyk2 inhibitors and JAK inhibitors. In addition to those, we also have conventional therapies, such as retinoids, cyclosporin, and methotrexate, as well as topical therapeutics, such as glucocorticoids and active vitamin D3 derivatives. We now have various options when it comes to treating the patient in front of us, which can however be both a blessing and a curse, as while a wider range of options offers a broader coverage, it also leads to dilemmas about making the right choice of treatment. Accumulating evidence, of course, supports us in our decision making, but we must still rely on our own experiences and those of others. This Special Issue aims to accumulate recent reviews, clinical studies, case series, and case reports on psoriasis and psoriatic arthritis, including both successful and unsuccessful cases, to contribute to the decision making in our daily medical practice.

Dr. Mayumi Komine
Guest Editor

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Keywords

psoriasis
psoriatic arthritis
biologics
small molecule inhibitors
conventional therapies

Published Papers (12 papers)

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Research

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13 pages, 516 KiB

Open AccessArticle

Comparison of Treatment Goals between Users of Biological and Non-Biological Therapies for Treatment of Psoriasis in Japan

by Yukari Okubo, Ann Chuo Tang, Sachie Inoue, Hitoe Torisu-Itakura and Mamitaro Ohtsuki

J. Clin. Med. 2021, 10(24), 5732; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10245732 - 07 Dec 2021

Cited by 3 | Viewed by 2378

Abstract

Background: Previously, our cross-sectional observational study in Japan revealed high (68%) discordance within treatment goals between psoriasis patients and their physicians. Objective: This secondary analysis aimed to determine whether patient and physician users of biologics have higher treatment goals than users of non-biologics. Methods: A survey for both patients and physicians on background characteristics, disease severity, treatment goals, treatment satisfaction, and health-related quality of life was conducted at 54 sites. Association between treatment goals and biologic/non-biologic users was assessed using ordinal logistic regression models. Results: In total, 449 patient-physician pairs agreed to participate; 425 completed the survey and were analyzed. More biologic users than non-biologic users reported complete clearance (Psoriasis Area and Severity Index 100) as a treatment goal (patient-reported: 23.6% vs. 16.1%; physician-reported: 26.9% vs. 2.2%). Biologic users were significantly associated with higher treatment goals than non-biologic users (patient-reported: 1.8 (1.15–2.87) (odds ratio (9 5% CI)), p = 0.01; physician-reported: 11.0 (5.72–21.01), p < 0.01). Among biologic users, higher treatment goals were associated with higher treatment satisfaction (patient- and physician-rated); lower treatment goals were associated with back lesions and increasing patient age (patient-rated) and higher disease severity (physician-rated). Conclusion: Use of biologics among patients with psoriasis was associated with higher treatment goals. Further use of biologics contributed to treatment satisfaction. Appropriate treatment goals that are shared among patients and their physicians may improve treatment outcomes. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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11 pages, 263 KiB

Open AccessArticle

Implementation of the Treat-to-Target Concept in Evaluation of Psoriatic Arthritis Patients

by Tal Gazitt, Muhanad Abu Elhija, Amir Haddad, Idit Lavi, Muna Elias and Devy Zisman

