Use Of Apremilast Research Articles

Effectiveness of Apremilast in Real Life in Patients with Psoriasis: A Longitudinal Study.

Apremilast is an oral selective phosphodiesterase-4 inhibitor developed recently for psoriasis treatment. The aim of this study is to assess the real-life outcomes of use of apremilast in patients with psoriasis in everyday clinical practice. A total of 159 adult patients (90 males) with plaque psoriasis were included in the study. Fifty of the patients (31%) had psoriatic arthritis. All patients started apremilast at the time of enrolment. There was a marked improvement in Psoriasis Area and Severity Index, body surface area and Dermatology Life Quality Index scores across the follow-up period (12 months). The improvements in these scores were also consistent when the patients were stratified according to increasing body mass index. Only 10.6% of the patients discontinued apremilast, because of no response. In conclusion, apremilast is an effective and safe treatment in patients with psoriasis, and its effect is not influenced by body mass index.

Successful Treatment of Refractory Palmoplantar Pustular Psoriasis With Apremilast: A Case Series.

Introduction: Palmoplantar pustular psoriasis (PPPP) is a debilitating inflammatory skin disorder of the palms and soles that poses a high burden on affected patients. Satisfactory treatment response is rarely achieved using current treatment options, little is known about the potential benefit of the PDE4 inhibitor apremilast in the treatment of refractory PPPP patients. We aimed to evaluate the use of apremilast in PPPP patients.Patients and Methods: Six patients, four with severe physician global assessment (PGA) = 3 on a scale of 0–4 and two with very severe (PGA = 4) treatment-refractory PPPP [mean age (years ± SD): 56.2 ± 15.6], were included in this study. Five patients had concomitant psoriatic arthritis (PsA). Prior to apremilast administration, topical corticosteroids, psoralen-UVA and multiple systemic oral and biologic anti-inflammatory treatments were insufficient to improve their skin condition or had to be discontinued due to adverse events. Apremilast (titrated to a maintenance dose of 30 mg 2x/d) was commenced in all patients with clinical follow-up over 18 months.Results: Within the first 4 weeks of treatment, each patient's symptoms improved as assessed by PGA score. At 3 months, four patients had a mild PGA score and two were cleared from PPPP. After 18 months of follow-up, three patients improved from PGA = 3 to PGA = 1 and one patient from PGA = 4 to PGA = 1. Two patients discontinued treatment, one due to a lack of efficacy against PsA and the other to a desire to have a child. However, both patients recorded improvements before discontinuing treatment.Conclusion: Apremilast may be a promising treatment option for refractory and severely affected PPPP patients. Our observation, however, requires further validation.

The Use of Apremilast in Psoriasis: A Delphi Study

BackgroundExperience in the use of apremilast in clinical practice complements the information available from pivotal clinical trials. Materials and methodsFollowing a review of the literature, a panel of dermatologists with expertise in the management of psoriasis considered 5 scenarios in which the evidence supporting the use of apremilast to treat moderate psoriasis is insufficient or controversial. These scenarios were then assessed using a Delphi questionnaire. ResultsConsensus was reached on 96 (67%) of the 143 items (positive in 85 and negative in 11). The therapeutic goal for apremilast should be based on 4 outcomes: clinical response, symptoms, quality of life, and patient satisfaction. The scenario in which the use of apremilast was considered to have the greatest possibility of success was in patients with stable moderate psoriasis. Most of the clinicians considered apremilast to be an appropriate treatment when conventional therapies fail or are contraindicated, preferably before the prescription of biologic therapy. Consensus was reached that apremilast is an appropriate treatment for psoriasis in difficult locations, such as the scalp or the palms and soles. It was also agreed that apremilast requires less prescreening and monitoring than other conventional and biologic systemic therapies. ConclusionsApremilast could be a treatment option for patients with a different profile to that of clinical trial participants. The limitations of this proposal are the absence of consensus on the definition of moderate psoriasis, the lack of real-world evidence on the use of apremilast, and certain aspects related to tolerability.

