Apremilast In Psoriatic Arthritis Research Articles

Comparison between methotrexate and apremilast in Psoriatic Arthritis-a single blind randomized controlled trial (APREMEPsA study).

To compare the efficacy of methotrexate and apremilast in psoriatic arthritis (PsA). This Single blinded (physician), parallel group, randomized controlled trial was conducted at a single centre between October 2019 and December 2020. Adult PsA patients (age > 18years), fulfilling CASPAR criteria, not on methotrexate/apremilast in last 3months and never receiving bDMARDs or, JAK inhibitors, having active articular disease (one or more swollen joint or, having one or more tender entheseal point) were recruited. Primary outcome measure was rate of major cDAPSA response at week 24 and secondary outcome measures were ACR 20 response, change in PASI score, Maastricht enthesitis score, Leeds dactylitis index, and health assessment questionnaire-disability index (HAQ-DI) and number of adverse events at week 24 between methotrexate and apremilast groups. A total of 31 patients were recruited (15 in the apremilast arm and 16 in the methotrexate arm) amongst whom 26 patients completed 24weeks follow up (13 patients in the apremilast arm and 13 patients in the methotrexate arm). Median cDAPSA score at baseline was 23 (9) in the apremilast group and 20 (21) in the methotrexate group. No difference in major cDAPSA response at week 24 was observed between apremilast and methotrexate arm (20% vs. 37.5%; p = 0.433). In the secondary outcome measures, there was no significant differences between both the groups. Both the drugs were safe without any serious adverse events. There was no significant difference between methotrexate and apremilast in terms of efficacy as measured by cDAPSA and ACR20 responses.

An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022.

Since the early 1980s, phosphodiesterase 4 (PDE4) has been an attractive target for the treatment of inflammation-based diseases. Several scientific advancements, by both academia and pharmaceutical companies, have enabled the identification of many synthetic ligands for this target, along with the acquisition of precise information on biological requirements and linked therapeutic opportunities. The transition from pre-clinical to clinical phase was not easy for the majority of these compounds, mainly due to their significant side effects, and it took almost thirty years for a PDE4 inhibitor to become a drug i.e., Roflumilast, used in the clinics for the treatment of chronic obstructive pulmonary disease. Since then, three additional compounds have reached the market a few years later: Crisaborole for atopic dermatitis, Apremilast for psoriatic arthritis and Ibudilast for Krabbe disease. The aim of this review is to provide an overview of the compounds that have reached clinical trials in the last ten years, with a focus on those most recently developed for respiratory, skin and neurological disorders.

The Undeniable Benefits of Apremilast in Psoriatic Arthritis: An Observational Study from South India

Context: Ever since the introduction of apremilast in the Indian market in 2017, it was used in psoriatic arthritis with little information on the benefits of apremilast in this population, especially regarding the tolerability of the patients to tapered doses of apremilast. Aims: This study evaluates the efficacy, safety, and tolerability of apremilast in psoriatic arthritis. Settings and Design: A retrospective study was conducted on 120 patients aged ≥18 years who regularly visited one of the largest standalone rheumatology clinics between November 2018 and September 2019. Methods and Material: The proportion of patients who improved by 50% in their psoriasis area and severity index (PASI-50) score, as well as the reduction in tender joint count, swollen joint count, patient global health evaluation, and erythrocyte sedimentation rate, were all evaluated as effectiveness objectives. Statistical Analysis Used: The non-parametric test, Wilcoxon signed-rank test was used to compare between the baseline and follow-up measurements. Results: From a total of 120 patients, ninety-five patients showed a 65.09% reduction in the PASI score in the 16th week. A mean value for bath ankylosing spondylitis (BASDAI) of 4.36 at baseline was significantly reduced to 1.73 by the 16th week. Common adverse effects reported were gastritis (38.2%), diarrhea (32.4%), and fatigue (26.5%). Conclusions: Because of its tolerance and safety profile, apremilast may be regarded as a helpful medicine for the treatment of psoriatic arthritis, either alone or in combination with other medications, according to the findings of the study.

