Daliresp (roflumilast) / AstraZeneca, Takeda, AbbVie - LARVOL DELTA

Successful treatment of lichen spinulosis with topical roflumilast: A case report. (PubMed, SAGE Open Med Case Rep) - "Topical roflumilast (0.3%) is a recently approved phosphodiesterase-4 inhibitor first used in psoriasis which has shown reduction in hyperkeratosis in vitro. We report on an adult with symptomatic and recalcitrant lichen spinulosis who achieved significant improvement with the use of topical roflumilast over a 6-month period."

Journal • Dermatology • Immunology • Psoriasis

Clinical and Economic Burden of COPD in Patients on Inhaled Triple Therapy in Germany - A Retrospective Claims Data Analysis. (PubMed, Int J Chron Obstruct Pulmon Dis) - "Escalation therapy with roflumilast, which is recommended in German guidelines, was prescribed to 3.1% of patients, of whom two-thirds discontinued the drug during the two-year follow-up. A substantial proportion of COPD patients initiating TT experience exacerbations resulting in high resource utilization and costs for the healthcare system. With poor treatment adherence and rare use of guideline-recommended escalation therapies, effective new treatments are needed to address the unmet medical need in this patient population."

HEOR • Journal • Retrospective data • Cardiovascular • Chronic Obstructive Pulmonary Disease • Immunology • Psychiatry • Pulmonary Disease • Respiratory Diseases

Phosphodiesterase-4 Inhibition: An Experimental Approach to Overcome Drug Resistance in a Rotenone-Corneal 6 Hz Kindling Mouse Model of Drug-Resistant Epilepsy. (PubMed, Mol Neurobiol) - "Standard anti-seizure medications (ASMs) such as pregabalin, levetiracetam, carbamazepine, phenytoin, and lamotrigine were used for resistance validation. Roflumilast as PDE4 inhibitor significantly manage DRE as evidenced by reducing seizure severity, improving cognitive functions and restoring neurochemical alterations. Its ability to modulate oxidative stress and provide neuroprotection in RCK mice underscores its promise as a novel adjunct treatment for DRE."

Journal • Preclinical • CNS Disorders • Epilepsy • Inflammation • CAT

Roflumilast mitigates idiopathic pulmonary fibrosis via inhibition of iron accumulation and ferroptosis. (PubMed, Eur J Pharmacol) - "Roflumilast activates CREB, thereby restoring iron homeostasis (by upregulating Slc40a1 and Fth1, while downregulating Tfrc. Additionally, it suppresses ferroptosis through the enhancement of GPX4 and FSP1, thereby ameliorating the progression of IPF. This dual targeting of iron homeostasis and lipid peroxidation underscores its therapeutic potential."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • AIFM2 • GPX4 • SLC40A1 • TGFB1

Role of PROs in HTA and Reimbursement Decisions Across UK, Germany, France, Italy, and Spain (ISPOR-EU 2025) - "In Germany, crizotinib's positive benefit rating was supported by robust PRO data (EORTC QLQ-C30, EQ-5D), while regorafenib's absence of robust PRO evidence downgraded its rating from "minor added benefit" to "no proven added benefit". UK's NICE cited PROs as pivotal in positive appraisals of pemetrexed and roflumilast, referencing significant improvements in symptom scales and quality-of-life...France's HAS rejected olaratumab and avelumab due to lack of robust PROs, but supported dupilumab and onasemnogene abeparvovec, where validated PROs and caregiver-reported outcomes strengthened value claims... PROs are increasingly integrated into HTA submissions across EU4 + UK, yet their impact on reimbursement varies. Methodological rigor, validated instruments, and disease context remain critical for influencing positive decisions."

Reimbursement • US reimbursement • Rheumatology

Roflumilast as an Emerging Treatment for Oral Lichen Planus: A Case Series (ISDS 2025) - "Management typically relies on off-label medications such as topical corticosteroids (TCS), systemic corticosteroids, calcineurin inhibitors (TCI), oral retinoids, and cyclosporine. Phosphodiesterase-4 (PDE-4) inhibitors, including apremilast and roflumilast, have recently been explored for OLP...Case Series: We present three cases of OLP in patients aged 65, 66, and 69, each with recurrent flares after multiple prior therapies, including TCS, TCI, hydroxychloroquine, and minoxidil...Adjunctive therapy included isotretinoin in two cases and topical tacrolimus swish and spit in the third case... This case series suggests that OR may be an effective treatment option for OLP. Further studies are warranted, as only one prior investigation of OR in OLP exists."

