Oral Phosphodiesterase-4 Inhibitor Research Articles

The Dosing Strategy to Improve Adherence to Roflumilast in Treatment for Chronic Obstructive Lung Disease: A Systemic Review and Meta-Analysis.

The clinical efficacy of roflumilast, an oral phosphodiesterase-4 inhibitor, has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD). However, roflumilast has shown frequent adverse drug reactions (ADRs). This study was performed to investigate the dosing strategy that will improve adherence to roflumilast in COPD. We conducted a systematic review and meta-analysis using PubMed, Embase, and Cochrane Central Register. The dosing strategy for roflumilast was classified into a dose-escalation group and a low-dose group. We investigated clinical outcomes according to dosing strategy. Five clinical trials involving 2424 patients were included. Both the dose-escalation and the low-dose groups showed a decrease in discontinuation rate compared to the standard dosing group for roflumilast (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.67-0.97; P = 0.02 and RR, 0.62; 95% CI, 0.48-0.80; P < 0.01, respectively). In the two strategies, the pooled proportions of discontinuation were 27.9% and 11.7%, respectively. Although the pooled proportion of any ADR was not statistically decreased in the two strategies, diarrhea was significantly reduced in the low-dose group compared to the standard group (RR, 0.58; 95% CI, 0.42-0.82; P < 0.01). The pooled incidence of acute exacerbations was similar between the low-dose and the standard groups (22.9% and 20.1%, respectively; P = 0.27). Our findings show that the two alternative dosing strategies might have the benefit of improving adherence to roflumilast in COPD. Further large-scale trials are required to support our findings.

Apremilast in Erythema Nodosum Leprosum: A Case Series

Erythema nodosum leprosum (ENL) is an immune-mediated inflammatory reaction (antigen-antibody reaction involving complement) of leprosy. Available standard treatment in the form of steroids or thalidomide does not work in all ENL patients. Apremilast is an oral phosphodiesterase-4 inhibitor with potent immunomodulatory action. At present, apremilast is approved for chronic plaque psoriasis and psoriatic arthritis, however, not in ENL. The aim of this study was to assess the effectiveness of apremilast in chronic recalcitrant ENL. It was a case series, in which apremilast was started in 10 consecutive patients with recalcitrant ENL with 10 mg morning dose with a daily increment of 10 mg until day 6, when the recommended dose of 30 mg twice daily for adults is reached. Follow-up was done every 1 month till 6 months. Three patients showed good responses. The drug was well tolerated with few side effects. The most common adverse effect reported was headache (n = 5), followed by nausea (n = 4) and diarrhea (n = 4). Apremilast has lower cost and better safety profile compared to thalidomide and may be an option with limited effectiveness for ENL.

Phosphodiesterase-4 Inhibition in the Management of Psoriasis.

Psoriasis is a common chronic immune-mediated disease with many comorbidities and impacts on quality of life. Among the treatments for psoriasis, phosphodiesterase-4 (PDE4) inhibitors are emerging with expanding options. PDE4 inhibitors play a pivotal role in the inflammatory cascade by degrading cyclic adenosine monophosphate (cAMP), contributing to pro-inflammatory mediator production. Apremilast, an oral PDE4 inhibitor, is approved for psoriasis. While effective, its adverse effects can limit its utility. Roflumilast, a topical PDE4 inhibitor, was also recently approved for psoriasis and shows promise in clinical trials. Crisaborole, a PDE4 inhibitor approved for atopic dermatitis, has also been studied in psoriasis. This review summarizes evidence from randomized clinical trials regarding the efficacy and safety of PDE4 inhibitors in psoriasis treatment. By highlighting their potential benefits and limitations, this review provides valuable insights for clinicians and researchers aiming to optimize psoriasis management.

Oral small-molecule tyrosine kinase 2 and phosphodiesterase 4 inhibitors in plaque psoriasis: a network meta-analysis.