Expert recommendations for the use of apremilast in psoriatic arthritis

Introduction and objectivesDespite the evidence, there are doubts about the positioning of apremilast in the psoriatic arthritis (PsA) treatment algorithm. The objective of this project was to collect the scientific evidence and the experience of a group of rheumatologists who are experts in the management of PsA with apremilast in clinical practice in Spain. Material and methodsA scientific committee made up of 6 experts proposed 5 clinical scenarios where the evidence on the use of apremilast in PsA was controversial: (i) Efficacy in peripheral PsA; (ii) Efficacy in enthesitis and dactylitis; (iii) Efficacy in PsA with skin involvement; (iv) Comorbidities; and (v) Apremilast safety. After this, a panel of 17 rheumatologists with expertise in PsA management discussed these scenarios and generated a questionnaire with 50 questions and 156 items following the Delphi methodology. This questionnaire was anonymously answered by the panel. ResultsAfter 2 voting rounds, the panel of experts reached consensus in 93 of the 156 items raised (59.6%) (67 in agreement and 26 in disagreement). The degree of consensus was 53.3% in the area of “Efficacy in peripheral PsA”; 60.0% in “Efficacy in enthesitis and dactylitis”; 50.0% in “Efficacy in PsA with skin involvement”; 57.1% in “Management of comorbidities in patients with PsA”; and 67.3% in “Implications of safety in the use of apremilast”. ConclusionsThe structured opinion of the experts complements the available evidence and contributes to the establishment of consensual guidelines for the use of apremilast in PsA.

Long-term efficacy and safety of apremilast in psoriatic arthritis: Focus on skin manifestations and special populations.

Few real-life studies evaluated long-term apremilast therapy in the variable spectrum of clinical-anamnestic features which can be found in psoriatic arthritis (PsA) patients. This real-life retrospective observational study aimed to assess long-term efficacy, safety, and tolerability of apremilast among patients with PsA and concomitant cutaneous psoriasis. A stratified analysis was performed on special populations, defined as (a) number (≤1 vs >2) of comorbidities, presence or absence of: (b) history of malignancy, and (c) previous exposure to biologics. Patients attending three Italian University and Hospital centers, who received at least one dose of apremilast and had at least one follow-up visit were included. Ninety-six patients with PsA were identified. Psoriasis Area and Severity Index (PASI), Body Surface Area, 28-joint Disease Activity Score, and Dermatology Life Quality Index scores improved during treatment, already at week 4, relative to baseline. More than 2 comorbidities, history of malignancy and previous biologic treatment negatively influenced PASI responses. At least one adverse event was experienced by 56/96 patients, and 11/56 events required drug withdrawal. In conclusion, this study confirm efficacy and safety of apremilast on joints and skin involvement of PsA, highlighting which patients could have less favorable treatment response.

Apremilast generic for the treatment of active psoriatic arthritis: A single-center real-life experience from India

Introduction: Apremilast has been recently introduced in the treatment of adult psoriatic arthritis (PsA) patients in India. Its efficacy and safety have been established in the landmark clinical trials; however, there is still a dearth of its real-world experience in the management of PsA in India. Materials and Methods: A retrospective cohort analysis of electronic medical records was conducted at our clinic, to study the effectiveness and tolerability of apremilast 30 mg twice a day in the management of PsA. A total of 86 patients were included in this report. Patients were classified as responders and nonresponders based on the overall physician judgment of clinical status, especially improvement of symptoms as per the disease activity in PsA (DAPSA) criteria. Results: Of the 86 patients started on apremilast, 44 patients had at least 16 weeks of follow-up assessment. Of these 44 patients, 39 were of peripheral arthritis and five were of axial spondyloarthritis. Twenty-five of 39 (64%) patients were classified as responders and 14 (36%) as nonresponders based on the DAPSA criteria. On analyzing the DAPSA scores at baseline and subsequent follow-up, there was statistically significant improvement in mean DAPSA score. Remission was seen in three patients (7.7%) and low disease activity in 16 (41%) patients at 16 weeks. Only six patients developed one or more side effects. The most common side effects were gastrointestinal symptoms. Conclusion: These results, from a real-world setting in India, confirm the effectiveness and tolerability of apremilast in PsA as seen in clinical trials.