J. Clin. Med. 2021, 10(23), 5659; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10235659 - 30 Nov 2021

Cited by 5 | Viewed by 1645

Abstract

Background: The treat-to-target approach was recently adopted for psoriatic arthritis (PsA) management. Objective: To assess the implementation of the “treat-to-target” (T2T) concept in daily management of PsA by use of composite scores of disease activity versus clinical judgement alone. Methods: A total of 117 PsA patients from a longitudinal PsA cohort were enrolled consecutively in the study during each patient’s first clinic visit during 2016–2017. Clinic notes from the treating rheumatologist were reviewed by an independent rheumatologist, noting clinical impression of disease activity, treatment changes based on clinical judgement, and rationale. Treatment changes were then compared to the use of formal disease activity parameters in Minimal Disease Activity (MDA) and Disease Activity Index for Psoriatic Arthritis (DAPSA) composite measures. All associations were assessed using the chi-square test or the Mann–Whitney test, as appropriate. Results: The 117 PsA patient cohort consisted of 65.5% women, mean age 58.4 ± 13.6 years. Clinical judgement of treating rheumatologist concorded with MDA and DAPSA in 76 (65.5%) and 74 (64.9%) patients, respectively. Agreement between clinical judgement and composite measure criteria did not correlate with patient age, sex, alcohol/tobacco use, or treatment regimens chosen. Disagreement between physician assessment and MDA occurred in 40 (34.5%) cases: in 30 cases, the MDA status was overestimated due to disregard of patient reported outcomes (PRO), while underestimation of MDA status occurred in 25% of cases with treatment changes made in patients with a single active joint or enthesis. Underestimation of disease activity using DAPSA occurred in 22 cases and could be attributed to disregarding tender joint count, patient pain visual analogue scale and C-reactive protein level. Conclusion: In our cohort, agreement between clinical impression and formal composite measure utilization for implementation of T2T strategy occurred in 65% of patients. Discordance resulted from physicians’ overlooking PRO and emphasizing objective findings when using clinical judgement alone. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

11 pages, 1656 KiB

Open AccessArticle

The Antidiabetic Agent Metformin Inhibits IL-23 Production in Murine Bone-Marrow-Derived Dendritic Cells

by Tomoyo Matsuda-Taniguchi, Masaki Takemura, Takeshi Nakahara, Akiko Hashimoto-Hachiya, Ayako Takai-Yumine, Masutaka Furue and Gaku Tsuji

J. Clin. Med. 2021, 10(23), 5610; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10235610 - 29 Nov 2021

Cited by 1 | Viewed by 1761

Abstract

Psoriasis is a chronic inflammatory skin disease, and its immune mechanism has been profoundly elucidated. Biologics targeting interleukin (IL)-23 have prevented the development of psoriasis. As major sources of IL-23, dendritic cells (DCs) play a pivotal role in psoriasis; however, the regulatory mechanism of IL-23 in DCs remains unclear. IL-36γ was reported to reflect the disease activity of psoriasis. Therefore, we hypothesized that IL-36γ may affect IL-23 production in DCs. To reveal the mechanism by which IL-36γ controls IL-23 production in DCs, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-36γ. IL-36γ stimulation upregulated the mRNA and protein expression of Nfkbiz in BMDCs. Nfkbiz knockdown using siRNA transfection partially inhibited the upregulation of IL-23 mRNA expression induced by IL-36γ stimulation. Since NF-κB signaling regulates Nfkbiz expression and the anti-diabetic agent metformin reportedly modulates NF-κB signaling, we examined the effect of metformin treatment on IL-36γ-induced IL-23 production. Metformin treatment impaired the phosphorylation of NF-κB induced by IL-36γ stimulation with the subsequent downregulation of Nfkbiz, resulting in the inhibition of IL-23 production in BMDCs. These data provided evidence that metformin treatment can inhibit IL-36γ-mediated IL-23 production in BMDCs, which might contribute to the prevention of psoriasis. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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Review

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11 pages, 1008 KiB

Open AccessReview

Regulatory Roles of Estrogens in Psoriasis

by Akimasa Adachi and Tetsuya Honda

J. Clin. Med. 2022, 11(16), 4890; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11164890 - 20 Aug 2022

Cited by 4 | Viewed by 2118

Abstract

Psoriasis is a common chronic inflammatory skin disease of the interleukin (IL)-23/IL-17 axis. The severity of psoriasis has been reported as higher in men than in women. The immunoregulatory role of female sex hormones has been proposed to be one of the factors responsible for sex differences. Among female sex hormones, estrogens have been suggested to be significantly involved in the development of psoriasis by various epidemiological and in vitro studies. For example, the severity of psoriasis is inversely correlated with serum estrogen levels. In vitro, estrogens suppress the production of psoriasis-related cytokines such as IL-1β and IL-23 from neutrophils and dendritic cells, respectively. Furthermore, a recent study using a mouse psoriasis model indicated the inhibitory role of estrogens in psoriatic dermatitis by suppressing IL-1β production from neutrophils and macrophages. Understanding the role and molecular mechanisms of female sex hormones in psoriasis may lead to better control of the disease. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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11 pages, 686 KiB