A cost-effectiveness and budget impact analysis of apremilast in patients with psoriasis in the Italian setting

Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with moderate-to-severe plaque psoriasis (defined as a psoriasis area severity index [PASI] ≥ 10), who failed to respond to, had a contraindication to, or were intolerant to other systemic therapies, within the Italian National Health Service (NHS).Materials and methods: A Markov state-transition cohort model adapted to the Italian context was used to compare the costs of the currently available treatments and of the patients’ quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for psoriasis in Italy, who would be eligible for treatment with apremilast.Results: Over 5 years, the cost-effectiveness analysis showed that the strategy of using apremilast before biologic therapy was dominant compared with the sequence of biologic treatments without apremilast. In addition, it is important to underline that the use of apremilast slightly increases the quality-adjusted life years gained over 5 years. Furthermore, within the budget impact analysis, the strategy including apremilast would lead to a saving of €16 million within 3 years. Savings would mainly be related to a reduction in pharmaceutical spending, hospital admissions and other drug administration-related costs.Conclusion: These models proved to be robust to variation in parameters and it suggested that the use of apremilast would lead to savings to the Italian healthcare system with potential benefits in terms of patients’ quality of life.

Real-World Insight on Apremilast Therapy in Patients with Plaque Psoriasis: Indian Experience.

Introduction:Psoriasis is an immune-mediated inflammatory skin disorder, which follows a chronic course. Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor, approved by US-FDA for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. A majority of the data related to the effectivity and safety of apremilast use in psoriasis is extracted from clinical trials. The present study was planned to get an insight into real-world experience with the use of apremilast in patients with moderate-to-severe plaque psoriasis related to its effectiveness and safety in India.Materials and Methods:The present study was a retrospective one, wherein a review of the medical records of patients with psoriasis was conducted at one center in Kolkata, who were prescribed apremilast for 16 weeks in a community dermatology practice, from December 2017 to May 2018.Results:Out of 39 patients, two patients discontinued treatment due to diarrhea. Only three patients were treatment naïve; the rest had taken some form of systemic therapy before apremilast. At the end of 16 weeks of treatment with apremilast, PASI 100 was achieved in one patient (2.7%), PASI 90 in one (2.7%), PASI 75 in 18 patients (48%), while 14 patients (38%) achieved PASI 50. Eighteen (46%) experienced adverse events, diarrhea being the most common (29.7%).Conclusion:The findings of the present study indicate that apremilast is effective in a real-world setting, as compared with clinical trials in achieving certain endpoints like PASI 75, as was found in other real-world studies in other countries, as well.

A cost-effectiveness and budget impact analysis of apremilast in patients with psoriatic arthritis in Italy

Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with psoriatic arthritis (PsA), within the Italian National Health Service (NHS).Methods: A Markov state transition cohort model, which was adapted to the Italian context, was used to compare the costs of the currently available treatments and of the patients’ quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for PsA in Italy, who can be eligible for treatment with apremilast. The eligible population was represented by adult patients with PsA who had an inadequate response to or were intolerant to previous disease-modifying antirheumatic drugs (DMARDs), for the approved indication, and for the treatment studied in the economic analytic model.Results: This cost-effectiveness analysis estimated that the strategy of using apremilast before biologic therapy is cost-effective, with an incremental cost-effectiveness ratio of €32,263.00 per QALY gained which is slightly over the normal threshold found in other Italian economic studies, which usually considers a 40-year-period. Conversely, the budget impact analysis was conducted over 3 years, and it led to an estimated annual saving of €1.6 million, €4.6 million and €5.5 million in the first, second and third year of apremilast commercialization, respectively, for a total saving of €11.75 million in 3 years.Limitations: Limitations of this analysis include the absence of head-to-head trials comparing therapies included in the economic model, the lack of comparative long-term data on treatment efficacy, and the assumption of complete independence between the considered response rates to therapy.Conclusion: The use of apremilast as a first option before the use of biologic agents may represent a cost-effective treatment strategy for patients with PsA who fail to respond to, or are intolerant to, previous DMARD therapy. In addition, based on a budget impact perspective, the use of apremilast may lead to cost savings to the Italian healthcare system.