PBI14 COST-EFFECTIVENESS OF SECUKINUMAB VERSUS OTHER BIOLOGICS AND APREMILAST IN THE TREATMENT OF ACTIVE PSORIATIC ARTHRITIS: A SPANISH PERSPECTIVE

To assess the cost-effectiveness of secukinumab, an interleukin-17A inhibitor, with other biologics and apremilast in psoriatic arthritis (PsA) patients from a Spanish payers’ perspective. Secukinumab 150 mg and 300 mg were evaluated against etanercept, certolizumab pegol, adalimumab, golimumab, ustekinumab, infliximab, and apremilast over a lifetime horizon in a semi-Markov model. Both biologic-naïve (with or without moderate to severe psoriasis) and biologic-experienced PsA patients were considered. To assess treatment response, the 12-week PsA Response Criteria (PsARC) was used as a primary criterion. Model inputs were derived from PsA clinical trials, published literature, and other Spanish sources. Quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio were key model outcomes. Impact of input variations were evaluated through sensitivity analyses and alternative scenario analyses. Secukinumab 150 mg dominated all subcutaneous (S.C.) biologics and apremilast with highest QALYs of 9.22 and lowest lifetime cost of €192,445, while it was cost-effective against the intravenous (I.V.) infliximab in biologic-naïve patients without psoriasis. Among biologic-naïve patients with psoriasis and biologic-experienced patients, secukinumab 300 mg was cost-effective against all S.C. branded biologics and apremilast, while it dominated I.V. infliximab. PsARC response at 3-months, drug acquisition costs, and Health Assessment Questionnaire score change were identified as the most important parameters affecting model results as per one-way sensitivity analysis. Probabilistic sensitivity analysis showed maximum net monetary benefits with both secukinumab doses. Results from scenario analyses confirmed these results. Secukinumab is a cost-effective biologic treatment for PsA patients from a Spanish payer’s perspective.

Real-World Experience of Apremilast in Treating Psoriatic Arthritis Patients with Comorbidities

This observational study aimed to evaluate the efficacy and real-world experience of apremilast (APR) in treating psoriatic arthritis (PsA) patients with co-existing conditions presenting to clinic. Data from 28 patients treated with APR for PsA were collected between January 2016 and January 2019. Outcome measures disease activity score 44-C-reactive protein (DAS44-CRP), 0–68 for tender and 0–66 for swollen joint count, were collected at Weeks 0, 16, and 52. Response was classified using the Psoriatic Arthritis Response Criteria (PsARC). Adverse events or worsening of pre-existing conditions were recorded. Results included outcomes at Weeks 16 and 52 which showed a percentage reduction in mean DAS44-CRP at Weeks 16 and 52 by -1.4 and -1.9, respectively. There was percentage reduction at Weeks 16 and 52 of tender (-55.5%, -75.4%) and swollen (-45.8%, -61.5%) joint counts from baseline. It was also found that 19/28 (68.0%) patients were responders by PsARC criteria up to Week 52. Responders had shorter disease duration (mean: 4.9 years, standard deviation: 1.9) and lower previous exposure to biologic disease-modifying antirheumatic drugs (bDMARD); 16/19 subjects (84.0%) had no previous bDMARD. There were no serious adverse events during the study and no worsening of co-existing conditions during treatment. In this real-world observational study, APR was shown to be effective in PsA patients with multiple co-existing conditions. APR was more effective in PsA patients with shorter disease duration and in bDMARD naïve patients. APR provides another effective treatment option for PsA patients with multiple co-existing conditions.

Clinical experience with apremilast for psoriatic arthritis

The novel targeted synthetic disease-modifying antirheumatic drug apremilast (AP), a phosphodiesterase 4 inhibitor, is currently used to treat psoriasis and psoriatic arthritis (PsA). AP treatment can reduce the level of proinflammatory cytokines and the activity of inflammatory changes. The article describes a clinical observation of the efficacy of AP in PsA. It is demonstrated that AP used at a dose of 60 mg/day for moderate PsA activity leads to a reduction in the manifestations of peripheral arthritis, psoriasis (both during monotherapy and in combination with methotrexate), as well as to the achievement of low or minimal disease activity. It is shown that AP is generally well tolerated by patients.

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.

166 Long-term (156-week) improvements in dactylitis and enthesitis with apremilast inpsoriatic arthritis subjects: analysis of a large, pooled PALACE 1-3 database

166 Long-term (156-week) improvements in dactylitis and enthesitis with apremilast inpsoriatic arthritis subjects: analysis of a large, pooled PALACE 1-3 database

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.