Open AccessReview

Diagnosis and Intervention in Early Psoriatic Arthritis

by Tomoyuki Hioki, Mayumi Komine and Mamitaro Ohtsuki

J. Clin. Med. 2022, 11(7), 2051; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11072051 - 06 Apr 2022

Cited by 8 | Viewed by 4326

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory disorder that affects approximately 20–30% of patients with psoriasis. PsA causes deformities and joint damage, impairing quality of life and causing long-term functional disability. Several recent studies demonstrated that early diagnosis and intervention for PsA prevents permanent invalidity. However, the clinical features of PsA vary and are shared with other differential diseases, such as reactive arthritis, osteoarthritis, and ankylosing spondylitis. The common and overlapping features among these diseases complicate the accurate early diagnosis and intervention of PsA. Therefore, this review focuses on the current knowledge of the diagnosis of early PsA and discusses the meaning of early intervention for early PsA. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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19 pages, 2039 KiB

Open AccessReview

Adherence and Persistence to Biological Drugs for Psoriasis: Systematic Review with Meta-Analysis

by Eugenia Piragine, Davide Petri, Alma Martelli, Agata Janowska, Valentina Dini, Marco Romanelli, Vincenzo Calderone and Ersilia Lucenteforte

J. Clin. Med. 2022, 11(6), 1506; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11061506 - 09 Mar 2022

Cited by 12 | Viewed by 4149

Abstract

Despite the large number of biologics currently available for moderate-to-severe psoriasis, poor adherence and persistence to therapy represent the main issues for both the clinical and economic management of psoriasis. However, the data about adherence and persistence to biologics in psoriasis patients are conflicting. Our aim was to produce summary estimates of adherence and persistence to biologics in adult patients with psoriasis. We performed a systematic review and meta-analysis of observational studies, searching two databases (PubMed and Embase). Sixty-two records met the inclusion criteria, and a meta-analysis was conducted on fifty-five studies. Overall, the proportion of adherent and persistent patients to biological therapy was 0.61 (95% confidence interval: 0.48–0.73) and 0.63 (0.57–0.68), respectively. The highest proportions were found for ustekinumab, while the lowest ones were found for etanercept. The proportions of adherence and persistence to biological drugs in psoriasis patients are sub-optimal. Notably, both proportions largely differ between drugs, suggesting that a more rational use of biologics might ensure better management of psoriasis. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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11 pages, 431 KiB

Open AccessReview

Efficacy and Safety of Different Formulations of Calcipotriol/Betamethasone Dipropionate in Psoriasis: Gel, Foam, and Ointment

by Lidia Rudnicka, Małgorzata Olszewska, Mohamad Goldust, Anna Waśkiel-Burnat, Olga Warszawik-Hendzel, Przemysław Dorożyński, Jadwiga Turło and Adriana Rakowska