Estudio Delphi para el uso de apremilast en la psoriasis

BackgroundExperience in the use of apremilast in clinical practice complements the information available from pivotal clinical trials. Material and methodFollowing a review of the literature, a panel of dermatologists with expertise in the management of psoriasis considered 5 scenarios in which the evidence supporting the use of apremilast to treat moderate psoriasis is insufficient or controversial. These scenarios were then assessed using a Delphi questionnaire. ResultsConsensus was reached on 96 (67%) of the 143 items (positive in 85 and negative in 11). The therapeutic goal for apremilast should be based on 4 outcomes: clinical response, symptoms, quality of life, and patient satisfaction. The scenario in which the use of apremilast was considered to have the greatest possibility of success was in patients with stable moderate psoriasis. Most of the clinicians considered apremilast to be an appropriate treatment when conventional therapies fail or are contraindicated, preferably before the prescription of biologic therapy. Consensus was reached that apremilast is an appropriate treatment for psoriasis in difficult locations, such as the scalp or the palms and soles. It was also agreed that apremilast requires less prescreening and monitoring than other conventional and biologic systemic therapies. ConclusionsApremilast could be a treatment option for patients with a different profile to that of clinical trial participants. The limitations of this proposal are the absence of consensus on the definition of moderate psoriasis, the lack of real-world evidence on the use of apremilast, and certain aspects related to tolerability.

Use of apremilast for the treatment of plaque psoriasis in a real world setting. The experience of a reference hospital in the Canary Islands

Use of apremilast for the treatment of plaque psoriasis in a real world setting. The experience of a reference hospital in the Canary Islands

Efficacy and safety of apremilast for Behçet's syndrome: a real-life single-centre Italian experience.

To evaluate the efficacy and safety of apremilast in treating oral ulcers (OUs), the cardinal and high-disabling feature of Behçet's disease (BD). Twelve consecutive patients affected by BD with recurrent/relapsing OUs resistant and/or intolerant to conventional therapy were enrolled and prospectively followed. The primary endpoint was the number of OUs at week 12. Secondary endpoints were modification from baseline to week 12 in Behçet's Syndrome Activity Score (BSAS), Behçet's Disease Current Activity Form (BDCAF) score, Behçet's Disease Quality of Life (BDQOL) scale and pain of OUs, as measured by a visual analogue scale (VAS). All adverse events (AEs) were recorded during follow-up. Non-parametric tests (Wilcoxon rank test) were used and a P-value <0.05 was considered statistically significant. After 12 weeks of apremilast, there was a significant reduction in the number of OUs [0.58 (s.d. 0.67) vs 3.33 (s.d. 1.45) at baseline, P = 0.02] that was paralleled by improvement in disease activity: BSAS was 16.8 (s.d. 9.1) [from 45.9 (s.d. 19.6) at baseline] (P = 0.02), BDCAF score was 0.72 (s.d. 0.65) [vs 2.45 (s.d. 1.0) at baseline] (P = 0.04) and the VAS score for pain decreased to 23.3 (s.d. 13.7) [vs 67.9 (s.d. 17.2) at baseline] (P = 0.02). Consistently, an improvement of BDQOL was assessed (P = 0.02). Clinical improvement led to complete steroid discontinuation in six patients and a tapering of the prednisone dose in two patients (P = 0.016). Colchicine was discontinued in six of nine patients (P = 0.031). AEs related to apremilast occurred in four patients (mainly due to gastrointestinal AEs), leading to drug discontinuation in all of them. Our preliminary real-world data support the use of apremilast as an effective therapeutic strategy against BD-related recurrent OUs resistant or intolerant to first-line therapy.

The Impact of Ramadan Fasting on the Reduction of PASI Score, in Moderate-To-Severe Psoriatic Patients: A Real-Life Multicenter Study.

Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the “Psoriasis Area and Severity Index” (PASI) score after the Ramadan fasting (mean difference = −0.89 ± 1.21, p < 0.0001) was found. At the multivariate regression, the use of cyclosporine (p = 0.0003), interleukin-17 or IL-17 blockers (p < 0.0001), and tumor necrosis factor or TNF blockers (p = 0.0107) was independently associated with a low PASI score, while the use of apremilast (p = 0.0009), and phototherapy (p = 0.0015) was associated with a high PASI score before the Ramadan fasting. Similarly, the consumption of cyclosporine (p < 0.0001), IL-17 blockers (p < 0.0001), mammalian target of rapamycin or mTOR inhibitors (p = 0.0081), and TNF blockers (p = 0.0017) predicted a low PASI score after the Ramadan fasting. By contrast, narrow band ultraviolet light B or NB-UVB (p = 0.0015) was associated with a high PASI score after Ramadan fasting. Disease duration (p = 0.0078), use of apremilast (p = 0.0005), and of mTOR inhibitors (p = 0.0034) were independent predictors of the reduction in the PASI score after the Ramadan fasting. These findings reflect the influence of dieting strategy, the biological clock, and circadian rhythm on the treatment of plaque psoriasis.