Apremilast for psoriatic arthritis

Apremilast is a small molecule inhibitor of phosphodiesterase (PDE) 4 approved for the treatment of psoriatic arthritis (PsA). The efficacy and safety of apremilast in PsA have been demonstrated in four phase III trials. The compound has been approved for the treatment of moderate to severe PsA in the United States and in Europe. Apremilast also shows efficacy in psoriatic skin disease. Its mode of action is based on an increase of immune-regulatory cAMP in immune cells, which is mediated through the inhibition of the cAMP-degrading enzyme PDE4. Higher levels of cAMP inhibit cytokines involved in the pathogenesis of psoriasis, such as TNF-alpha or IL-23, resulting in clinical improvement.

Patient-reported Health-related Quality of Life with Apremilast for Psoriatic Arthritis: A Phase II, Randomized, Controlled Study

Apremilast, a specific inhibitor of phosphodiesterase 4, modulates proinflammatory and antiinflammatory cytokine production. A phase IIb randomized, controlled trial (RCT) evaluated the effect of apremilast on patient-reported outcomes (PRO) in psoriatic arthritis (PsA). In this 12-week RCT, patients with active disease (duration > 6 mo, ≥ 3 swollen and ≥ 3 tender joints) received apremilast (20 mg BID or 40 mg QD) or placebo. PRO included pain and global assessment of disease activity [visual analog scale (VAS)], Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Medical Outcomes Study Short-Form 36 Health Survey (SF-36) assessing health-related quality of life (HRQOL). Percentages of patients reporting improvements ≥ minimum clinically important differences (MCID) and correlations between SF-36 domains and pain VAS, HAQ-DI, and FACIT-F were determined. Among the 204 randomized patients (52.5% men; mean age 50.6 yrs), baseline SF-36 scores reflected large impairments in HRQOL. Apremilast 20 mg BID resulted in statistically significant and clinically meaningful improvements in physical and mental component summary scores and 7 and 6 SF-36 domains, respectively, compared with no change/deterioration in placebo group. Patients receiving apremilast 20 mg BID and 40 mg QD reported significant improvements ≥ MCID in global VAS scores and FACIT-F versus placebo, and significant improvements in pain VAS scores. Moderate-high, significant correlations were evident between SF-36 domains and other PRO. Apremilast resulted in statistically significant and clinically meaningful improvements in HRQOL, pain and global VAS, and FACIT-F scores.

Oral apremilast in the treatment of active psoriatic arthritis: Results of a multicenter, randomized, double‐blind, placebo‐controlled study

To evaluate the efficacy and safety of apremilast, a novel, orally available small molecule that specifically targets phosphodiesterase 4, in the treatment of active psoriatic arthritis (PsA). This phase II, multicenter, randomized, double-blind, placebo-controlled study included the following: a 12-week treatment phase, with patients receiving placebo, apremilast 20 mg twice per day, or apremilast 40 mg once per day; a 12-week treatment-extension phase, with patients in the placebo group re-randomized to receive apremilast; and a 4-week observational phase after treatment cessation. The primary end point was the proportion of patients achieving the American College of Rheumatology criteria for 20% improvement (ACR20) at week 12. Safety assessments included adverse events (AEs), physical examinations, vital signs, laboratory parameters, and electrocardiograms. Of the 204 patients with PsA who were randomized to a treatment group, 165 completed the treatment phase. At the end of the treatment phase (week 12), 43.5% of patients receiving apremilast 20 mg twice per day (P < 0.001) and 35.8% of those receiving 40 mg once per day (P = 0.002) achieved an ACR20 response, compared with 11.8% of those receiving placebo. At the end of the treatment-extension phase (week 24), >40% of patients in each group (patients receiving apremilast 20 mg twice per day, patients receiving apremilast 40 mg once per day, and patients in the placebo group re-randomized to receive apremilast) achieved the ACR20 level of improvement. Most patients in the treatment phase (84.3%) and treatment-extension phase (68.3%) reported ≥ 1 AE. Diarrhea, headache, nausea, fatigue, and nasopharyngitis were reported most frequently; most events were mild or moderate. No clinically relevant laboratory or electrocardiographic abnormalities were reported. Treatment with apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA. The balance of efficacy, tolerability, and safety supports further study of apremilast in PsA.