J. Clin. Med. 2021, 10(23), 5589; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10235589 - 28 Nov 2021

Cited by 11 | Viewed by 3914

Abstract

Preparations containing calcipotriol combined with betamethasone dipropionate (in the forms of ointment, gel, and foam) are available for the topical treatment of psoriasis. This review summarizes the differences in the efficacy and safety of these formulations, as well as the preferences of patients with various forms of psoriasis (plaque, scalp, and nail psoriasis). It has been documented that foams provide higher bioavailability, resulting in increased efficacy in plaque psoriasis compared to ointments and gels. Gels or foams are preferred by patients for their different practical qualities (e.g., gels for “easy application”, and foams for “immediate relief”). The available data indicate that ointments may be the most effective formulation in nail psoriasis, and gels are preferred by patients with scalp psoriasis because of their cosmetic features. Treatment with a foam formulation is associated with a lower number of medical appointments compared to treatment with an ointment and with a lower probability of developing indications for systemic treatment. The safety profiles of foams, ointments, and gels are comparable, with the most common adverse effect being pruritus at the application site (in 5.8% of the patients). A long-term proactive maintenance therapy markedly reduces the number of relapses and is likely to close the gap between topical and systemic treatment in psoriasis. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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15 pages, 1432 KiB

Open AccessReview

Role of Janus Kinase Inhibitors in Therapy of Psoriasis

by Sylwia Słuczanowska-Głąbowska, Anna Ziegler-Krawczyk, Kamila Szumilas and Andrzej Pawlik

J. Clin. Med. 2021, 10(19), 4307; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10194307 - 22 Sep 2021

Cited by 23 | Viewed by 3148

Abstract

Janus kinases inhibitors are molecules that target Janus kinases—signal transducers and activators of transcription (JAK/STAT). They inhibit this intracellular signal pathway, blocking the gene transcription of crucial proinflammatory cytokines that play a central role in the pathogenesis of many inflammatory and autoimmune diseases, including psoriasis. This process reduces psoriatic inflammation. The JAK inhibitors are divided into two generations. The first generation of JAK inhibitors blocks two or more different Janus kinases. The second generation is more specified and blocks only one type of Janus kinase and has less side effects than the first generation. Tofacitinib, ruxolitinib and baricitinib belong to first generation JAK inhibitors and decernotinib and filgotinib belong to second group. This narrative review summarizes the role of Janus kinase inhibitors in the therapy of psoriasis. Oral JAK inhibitors show promise for efficacy and safety in the treatment of psoriasis. Studies to date do not indicate that JAK inhibitors are superior to recent biologic drugs in terms of efficacy. However, JAK inhibitors, due to their lack of increased incidence of side effects compared to other biologic drugs, can be included in the psoriasis treatment algorithm because they are orally taken. Nevertheless, further studies are needed to evaluate long-term treatment effects with these drugs. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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13 pages, 1112 KiB

Open AccessReview

The Defect in Regulatory T Cells in Psoriasis and Therapeutic Approaches

by Naoko Kanda, Toshihiko Hoashi and Hidehisa Saeki

J. Clin. Med. 2021, 10(17), 3880; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10173880 - 29 Aug 2021

Cited by 32 | Viewed by 5014

Abstract

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin (IL)-23/IL-17 axis. Patients with psoriasis manifest functional defects in CD4⁺CD25⁺ forkhead box protein 3 (Foxp3)⁺ regulatory T cells (Tregs), which suppress the excess immune response and mediate homeostasis. Defects in Tregs contribute to the pathogenesis of psoriasis and may attribute to enhanced inhibition and/or impaired stimulation of Tregs. IL-23 induces the conversion of Tregs into type 17 helper T (Th17) cells. IL-17A reduces transforming growth factor (TGF)-β1 production, Foxp3 expression, and suppresses Treg activity. Short-chain fatty acids (SCFAs), butyrate, propionate, and acetate are microbiota-derived fermentation products that promote Treg development and function by inducing Foxp3 expression or inducing dendritic cells or intestinal epithelial cells to produce retinoic acids or TGF-β1, respectively. The gut microbiome of patients with psoriasis revealed reduced SCFA-producing bacteria, Bacteroidetes, and Faecallibacterium, which may contribute to the defect in Tregs. Therapeutic agents currently used, viz., anti-IL-23p19 or anti-IL-17A antibodies, retinoids, vitamin D3, dimethyl fumarate, narrow-band ultraviolet B, or those under development for psoriasis, viz., signal transducer and activator of transcription 3 inhibitors, butyrate, histone deacetylase inhibitors, and probiotics/prebiotics restore the defected Tregs. Thus, restoration of Tregs is a promising therapeutic target for psoriasis. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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12 pages, 821 KiB