Orally administered small-molecule drugs including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors are new candidates for systemic therapy in plaque psoriasis. However, no previous articles evaluated the benefit and risk profile of TYK2 and PDE4 inhibitors in psoriasis. The objective of this study was to compare the efficacy and safety of oral small-molecule drugs, including TYK2 and PDE4 inhibitors, in treating moderate-to-severe plaque psoriasis. PubMed, Embase, and Cochrane library were searched for eligible randomized clinical trials (RCTs). Response rates for a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment score of 0 or 1 (PGA 0/1) were used for efficacy assessment. Safety was evaluated with the incidence of adverse events (AEs). A Bayesian multiple treatment network meta-analysis (NMA) was performed. In total, 13 RCTs (five for TYK2 inhibitors and eight for PDE4 inhibitors) involving 5274 patients were included. The study found that deucravacitinib at any dose (except for 3 mg QOD), ropsacitinib (200 and 400 mg QD), and apremilast (20 and 30 mg BID) had higher PASI and PGA response rates than placebo. In addition, deucravacitinib (3 mg BID, 6 mg QD, 6 mg BID, and 12 mg QD), and ropsacitinib (400 mg QD) showed superior efficacy than apremilast (30 mg BID). In terms of safety, deucravacitinib or ropsacitinib at any dose did not lead to a higher incidence of AEs than apremilast (30 mg BID). The ranking analysis of efficacy revealed that deucravacitinib 12 mg QD and deucravacitinib 3 mg BID had the highest chance of being the most effective oral treatment, followed by deucravacitinib 6 mg BID and ropsacitinib 400 mg QD. Oral TYK2 inhibitors demonstrated satisfactory performance in treating psoriasis, surpassing apremilast at certain doses. More large-scale, long-term studies focusing on novel TYK2 inhibitors are needed. PROSPERO (ID: CRD42022384859), available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859, identifier CRD42022384859.

Effect of Oral Drug Apremilast on Histopathological Changes in Patients of Plaque Psoriasis: A Prospective Observational Study

Introduction: Psoriasis is a chronic non infectious recurrent papulosquamous inflammatory disorder characterised by vascular alterations such as angiogenesis, dilatation, increased endothelial venule generation, epidermal keratinocyte hyperproliferation, and aberrant differentiation, and lymphocytic invasion of T-cells. The aetiopathogenesis of disease is influenced by both hereditary and environmental factors. Pathogenesis is significantly influenced by immune dysregulation, which affects both innate and acquired immunity. A relatively recent medication for the management of moderate to severe plaque psoriasis is apremilast, an oral phosphodiesterase-4 inhibitor. Compared to other immune-suppressing drugs used in psoriasis apremilast causes no reactivation of tuberculosis or opportunistic infections, does not need dose adjustment in elderly or patients with hepatic impairment, and is not contraindicated in diabetes, ischaemic heart disease, or congestive cardiac failure. Due to its advantage of the absence of the need for laboratory monitoring, the patients on long-term methotrexate can also be switched to apremilast. Aim: To evaluate the histopathological changes in the skin of all plaque psoriatic patients treated with oral drug apremilast. Materials and Methods: This hospital-based prospective study was done in the Department of Pathology at the Rajasthan University of Health Sciences (RUHS), Jaipur, India for a period of one year from February 2020 to January 2021 comparing the efficacy of Apremilast clinically by evaluating plaque psoriasis patients’ by Psoriasis Area and Severity Index (PASI) scores. Patients of all age groups with a clinical diagnosis of psoriasis were subjected to a punch biopsy from an active lesion by a dermatologist. For histopathological examination, biopsy was taken from the lesion before starting treatment with apremilast and after four weeks of apremilast therapy. The subsequent changes in the form of histopathological score and PASI score were analysed and compared with the previous score to study the effect of oral drug apremilast. Results: Total of 100 patients enrolled in the study with the mean age 39.14 years including 59% males and 41% females. Main site of lesion was back, hand and leg. The PASI score at the first visit was 11.28 and at the second visit were 7.27 with the improvement 35.54% which was statistically significant from first visit (p-value&lt;0.001). The histopathological score at the first visit was 15.98 and at the second visit were 10.06 with the improvement 37.1%. Conclusion: Apremilast was found to be a safe and effective treatment for psoriasis patients, and this impact was unaffected by confounding variables.

Efficacy and safety profile of phosphodiesterase 4 inhibitor in the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.