Clinical • Anorexia • Dermatitis • Dermatology • Dermatopathology • Gastrointestinal Disorder • Immunology • Inflammation • Lichen Planus • Movement Disorders • Mucositis • Pruritus • CD8

PDE-4 Inhibition in Sarcoidosis Patients: A Retrospective Single-Center Analysis of 51 Patients. (PubMed, Pharmaceuticals (Basel)) - " Sarcoidosis patients receiving Roflumilast had less lung function loss and were less likely to require therapy escalation. Roflumilast could be a therapeutic option in sarcoidosis."

Journal • Retrospective data • Chronic Obstructive Pulmonary Disease • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Sarcoidosis

Efficacy and Safety of Roflumilast versus Alpha-Lipoic Acid in Type 2 Diabetes with Neuropathy: A Comparative Clinical Study. (PubMed, Diabetes Metab Syndr Obes) - P3 | "Roflumilast may offer superior glycemic and oxidative stress control benefits, though neuropathy symptoms control was comparable to ALA. (NCT05369793)."

Journal • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Neuralgia • Oncology • Pain • Type 2 Diabetes Mellitus • NTS • TNFA

PSOROFLU: A Pilot Study to Assess How Safe and Effective Oral Roflumilast is for Treating Moderate to Severe Psoriasis in Adults (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Ahmed Ibrahim

New P2 trial • Dermatology • Immunology • Psoriasis

Anti-oxidative and anti-inflammatory effects of the phosphodiesterase 3/4 inhibitor ensifentrine. (PubMed, Int Immunopharmacol) - "Peripheral blood mononuclear cells (PBMCs) from COPD patients and healthy controls and human bronchial epithelial cells were treated with ensifentrine or a PDE4 inhibitor (roflumilast or GSK256066) or dexamethasone prior to exposure to lipopolysaccharide or T-cell receptor activation, with measurement of supernatant levels of TNFα and IFNγ, respectively. We report a novel mechanism of action for ensifentrine, reducing effects of oxidative stress through a PDE3 dependent mechanism. The anti-inflammatory effects of ensifentrine were lower compared to the PDE4 inhibitors tested."

IO biomarker • Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CASP3 • CASP7 • IFNG • TNFA

Repositioning Triazoles as Phosphodiesterase-4 Inhibitors to Suppress COVID-19 Cytokine Storms and Fungal Co-Infections via Docking and Simulation. (PubMed, J Cell Mol Med) - "This study aimed to investigate the off-target potential of commonly used antifungal triazoles itraconazole, ketoconazole, posaconazole and voriconazole against human phosphodiesterase-4 (PDE-4), a key enzyme involved in the regulation of pro-inflammatory cytokine expression...Binding affinity and interaction stability were compared with roflumilast, a known PDE-4 inhibitor...Quantum chemical analysis indicated strong electrophilicity and reactivity of posaconazole, supporting its potential PDE-4 inhibitory activity. The findings suggest that certain triazole antifungals, especially posaconazole, may both fight fungal infections and reduce the cytokine storm in severe COVID-19, offering a promising rapid-response therapeutic strategy."

Journal • Infectious Disease • Novel Coronavirus Disease

Targeted Inhibition of Phosphodiesterase (PDE) 4 As a Novel Therapy to Increase Endothelial Cell cAMP and Trigger Weibel Palade Body Exocytosis (ASH 2023) - "In contrast, selective PDE-4 inhibition with Roflumilast (ROF) resulted in a dose-dependent increase in VWF:Ag secretion in both HUVEC (1.51 fold, p<0.0001, Fig.1) and HMVEC-L (1.75 fold, p=0.007). Moreover, we demonstrate that ROF stimulates VWF release in vitro without deleterious effects on platelet aggregation. Our data highlight the therapeutic potential of PDE-4 inhibitors, either alone or in combination with DDAVP, in the treatment of VWD."