PSS15 - BUDGET IMPACT ANALYSIS OF APREMILAST IN PATIENTS WITH MODERATE-TO-SEVERE PLAQUE PSORIASIS IN GREECE

To assess the budget impact of increasing the use of apremilast in the management of adult patients with moderate-to-severe chronic plaque psoriasis (PsO), who have failed to respond to or have a contradiction to, or are intolerant to other systemic therapy from a Greek payer perspective. A 5-year (2018-2022) budget impact model was developed to estimate healthcare costs for adults with moderate-to-severe plaque PsO. Target population was defined based on epidemiological data, obtained from a local panel of experts and the literature. The population was divided into three categories; patients receiving conventional systemic therapy eligible to receive treatment with biologics or apremilast, patients currently treated with biologics or apremilast (switchers), and newly diagnosed patients eligible to receive treatment with biologics or apremilast (incidents). The analysis included all relevant currently reimbursed biologics (adalimumab, etanercept, infliximab, ustekinumab, secukinumab) and apremilast. Biosimilars for etanercept and infliximab were also included in the model. IMS (2017) prescription data were used for building up the market shares. Following a payer perspective, direct costs relating to drug acquisition and administration were considered (€, 2018). A total of 10,777 patients were estimated to receive biologics or apremilast in the first model year. Increased penetration of apremilast resulted in an estimated reduction of the total budget by 28.6%, leading to cost-savings of €31,606,416 over 5 years (€527,470,278 vs €495,863,863). Total costs per patient decreased by €2,374 over the same time period. The model yielded average annual cost-savings of 5.7% compared to the current treatment scenario. The sensitivity analyses confirmed the robustness of the model results. Increased use of apremilast for the treatment of moderate-to-severe plaque PsO represents a cost-saving strategy in the Greek healthcare setting.

Skin involvement in patients with psoriatic arthritis: preliminary results of treatment with apremilast in real world setting.

Apremilast is a "small molecule," an oral phosphodiesterase 4 inhibitor indicated for the twice-daily treatment of adults with psoriasis and psoriatic arthritis (PsA). Data concerning clinical experience in real world setting with apremilast for psoriasis are still exiguous, and aim of this report is to provide our experience in the use of apremilast in out-patient setting. Ten Caucasian individuals (6 male, 4 females; mean age 69,3; range 53-81 years) affected by moderate to severe plaque psoriasis (PASI≥10 e/o DLQI≥10 e/O BSA≥10) were treated with apremilast, following dosing regimen of technical data sheet and clinically evaluated both after 12 weeks (T12) and 16 weeks (T16). At baseline median PASI was 14 (range 10-25, SD 5.0). The median BSA was 17.55 (10-25, SD 6.0), the median PGA was 3.5 (2-5, SD 1.1), the median DLQI was 7.3 (5-18, SD 3.6). The median absolute value of PASI, BSA, PGA and DLQI showed a statistically significant decrease (P<0.05) already after 12 weeks of treatment. At T12, 6 patients out of 10 (60%) reached PASI 50 and 3/10 patients (30%) reached PASI 75. At T16, 9 patients out of 10 patients (9/10, 90%) reached PASI75, and 3/10 (30%) reached PASI90. Five patients out of 10 (50%) reached MDA at T16. Diarrhea was the main side effect occurring during the first weeks of treatment, that resolved spontaneously over the time. Although our preliminary results need to be confirmed by further larger observational studies, they seem to confirm the efficacy and safety profile provided through the ESTEEM registrative trials (ESTEEM 1-2).

Real-world use of apremilast for patients with psoriasis in Japan.

Apremilast is a novel oral phosphodiesterase 4 inhibitor effective for psoriasis. It regulates the production of pro-inflammatory mediators. Apremilast was approved in December 2016 in Japan; however, its efficacy and safety in a real-world setting among Japanese patients have not been reported. We report on 44 patients treated with apremilast between March and October 2017. The median treatment duration was 25 weeks (range, 2-33). Thirty-five patients (79.5%) continued the drug for at least 23 weeks, and five (11.4%) achieved a Psoriasis Area and Severity Index 100 response within 12 weeks. Nine patients discontinued the drug within 24 weeks mainly due to insufficient efficacy (n = 3) and adverse events (n = 4). Seven patients continued their previous systemic therapies such as cyclosporin (n = 1), methotrexate (n = 1), etretinate + methotrexate (n = 1) and biologics (n = 4) combined with apremilast. Of these patients, 55.9% had at least one adverse event although no severe adverse events. The most common adverse event was diarrhea (31.8%), followed by nausea (25.0%), headache (13.6%), abdominal discomfort (6.8%) and vomiting (6.8%). The proportion of diarrhea in our patients was higher than those of previous clinical trials. Among 10 patients with psoriatic arthritis, apremilast did not improve joint pain in nine (90%). To investigate the relationship between treatment efficacy and plaque size, we defined a small plaque as an individual rash diameter of 1 inch or less. The efficacy of apremilast was greater in patients with small plaques than in patients with large plaques.

The place of a phosphodiesterase 4 inhibitor in the treatment strategy for psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine, and entheses, which is associated with psoriasis. The pathological process is localized mainly in the tissues of the locomotor system and leads to the development of erosive arthritis and intra-articular osteolysis. PsA occurs in 5–7% of patients with moderate psoriasis. Despite advances in the treatment of psoriasis and PsA with diseasemodifying antirheumatic drugs (DMARDs) and biological agents (BAs), the problems associated with immunogenicity, infectious complications, and secondary inefficiency have not been fully solved. These factors have motivated the search for novel targeted synthetic drugs (signaling pathway inhibitors). This group of drugs includes apremilast, a phosphodiesterase 4 inhibitor. Recent data of controlled studies suggest that the drug is effective and safe in treating psoriasis and PsA. Prospects for the use of apremilast in PsA are associated with the possibility to use the drug in patients because of the inefficacy of DMARDs or BAs and with the ability to maintain long-term (more than 3-year) remission and to reduce the manifestations of enthesitis and dactylitis.

Signaling Рathway Blockers: Action Mechanism, Efficacy, Safety of Therapy for Patients with Psoriasis and Psoriatic Arthritis

In the literature review, contemporary data on immune pathogenesis of psoriasis and the emergence of comorbid states against the background of systemic chronic inflammation among patients is discussed. On the example of the apremilast medical preparation, the information on a new class of therapeutic agents for the treatment of psoriasis and psoriatic arthritis – “small molecules” is given, including their physicochemical properties and action mechanism, as well as on the key differences from immune-suppressive and genetically engineered biological preparations. Data on large-scale international randomised clinical trials of the efficacy and safety of the PDE4 inhibitor of apremilast among patients with moderate to severe psoriasis and psoriatic arthritis is presented. The published international clinical recommendations on the use of apremilast among patients with psoriasis and psoriatic arthritis, the criteria for evaluating the response to therapy, as well as the potential profile of patients for the use of apremilast in real clinical practice are discussed.

New insight into the pathogenesis of nail psoriasis and overview of treatment strategies.

Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population. The prevalence of nail involvement in psoriasis patients varies between 15% and 79%. While the nails represent a small portion of the body surface area, psoriasis in these areas can have a disproportionate influence on a patient’s physical and psychosocial activities. Differential diagnosis between an onychomycosis and a psoriatic nail could be challenging; nevertheless, coexistence of onychomycosis and nail psoriasis also occurs and both are common disorders in the general population. Nail psoriasis can be difficult to treat. Treatment of nail psoriasis should consider the body surface area of skin disease, psoriatic arthritis, severity of nail disease, and the impairment in the quality of life. All patients should be tested for onychomycosis before starting a therapy. This recommendation is underlined by the fact that nail psoriasis is mostly treated by immunosuppressive drugs, like steroids, methotrexate, or biologics, which may aggravate mycotic nail infections. Conventional systemic therapy, such as use of steroids, cyclosporine, methotrexate, and retinoid in the long term, can cause organ toxicities. Currently, use of apremilast and tofacitinib favors an early healing of nail psoriasis because they act directly on the pathogenic targets, distressing the inflammatory signals associated with the initiation and maintenance of the disease activity, and as with several conventional synthetic disease modifying antirheumatic drugs, they are characterized by the convenience of oral administration. The number of treatment options has increased considerably in recent years; however, given the heterogeneity of the disease, the therapy should be personalized to individual cases.

The Use of Apremilast to Treat Psoriasis During Deployment.