Open AccessReview

Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

by Trung T. Vu, Hanako Koguchi-Yoshioka and Rei Watanabe

J. Clin. Med. 2021, 10(17), 3822; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10173822 - 26 Aug 2021

Cited by 17 | Viewed by 3962

Abstract

Tissue-resident memory T cells (T_RM) stay in the peripheral tissues for long periods of time, do not recirculate, and provide the first line of adaptive immune response in the residing tissues. Although T_RM originate from circulating T cells, T_RM are physiologically distinct from circulating T cells with the expression of tissue-residency markers, such as CD69 and CD103, and the characteristic profile of transcription factors. Besides defense against pathogens, the functional skew of skin T_RM is indicated in chronic skin inflammatory diseases. In psoriasis, IL-17A-producing CD8⁺ T_RM are regarded as one of the pathogenic populations in skin. Although no licensed drugs that directly and specifically inhibit the activity of skin T_RM are available to date, psoriatic skin T_RM are affected in the current treatments of psoriasis. Targeting skin T_RM or using T_RM as a potential index for disease severity can be an attractive strategy in psoriasis. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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19 pages, 1054 KiB

Open AccessReview

Molecular Pathogenesis of Psoriasis and Biomarkers Reflecting Disease Activity

by Masaru Honma and Hiroyoshi Nozaki

J. Clin. Med. 2021, 10(15), 3199; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10153199 - 21 Jul 2021

Cited by 11 | Viewed by 5902

Abstract

Psoriasis is a chronic inflammatory skin disease induced by multifactorial causes and is characterized by bothersome, scaly reddish plaques, especially on frequently chafed body parts, such as extensor sites of the extremities. The latest advances in molecular-targeted therapies using biologics or small-molecule inhibitors help to sufficiently treat even the most severe psoriatic symptoms and the extra cutaneous comorbidities of psoriatic arthritis. The excellent clinical effects of these therapies provide a deeper understanding of the impaired quality of life caused by this disease and the detailed molecular mechanism in which the interleukin (IL)-23/IL-17 axis plays an essential role. To establish standardized therapeutic strategies, biomarkers that define deep remission are indispensable. Several molecules, such as cytokines, chemokines, antimicrobial peptides, and proteinase inhibitors, have been recognized as potent biomarker candidates. In particular, blood protein markers that are repeatedly measurable can be extremely useful in daily clinical practice. Herein, we summarize the molecular mechanism of psoriasis, and we describe the functions and induction mechanisms of these biomarker candidates. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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10 pages, 423 KiB

Open AccessReview

Biologics for Psoriasis during the COVID-19 Pandemic

by Koji Kamiya, Mayumi Komine and Mamitaro Ohtsuki

J. Clin. Med. 2021, 10(7), 1390; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10071390 - 30 Mar 2021

Cited by 10 | Viewed by 4040

Abstract

Psoriasis is a chronic, immune-mediated inflammatory disease that predominantly affects the skin and joints. The recent therapeutic development for psoriasis has been remarkable and biologics have dramatically changed the treatment of psoriasis. In moderate-to-severe cases, systemic therapies are required to control their symptoms and biologics can provide greater efficacy when compared with other types of therapies. The coronavirus disease (COVID-19) pandemic has had a great impact on the lives of many people and has worsened substantially worldwide. During the ongoing COVID-19 pandemic, it still remains unclear whether biologics suppress the immune system and increase the risk of COVID-19. In this review, we have summarized the experience with biologics used for treating psoriasis during the COVID-19 pandemic. Biologics seem to be beneficial to COVID-19 infection. Shared decision-making that is based on updated information is highlighted in the time of COVID-19. Full article

(This article belongs to the Special Issue Psoriasis and Psoriatic Arthritis: How to Treat in the Era of Biologics and Small Molecule Inhibitors?)

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