Chronic Obstructive Pulmonary Disease • Dermatology • Hematological Disorders • Immunology • Psoriasis • Pulmonary Disease • Respiratory Diseases

Roflumilast in dermatology: Revolutionizing inflammatory skin treatment. (PubMed, Indian J Pharmacol) - No abstract available

Journal • Dermatology

Purine-2,6-dione-based multitarget-directed ligands inhibiting PDE/TRPA1/CHIT1 as a new approach for the treatment of COPD. (PubMed, Bioorg Chem) - "Moreover, ligands 39 and 47 demonstrated more potent bronchodilatory effects ex vivo, surpassing theophylline and roflumilast...This compound also reduced the level of the NLRP3 inflammasome multiprotein complex, thereby inhibiting its activation and reducing NF-κB phosphorylation. In summary, the data obtained in this study suggest that the innovative, multifunctional activity of compound 39 (as confirmed by molecular modeling studies predicting its binding mode) may represent a promising new strategy for the treatment of COPD."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • ELANE • NLRP3 • TRPA1

Design and development of potent roflumilast analogues targeting PDE-4B: selectivity and pharmacokinetic insights. (PubMed, Bioorg Chem) - "Equilibrium dialysis technique revealed that compound 4i had plasma protein binding comparable to roflumilast (93.01 % vs. 94.80 %), whereas 4f showed the lowest binding percentage at 77.24 %, indicating better accessibility for tissue distribution. Overall, this work highlights selective PDE-4B inhibitors as a compelling direction for future COPD therapies."

Journal • PK/PD data • Cardiovascular • Chronic Obstructive Pulmonary Disease • CNS Disorders • Immunology • Oncology • Psychiatry • Pulmonary Disease • Respiratory Diseases • Schizophrenia

1118: COPD Management: Advanced Pharmacological Options (CHEST 2025) - "This session will address medication class selection in COPD highlighting considerations for newly approved options (ensifentrine and dupilumab) and how they fit in with existing therapies. Review the evidence for ensifentrine, roflumilast, and azithromycin and provide a framework for drug selection 3. Learn about the currently available and emerging biologic therapeutics in the management of COPD"

Metastases • Chronic Obstructive Pulmonary Disease • Eosinophilia • Immunology • Respiratory Diseases

APPROACH TO A GROWING LANDSCAPE OF PHARMACOLOGIC THERAPIES FOR COPD PATIENTS WITH HIGH EXACERBATION RISK (CHEST 2025) - "It has been shown that ensifentrine, dupilumab, long-term azithromycin, and roflumilast all help to reduce exacerbations in patients prone COPD exacerbations 1 . Ensifentrine or dupilumab was an appropriate choice for over half of this cohort; these medications have expanded the options for treating Group E COPD patients at risk for recurrent exacerbations. With a growing landscape of pharmacologic options to help reduce the risk of COPD exacerbations, it is important for patients with high exacerbation risk be continually evaluated for additional therapies. Based on the data from this cohort, the majority of patients hospitalized due AECOPD would benefit from an additional pharmacologic agent with their optimized inhaled therapies."

Clinical • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

COMPARISON OF EFFECTS BETWEEN ROFLUMILAST AND AZITHROMYCIN IN MANAGEMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (CHEST 2025) - "Patients with history of asthma, bronchiectasis, HIV, transplantation, tuberculosis or use of dupilumab were excluded. Roflumilast was associated with a significantly lower risk of exacerbations at one year compared to chronic azithromycin use. There was an almost threefold increase in all-cause mortality in the roflumilast cohort compared to the azithromycin cohort. While roflumilast was associated with a lower incidence of pneumonia, rates of oxygen dependence were comparable between the two treatment groups."

Asthma • Bronchiectasis • Cardiovascular • Chronic Obstructive Pulmonary Disease • Human Immunodeficiency Virus • Immunology • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A 52-week, Placebo- and Active- Controlled (Roflumilast, Daliresp® 500µg) Study to Evaluate the Efficacy and Safety of Two Doses of CHF6001 DPI (Tanimilast) as add-on to Maintenance Triple Therapy in Subjects With COPD and Chronic Bronchitis. (PILLAR) (clinicaltrials.gov) - P3 | N=3973 | Active, not recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2027 ➔ Dec 2025 | Trial primary completion date: Apr 2027 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