BackgroundSystemic therapy is an important treatment for psoriasis. Phosphodiesterase 4 (PDE4) inhibitors are new candidates for psoriasis therapy.ObjectivesTo evaluate the efficacy and safety of PDE4 inhibitors in psoriasis.MethodRandomized clinical trials with PDE4 inhibitors vs placebos in patients with psoriasis were identified from MEDLINE, Embase, Cochrane Controlled Register of Trials, ClinicalTrials.gov, from inception to July 14, 2022. The study was registered in PROSPERO (CRD42022345700).Results18 studies were identified, 9 of which included moderate-to-severe plaque psoriasis, 2 mild-to-moderate plaque psoriasis, and 7 psoriatic arthritis. A total of 6036 patients were included. Only one oral PDE4 inhibitor, apremilast, met the inclusion criteria. Overall, compared with the placebo, apremilast was associated with higher response rates in PASI-75 (RR, 3.22; 95% CI, 2.59-4.01), ScPGA of 0 or 1 (RR, 2.21; 95% CI, 1.69-2.91), PPPGA of 0 or 1 (RR 2.33; 95%CI, 1.16-4.66), and a significant decrease in NPASI (SMD, -0.46; 95% CI, -0.58 to -0.33). There were no significant differences in serious adverse events. Subgroup analyses showed that significantly more patients achieved PASI-75 after 16 weeks of therapy with apremilast of 20 mg bid (RR, 2.82; 95% CI, 2.01-3.95) and 30 mg bid (RR, 4.08; 95% CI, 3.12-5.33). Heterogeneity was not significant across studies.ConclusionApremilast is a safe and effective treatment for plaque psoriasis and psoriatic arthritis, especially for difficult-to-treat sites.Systematic review registration https://www.crd.york.ac.uk/prospero, identifier (CRD42022345700).

Non-FDA-Approved Uses of Apremilast in Dermatology: A Review of Current Available literature

Introduction: Apremilast, an oral phosphodiesterase-4 inhibitor, decreases the production of pro-inflammatory cytokines including tumour necrosis factor-α, interleukin-12/23, IL-12, IL-2, and interferon-γ; while upregulating the anti-inflammatory cytokine IL-10. Its pan-immunomodulatory nature has led to its use in managing various immune-mediated dermatoses for non-FDA-approved indications. Objectives: To review and analyze the use of Apremilast in Non-FDA-approved indications in current available literature. Materials and methods: PubMed, EMBASE, SCOPUS, and Google scholar databases were searched with the parameters “Apremilast”, “Apremilast NOT Psoriasis*”, “Apremilast NOT Behçet’s*”, and “Apremilast NOT arthritis*”. A total of 45 relevant articles were chosen for review. Results: We found 22 indications in dermatology where apremilast has been used without FDA approval. The best evidence was for treatment in Atopic Dermatitis, Alopecia Areata, and Hidradenitis Suppurativa, with randomized controlled trials. Prospective open-label trials were found for Cutaneous Sarcoidosis, Lichen Planus, Rosacea, and Vitiligo. Individual case series and reports were found for Acrodermatitis Continua of Hallopeau, Dermatomyositis, Disseminated Granuloma Annulare, Erythema Nodosum Leprosum, Morphea, Pityriasis Rubra Pilaris, Hailey-Hailey Disease, Recurrent Erythema Multiforme, and Folliculitis Decalvans, Prurigo Nodularis, Perforating Dermatoses, Chronic Actinic Dermatitis, and Hand Eczema, and Epidermolysis Bullosa Simplex-Generalised Severe Type. Apremilast has shown varied efficacy despite a better safety profile and tolerability over a long duration compared to conventional immunosuppressant drugs and placebo. Conclusion: Apremilast has been used for varied non-FDA-approved indications in dermatology with variable efficacy. Better controlled, randomized studies with adequate sample size and drug comparisons are needed for better analyses.

33356 A multinational chart review to examine gastrointestinal symptoms and their management in patients treated with apremilast for plaque psoriasis

Background: Diarrhea and nausea are the most common adverse events observed in phase 3 clinical trials and real-world studies of apremilast, an oral phosphodiesterase-4 inhibitor indicated for moderate-to-severe plaque psoriasis.

Can Phosphodiesterase 4 Inhibitor Therapy Be Used in Respiratory Diseases Other Than Chronic Obstructive Pulmonary Disease?

Selective phosphodiesterase 4 (PDE4) inhibitors have been extensively studied for the treatment of various respiratory diseases due to their broad anti-inflammatory and/or bronchodilator effects. Roflumilast, an oral selective PDE4 inhibitor, is currently used as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) with chronic bronchitis. Despite its proven efficacy in other respiratory disorders, including asthma, no other PDE4 inhibitor is approved for respiratory pathologies. This systematic review summarizes the therapeutic action of PDE4 inhibitors, their limitations, recent therapeutic success, and future targets for their use in respiratory diseases other than COPD. An electronic literature search was conducted on four databases, namely, PubMed, PubMed Central, Google Scholar, and ScienceDirect, to collect data on related studies done in humans and published in the English language in the last five years. After extensive analysis and quality appraisal, 11 studies were eligible and thus included in this review, consisting of two randomized controlled trials (RCT), one systematic review and meta-analysis, and eight literature reviews. Roflumilast is not approved for the treatment of asthma due to associated adverse effects and comparable efficacy to inhaled corticosteroids, which are considered the mainstay of asthma maintenance therapy. Hence, the importance of balancing the efficacy with minimizing the side effects is highlighted. Tanimilast (CHF6001), an inhalational selective PDE4 inhibitor, and ensifentrine, a combined PDE3/4 inhibitor, demonstrate the recent therapeutic success in asthma and warrant further large-scale clinical studies. Future researchers will focus on the specific endotype than the phenotype in asthma as a meaningful therapeutic approach due to the high heterogeneity noted in asthma. Current evidence suggests the possibility of PDE4 inhibitors as a novel therapeutic option for chronic cough, allergic rhinitis, and cystic fibrosis. Further evidence from new studies is eagerly anticipated to better understand the efficacy and safety of PDE4 inhibitors in these respiratory diseases.

573 ME3183, a novel phosphodiesterase-4 (PDE4) inhibitor, showed potent suppressive effects on pathogenic cytokine expression in cultures of peripheral blood mononuclear cells (PBMC) from psoriasis patients and on psoriatic features in mouse models

Introduction & Objectives: PDE4 plays an important role in the immune system. ME3183, an oral PDE4 inhibitor, has shown anti-inflammatory effects in non-clinical studies. Here, we evaluated the therapeutic potency of ME3183 for psoriasis both in vitro and in vivo and compared it with apremilast, a marketed oral PDE4 inhibitor. Methods: In the in vitro assay, cultures of PBMC from 10 psoriasis (Ps) patients were stimulated with lipopolysaccharide (LPS) in the presence of ME3183 or apremilast, and the level of tumor necrosis factor-alpha (TNF-α) was measured. In the psoriasis model, imiquimod was applied on shaved dorsal skin for 6 consecutive days. In the arthritis model, collagen antibody was injected on Day 0 and LPS on Day 3. In both models, ME3183 or apremilast was administered twice daily, and clinical score and histological findings were evaluated. Gene expression by real-time polymerase chain reaction and cell population were analyzed in the psoriasis model and paw thickness in the arthritis model. Results: In cultures of PBMC from Ps patients, ME3183 showed a 114-fold inhibitory activity against TNF-α production than apremilast. We next evaluated the effects of ME3183 on psoriasis and arthritis in vivo. In the psoriasis model, ME3183 significantly ameliorated the psoriatic score, epidermal thickness, gene expressions of interleukin (IL)-17A and IL-23p19 and skin infiltration of IL-17A+ cells. In the arthritis model, ME3183 significantly suppressed the arthritis score and paw thickness. In both models, ME3183 was effective at low doses compared to apremilast. Conclusions: Our results indicated that ME3183 had potent anti-psoriatic effects via suppression of pathogenic cytokine expression. ME3183 may have higher therapeutic effects on Ps and psoriatic arthritis compared to the current oral PDE4 inhibitor. The clinical efficacy of ME3183 will be evaluated in the P2a study with Ps patients.

Apremilast Prolongs the Time to First Biologic Therapy in Japanese Patients with Psoriasis

IntroductionBiologic agents are used in patients with severe psoriasis who have not adequately responded to existing conventional systemic therapies. However, only a limited number of medical institutions in Japan are approved to use them, and their relatively high cost represents a substantial burden to patients. Apremilast is an oral phosphodiesterase-4 inhibitor approved in Japan for the treatment of psoriasis vulgaris in adult patients with an inadequate response to topical therapies and psoriatic arthritis in adult patients with active disease. To date, a large-scale real-world study of treatment patterns and costs associated with apremilast in Japan has not been conducted. The objective of this study was to assess whether apremilast can prolong time to first biologic therapy use and decrease total medical cost.MethodsUsing the Medical Data Vision hospital-based claims database, 506 psoriasis patients were propensity score matched and analyzed (apremilast: n = 253; non-apremilast: n = 253).ResultsThe incidence rate of first biologic therapy use per 1000 patient-years was significantly lower in the apremilast group than in the non-apremilast group (30.3 vs. 107.6; P < 0.001), and the total medical costs per month were significantly lower in the apremilast group than in the non-apremilast group (76,594 yen/month vs. 102,411 yen/month, P < 0.001). In a sensitivity analysis of a propensity-score-matched subset of eligible patients prescribed biologics during the follow-up period (apremilast: n = 14; non-apremilast: n = 14), the incidence of first biologic therapy use was 2,797.6 per 1000 patient-years (95% CI: 1,656.9, 4,723.6) in the non-apremilast group and 856.1 per 1000 patient-years (95% CI: 507.0, 1,445.5) in the apremilast group.ConclusionThese results suggest that apremilast prolongs the time to first biologic therapy use in patients with psoriasis, thereby reducing the total medical cost and decreasing the economic burden on patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00659-w.

Tanimilast, A Novel Inhaled Pde4 Inhibitor for the Treatment of Asthma and Chronic Obstructive Pulmonary Disease.

Chronic respiratory diseases are the third leading cause of death, behind cardiovascular diseases and cancer, affecting approximately 550 million of people all over the world. Most of the chronic respiratory diseases are attributable to asthma and chronic obstructive pulmonary disease (COPD) with this latter being the major cause of deaths. Despite differences in etiology and symptoms, a common feature of asthma and COPD is an underlying degree of airways inflammation. The nature and severity of this inflammation might differ between and within different respiratory conditions and pharmacological anti-inflammatory treatments are unlikely to be effective in all patients. A precision medicine approach is needed to selectively target patients to increase the chance of therapeutic success. Inhibitors of the phosphodiesterase 4 (PDE4) enzyme like the oral PDE4 inhibitor roflumilast have shown a potential to reduce inflammatory-mediated processes and the frequency of exacerbations in certain groups of COPD patients with a chronic bronchitis phenotype. However, roflumilast use is dampened by class related side effects as nausea, diarrhea, weight loss and abdominal pain, resulting in both substantial treatment discontinuation in clinical practice and withdrawal from clinical trials. This has prompted the search for PDE4 inhibitors to be given by inhalation to reduce the systemic exposure (and thus optimize the systemic safety) and maximize the therapeutic effect in the lung. Tanimilast (international non-proprietary name of CHF6001) is a novel highly potent and selective inhaled PDE4 inhibitor with proven anti-inflammatory properties in various inflammatory cells, including leukocytes derived from asthma and COPD patients, as well as in experimental rodent models of pulmonary inflammation. Inhaled tanimilast has reached phase III clinical development by showing promising pharmacodynamic results associated with a good tolerability and safety profile, with no evidence of PDE4 inhibitors class-related side effects. In this review we will discuss the main outcomes of preclinical and clinical studies conducted during tanimilast development, with particular emphasis on the characterization of the pharmacodynamic profile that led to the identification of target populations with increased therapeutic potential in inflammatory respiratory diseases.

The Use of Apremilast in Psoriasis: An Indian Perspective on Real-World Scenarios.

Apremilast, an oral phosphodiesterase-4 inhibitor, is approved for use in the management of psoriasis and psoriatic arthritis. Although its efficacy and safety have been well established in clinical studies, in real-world settings, different practice scenarios have been reported. This review paper serves to evaluate clinical real-world scenarios and aspects of treatment for which the information in the literature was considered to be lacking or controversial. Following a literature review, a panel of five dermatologists with expertise in psoriasis considered five scenarios; namely, the positioning of apremilast in psoriasis, its use in difficult-to-treat areas, special conditions and populations, safety, dose titration and dose in maintenance therapy. These were then assessed with psoriasis experts in India using a web-based questionnaire. A total of 28 questions were discussed regarding these scenarios. According to the responses, apremilast is effective in stable mild to moderate psoriasis as monotherapy and in severe psoriasis in combination. Also, a positive response was received with regard to its effectiveness in difficult locations such as the scalp, palms and soles. To reduce adverse effects, prolonged titration therapy over 4 weeks is required and lower doses can be prescribed to maintain remission. Apremilast therapy should be continued for a minimum of 8 weeks once initiated to achieve the desired results, and the total duration of therapy should be about 24 weeks for better efficacy. It is also effective in many other cases, such as obese patients, patients with hepatitis B or C and HIV, or patients on polypharmacy. It was also reported that apremilast requires less prescreening and monitoring than other conventional and biologic systemic therapies. Overall, apremilast is an attractive option for the individualized treatment of psoriasis owing to its favorable safety profile, its ease of oral administration without the need for screening or ongoing laboratory monitoring, and its positive impact on symptoms and lesions in difficult-to-treat areas.

Effectiveness and safety of apremilast in biologic-naïve patients with moderate psoriasis treated in routine clinical practice in Greece: the APRAISAL study.

Apremilast is an oral phosphodiesterase-4 inhibitor indicated for patients with moderate-to-severe chronic plaque psoriasis and active psoriatic arthritis. To examine the effectiveness of apremilast on Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI) and nail, scalp and palmoplantar involvement, when administered prior to biologics. This 52-week real-world study included biologic-naive adults with moderate psoriasis (psoriasis-involved body surface area 10% to <20%, or PASI 10 to <20 and DLQI 10 to <20). Apremilast was initiated ≤7days before enrolment. Data from the first 100 eligible patients who completed 24weeks (W24) of observation (or were prematurely withdrawn) are presented in this interim analysis using the last-observation-carried-forward imputation method. Eligible patients (mean age: 49.9years; 71.0% males; median disease duration: 8.0years) were consecutively enrolled between April and October 2017, by 18 dermatology specialists practising in hospital outpatient settings in Greece. Baseline DLQI (median: 12.0) and PASI (median: 11.7) scores improved (P<0.001) at all postbaseline timepoints (Weeks 6, 16 and 24; W24 median decreases: 9.0 and 9.4 points respectively). At W24, DLQI ≤5, DLQI 0 or 1, and PASI-75 response rates were 63.0%, 25.0% and 48.0% respectively. The Nail Psoriasis Severity Index score in patients with baseline nail involvement (n=57) decreased at all postbaseline timepoints (P<0.001; W24 median decrease: 20.0 points). At W24, 50.0% and 51.7% of patients with baseline scalp (n=76) and palmoplantar (n=29) involvement respectively achieved postbaseline Physician's Global Assessment (PGA) score of 0 or 1 if baseline score was ≥3, or 0 if baseline score was 1 or 2. The adverse drug reaction rate was 21.0% (serious: 2.0%). These interim results indicate that through 24weeks, apremilast improved quality of life and reduced disease severity in biologic-naive patients with moderate plaque psoriasis, while demonstrating safety consistent with the known safety profile.

Review of Apremilast Combination Therapies in the Treatment of Moderate to Severe Psoriasis.

Psoriasis is a chronic inflammatory skin condition resulting from the dysregulation of cytokines. Apremilast, an oral phosphodiesterase-4 inhibitor is approved by the Federal Drug Administration (FDA) for the treatment of moderate to severe plaque psoriasis in patients who are eligible for phototherapy or systemic therapy. The drug increases cyclic adenosine monophosphate, cAMP, modulating the expression of pro-inflammatory cytokines. This review aims to explore and categorize current literature describing the efficacy and safety profile of the addition of apremilast to existing therapies including topicals, phototherapy, and systemic agents for the treatment of psoriasis. One database was used for the literature search. Seventeen studies with 617 patients met inclusion criteria and were included. Fifteen studies demonstrated beneficial results with excellent safety and efficacy of apremilast combination therapy (CT). Apremilast has been shown to improve the quality of life and reduce symptom severity in moderate to severe psoriasis. The drug&rsquo;s simple dosing schedule with mild side effect profile makes it a practical option for patients as combination therapy. J Drugs Dermatol. 2021;20(8):837-843. doi:10.36849/JDD.5845.

Phosphodiesterase-4 Inhibition in Psoriasis.

Psoriasis is a chronic immune-mediated inflammatory disorder. Phosphodiesterase-4 (PDE-4) is an enzyme that mediates inflammatory responses and plays a role in psoriasis pathogenesis. PDE-4 degrades its substrate cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP), which subsequently leads to the production of pro-inflammatory mediators. Inhibitors of PDE-4 work by blocking the degradation of cAMP, which leads to a reduction in inflammation. Apremilast is the only approved oral PDE-4 inhibitor for the treatment of psoriasis. While it is effective for some patients, it may be limited by adverse effects in others. A topical PDE-4 inhibitor, roflumilast, is being investigated in psoriasis and showing promising results. Crisaborole, a topical PDE-4 inhibitor approved for use in atopic dermatitis, has also been investigated in psoriasis. This is an updated comprehensive review to summarize the currently available evidence for the PDE-4 inhibitors apremilast, roflumilast and crisaborole in the treatment of psoriasis, with a focus on data from randomized clinical trials.

Roflumilast: A Review of Chronic Obstructive Pulmonary Disease (COPD) Treatment

Abstract Chronic Obstructive Pulmonary Disease (COPD) is a chronic airway inflammation with resulting progressive airflow limitation that has a high incidence, morbidity, and mortality. Roflumilast is an oral phosphodiesterase-4 inhibitor as a therapy to decrease the risk of COPD exacerbations in patients with moderate-severe COPD with a history of chronic bronchitis. Roflumilast can be given orally once daily as a single or combination drug. It can be used as COPD moderate-severe but also more beneficial as COPD mild treatment. The efficacy of Roflumilast can prevent exacerbations of repetition and can fixed lung function both in terms of FEV1 and vital capacity to force. The incidence of side effects, which are diarrhea and digestive disorders. The cost-effectiveness showed that Quality of life patient with Roflumilast is better than the group without additional. This paper aimed to review systematically Roflumilast as COPD treatment for the clinical application.Keywords : COPD, Roflumilast, phosphodiesterase-4 inhibitorCorrespondence : fauna@staff.ubaya.ac.id

Combination of apremilast and narrowband ultraviolet B light in the treatment of generalized vitiligo in skin phototypes IV to VI: A randomized split-body pilot study

To the Editor: Apremilast is an oral phosphodiesterase-4 inhibitor that is approved for the treatment of psoriasis.1 It was shown to be effective in controlling progression of vitiligo,2 but another study found that apremilast does not bring any additional benefit to narrowband ultraviolet B light (NB-UVB) phototherapy.3 That study, however, included a low proportion of skin phototypes (SPTs) IV to VI and lacked the advantage of a bilateral comparison study design. Our study evaluated the efficacy of apremilast plus NB-UVB phototherapy compared with NB-UVB phototherapy alone in patients with SPTs IV to VI with generalized vitiligo (≥20% body surface area).

Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.

Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.

Possibility of combined therapy with an oral phosphodiesterase-4 inhibitor (apremilast) and dihydrofolatereductase inhibitor (methotrexate) in patients with psoriatic arthritis plaque psoriasis

Background: Data on the possible combinations of apremilast with other types of psoriasis therapy is limited.&#x0D; Description of clinical cases: We present the data on the efficacy and safety of combination therapy of the selective phosphodiesterase 4 inhibitor and dihydrofolatereductase inhibitor (methotrexate) for the treatment of psoriasis and psoriatic arthritis in patients with moderate-to-severe plaque psoriasis and active psoriatic arthritis with lack of efficacy of methotrexate in the anamnesis. The selective phosphodiesterase 4 inhibitor (apremilast) was administered according to the prescription. The severity psoriatic arthritis of was estimated by PASI. The effectiveness of therapy was evaluated at week 14. Due to the lack of effect, methotrexate was added subcutaneously at week 14. The effectiveness of combination therapy was assessed at week 26. In both cases, the significant clinical improvement was reached (patients reached PASI 75 and PASI 90), a decrease of the psoriatic arthritis activity according to the DAS28 and DAPSA.&#x0D; Conclusion: These clinical cases demonstrate the efficacy and safety of combined therapy with methotrexate and apremilast inpatients with active psoriatic arthritis and moderate to severe plaque psoriasis.