Psoriasis is a chronic immune-mediated dermatologic disorder affecting approximately 2% of the general population. Under current U.S. Army regulation, the diagnosis of psoriasis is a bar to enlistment or appointment and, if poorly controlled, is grounds for referral to a Medical Evaluation Board and potential discharge from military service, according to Army Regulation 40-501. However, between 2008 and 2015, over 3,600 soldiers sought care for psoriasis while deployed to combat theaters, indicating that psoriasis remains a significant medical concern in the U.S. military. Although mild psoriasis is treatable with topical agents, moderate to severe psoriasis may require systemic treatment. Prior to Food and Drug Administration approval of apremilast (Otezla) in 2014, the standard systemic treatment options were methotrexate and biologic agents such as anti-Tumor Necrosis Factor-alpha medications. Active use of methotrexate or biologic immunomodulatory medications automatically disqualifies soldiers from deployment due to monitoring requirements, the need for refrigeration, and the risk for immune compromise. Apremilast offers treatment efficacy similar to that of methotrexate, and it may be taken while deployed because it does not require monitoring or refrigeration. However, efficacy must be evaluated in the context of its much higher unit cost. Nonetheless, we argue that apremilast may be a useful treatment option for psoriasis in a select group of soldiers who must deploy despite suffering from moderate to severe psoriasis.

Apremilast for Lichen Planopilaris and Frontal Fibrosing Alopecia: A Case Series

Importance: Lichen planopilaris and frontal fibrosing alopecia are characterized by scarring alopecia associated with pruritus, inflammation, and pain of affected areas. There is a paucity of data on treatment options for these disorders. The available management options are associated with significant adverse effects and poor efficacy.Objective: To explore apremilast as a treatment option for refractory lichen planopilaris and frontal fibrosing alopeciaDesign: This is a retrospective case series analyzing the outcomes of four patients with refractory lichen planopilaris or frontal fibrosing alopecia treated with apremilast.Setting: The patients were seen in the faculty practice of an academic institution in New York City.Participants: Four female patients with biopsy confirmed lichen planopilaris or frontal fibrosing alopecia refractory to currently used treatmentsObservations: We report a case series of four patients with lichen planopilaris and frontal fibrosing alopecia who had failed multiple previous treatments, including intralesional steroids, anti-malarials, oral anti-inflammatory agents, minocycline, acitretin, mycophenolate mofetil, and laser treatment who responded to apremilast. While two of these patients discontinued the drug due to adverse effects such as gastrointestinal discomfort, clinical improvement was seen in every patient.Conclusions: To date, this is the first report of the use of apremilast for lichen planopilaris or frontal fibrosing alopecia, indicating its possible use in patients refractory to other treatments.

PDE4 Inhibition and Inflammatory Bowel Disease: A Novel Therapeutic Avenue.

Background. In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. However, in spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies. For these reasons there is an urgent need to look for new pharmacological targets. The novel Phosphodiesterase 4 (PDE4) inhibitors have been recently introduced as new modulators of intracellular signals and gene transcription for the treatment of IBD. Aim. To discuss and describe the state of the art of this new class of compounds in the IBD field, with particular attention to apremilast. Methods. Published articles selected from PubMed were comprehensively reviewed, with key words including apremilast, inflammatory disease, IBD, psoriasis, psoriatic arthritis, pathogenesis, therapies, and treatment. Results. PDE4 inhibitors generate elevated intracellular levels of cyclic Adenosine Monophosphate (cAMP), that consequently down-regulate the release of pro-inflammatory cytokines in the mucosa of IBD patients. The newly developed apremilast is one of these drugs and has already been approved for the treatment of dermatologic/rheumatologic inflammatory conditions; studies in psoriasis and psoriatic arthritis have in fact demonstrated its clinical activity. However, no clinical trials have yet been published on the use of apremilast in IBD. Conclusion. In light of the similarity of pro-inflammatory signaling pathways across the gut, the skin, and joints, apremilast is likely supposed to show its efficacy also in IBD.

Use of phosphodiesterase 4 inhibitor in patients with psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine, and entheses, which is associated with psoriasis. The pathological process is localized mainly in the tissues of the locomotor system and leads to the development of erosive arthritis, intra-articular osteolysis, and spondyloarthritis. Nonsteroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), biological agents (BAs), and targeted synthetic drugs (or signaling pathway blockers) are used to treat PsA. The latter group of drugs includes apremilast, a phosphodiesterase 4 inhibitor. Recent data of controlled studies suggest that apremilast is effective and safe in treating psoriasis and PsA. Prospects for the use of apremilast in PsA are associated with the possibility of giving the drug to patients because of the inefficacy of DMARDs or BAs.