PDE4-Selective Inhibition in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Different Agents or Different Targets? (PubMed, Life (Basel)) - "Highly selective inhibitors of the members of the cAMP-selective cyclic nucleotide phosphodiesterases, or PDE4 family, have shown clinically meaningful activity in two different classes of lung disease: roflumilast in obstructive lung disease, specifically chronic obstructive pulmonary disease (COPD), and nerandomilast in restrictive lung diseases characterized by inflammation/fibrosis of the alveolar interstitium, including idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF)...The emerging data are compatible with PDE4-selective inhibitors having targets of action in a large number of pulmonary cell types, only a subset of which is dysregulated in either COPD or IPF. This suggests that differences between the benefits observed with these individual agents in their various clinical indications reflect differences in disease pathogenesis, rather than proven differences in the enzyme-inhibitory effects of the various PDE4 inhibitors that have been..."

Journal • Review • Chronic Obstructive Pulmonary Disease • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Seborrheic Dermatitis Revisited: Pathophysiology, Diagnosis, and Emerging Therapies-A Narrative Review. (PubMed, Biomedicines) - "However, new therapeutic approaches are under investigation, including PDE4 inhibitors (roflumilast, crisaborole, and apremilast), topical and oral JAK inhibitors, probiotics, and microbiome-targeted therapies. SD remains a challenging condition due to its relapsing course and limited long-term therapeutic options. Emerging therapies represent a valuable opportunity to address unmet clinical needs, particularly in patients with severe, recurrent, or treatment-resistant forms."

Journal • Review • Dermatitis • Dermatology • Immunology • Inflammation • Seborrheic Dermatitis

COMPARATIVE OUTCOMES OF AZITHROMYCIN VS AZITHROMYCIN AND ROFLUMILAST IN ADVANCED COPD: A MULTICENTER RETROSPECTIVE ANALYSIS (CHEST 2025) - "This study suggests a modest survival benefit with combination therapy but highlights increased risks of pulmonary hypertension and serious infections, including sepsis and pneumonia. While non-significant trends in cardiovascular outcomes and pulmonary embolism were observed, the findings highlight the need for careful patient selection and monitoring. Further prospective studies are necessary to optimize treatment strategies in advanced COPD."

Metastases • Retrospective data • Atrial Fibrillation • Cardiovascular • Chronic Obstructive Pulmonary Disease • Heart Failure • Immunology • Infectious Disease • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Embolism • Respiratory Diseases • Septic Shock • Ventricular Tachycardia

PREVENTING CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXACERBATION READMISSIONS: UTILIZING COPD NAVIGATORS (CHEST 2025) - "Data collection included demographics, Charlson Comorbidity Index (CCI), admission eosinophil count, FEV1, admission pCO2, smoking status, concomitant viral infection, pulmonary clinic follow-ups, length of stay, NIPPV at discharge, supplemental oxygen at discharge, ICU admittance, prescription for azithromycin or roflumilast at discharge, and 90-day mortality. The preliminary data suggests that 30-day readmission is correlated with increased long-term oxygen use, increased NIPPV use inpatient and discharge, increased 90-day mortality, and length of stay. CLINICAL IMPLICATIONS: Prioritizing interventions centered around oxygen usage and NIPPV may help reduce COPD readmissions."

Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tobacco Cessation

Identification of a novel PDE4 inhibitor inspired by leoligin-derived lignans. (PubMed, Eur J Med Chem) - "Marketed PDE4 inhibitors, such as roflumilast and apremilast, treat chronic obstructive pulmonary disease and psoriasis. Lastly, a functional study was conducted in LPS-activated macrophages, where LT-104A reduced nitric oxide release and decreased mRNA expression of Il1b and Nos2. In conclusion, extensive in vitro screening of leoligin analogues led to the identification and characterisation of a novel PDE4 inhibitor, LT-104A, with potential in vitro anti-inflammatory properties."

Journal • Chronic Obstructive Pulmonary Disease • Dermatology • Immunology • Psoriasis • Pulmonary Disease • Respiratory Diseases • IL1B • NOS2

Effects of Roflumilast on Exacerbations and Lung Function in COPD Patients with Bronchiectasis. (PubMed, Chonnam Med J) - "While roflumilast improved pulmonary function and symptoms in COPD patients with bronchiectasis, it was also linked to a higher risk of exacerbations. These findings suggest caution in its use for this population, and further randomized controlled trials are needed to assess its safety and efficacy."

Journal • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases