- |||||||||| Zoryve foam (topical roflumilast foam) / Arcutis
Trial completion date, Trial initiation date, Trial primary completion date: The Safety and Efficacy of Roflumilast Foam in HS (clinicaltrials.gov) - Jul 9, 2026
P2, N=20, Recruiting,
Trial completion date: Dec 2028 --> May 2029 | Initiation date: Apr 2026 --> Sep 2026 | Trial primary completion date: Mar 2028 --> Aug 2028
- |||||||||| Review, Journal: Topical therapies for atopic dermatitis. (Pubmed Central) - May 29, 2026
US Food and Drug Administration-approved options include topical corticosteroids, calcineurin inhibitors, phosphodiesterase-4 inhibitors, a Janus kinase inhibitor, and an aryl hydrocarbon receptor agonist, each with different indications, efficacy, and safety considerations. Although most topical medications are studied as single agents compared with vehicle bases, in clinical practice, there is a broad set of approaches that might utilize multiple topical agents together or sequenced.
- |||||||||| roflumilast / Generic mfg.
Preclinical, Journal: Unveiling Remyelinating Properties of Roflumilast in CPZ-Induced Neuronal Demyelination in Mice. (Pubmed Central) - May 29, 2026
Remyelination was confirmed through Luxol fast blue staining, accompanied by reduced apoptotic marker, caspase-3, in oligodendrocytes. Collectively, these findings suggest that ROFL exerts neuroprotective effects and highlight the therapeutic potential of PDE-4 inhibition as a strategy for MS treatment.
- |||||||||| Choosing the Optimal Outcome Measure in Psoriatic Arthritis Clinical Trials () - May 23, 2026 - Abstract #EULAR2026EULAR_3639;
ACR50 and ACR70% responses achieved their maximum discriminative capacities at later study timepoints. The ACR20 response may therefore be preferrable as in trials with an early primary endpoint, while for endpoints beyond 6 months, ACR50 and 70 may be preferrable with comparable discrimination, yet higher clinical relevance.
- |||||||||| Comparative Efficacy and Safety of Biologics and Small Molecule Inhibitors in the Treatment of Moderate-to-Severe Psoriasis: A Systematic Review () - May 13, 2026 - Abstract #EADVSp2026EADV_Sp_1072;
inhibitors (Adalimumab, Etanercept)...Among small molecule inhibitors, Deucravacitinib was found to be more effective than Apremilast in achieving PASI 75 and Static Physician Global Assessment (sPGA) responses...Small molecule inhibitors like Deucravacitinib present promising alternatives, especially for patients seeking effective oral therapies. Further research is required to compare TYK2, JAK, and PDE4 inhibitors with IL-17 and IL-23 agents in head-to-head trials, to refine clinical treatment strategies for psoriasis.
- |||||||||| liraglutide / Generic mfg., roflumilast / Generic mfg.
Journal: Roflumilast Enhances Liraglutide's Atrial Natriuretic Peptide-Dependent Suppression of Adrenal Aldosterone Secretion. (Pubmed Central) - May 13, 2026
Taken together, these results suggest that roflumilast enhances the adrenocortical aldosterone suppression induced by GLP-1R agonists via cardiac GLP-1R/cAMP/Epac-dependent ANP secretion. Given the cardio-toxic effects of elevated aldosterone levels in the context of various heart diseases, such as post-myocardial infarction heart failure, combination of a GLP-1R agonist drug with a PDE4 inhibitor drug may be more advantageous than either agent alone in treatment of certain cardiovascular diseases.
- |||||||||| Eucrisa (crisaborole) / Pfizer
Journal: Pde4 mediates MHCII expression in oligodendroglia. (Pubmed Central) - May 5, 2026
In vivo modulation of the ISR with ISRIB or guanabenz bidirectionally controlled ImOL prevalence and stress-related behaviors. These findings position Pde4b-cAMP-ISR signaling as a regulator of oligodendroglial immune phenotypes and a promising target to modulate myelination and neuroinflammation in stress-related disorders.
- |||||||||| roflumilast / Generic mfg.
ROFLUMILAST DID NOT AUGMENT ANTIBODY-MEDIATED OPSONOPHAGOCYTOSIS AS MEASURED USING PNEUMOCOCCAL MOPA (Exhibition; Board-230) - Apr 14, 2026 - Abstract #ISPPD2026ISPPD_624;
We then performed MOPA on paired sera from 17 participants in a previous clinical trial of roflumilast: One sample collected from each participant before beginning the study drug, and the second was obtained at the follow-up study visit after beginning treatment with roflumilast.Results Opsonization index (OI) was similar for sera with and without preincubation of cells with roflumilast, and did not significantly differ between pre and post-roflumilast samples in the clinical trial (Figure 1). Conclusions While we cannot exclude the possibility of small changes in opsonophagocytic function, we did not find evidence that roflumilast substantially enhances antibody-mediated opsonophagocytosis measured using MOPA.
- |||||||||| apremilast / Generic mfg.
Retrospective data, Journal, Real-world evidence: Effectiveness of Apremilast in Patients With Palmoplantar Pustulosis: A 28-Week Real-World Study. (Pubmed Central) - Apr 13, 2026
These findings suggest that apremilast treatment is effective and tolerable for PPP patients requiring systemic treatment in routine practice. Further studies with larger cohorts and longer observation are required to confirm the sustainability of its clinical benefits.
- |||||||||| Review, Journal: Innovation in pediatric atopic dermatitis care: examining emerging topical treatment options. (Pubmed Central) - Apr 11, 2026
In recent years, novel topical agents with distinct mechanisms of action have expanded the therapeutic landscape, representing important steroid-sparing alternatives for children with AD. Emerging topical therapies for pediatric AD demonstrate substantial promise in addressing longstanding unmet needs, but long-term safety and practice-based effectiveness data remain critical for optimizing care.
- |||||||||| Journal: A fission yeast-based platform for nematode PDE inhibitor discovery. (Pubmed Central) - Apr 9, 2026
Finally, several of the most effective C. elegans PDE inhibitors were tested for their impact on C. elegans growth and fertility, two of which displayed toxic effects on C. elegans viability and fecundity using two different assessment methods, while a third showed a significant effect on fecundity. The strategy described herein offers an approach for discovery of novel anthelmintic and nematicidal compounds targeting parasitic nematode PDEs.
- |||||||||| Journal: cAMP and mitochondrial dysfunction in cancer cachexia. (Pubmed Central) - Apr 9, 2026
Both humans and mice with cancer cachexia display impaired 3',5'-cyclic adenosine monophosphate (cAMP)-protein kinase A-cAMP response element-binding protein 1 signaling, which leads to mitochondrial dysfunction. By rescuing this pathway with a phosphodiesterase-4 inhibitor, the authors highlight a potential therapeutic strategy for cancer cachexia.
- |||||||||| Jascayd (nerandomilast) / Boehringer Ingelheim, nintedanib / Generic mfg., pirfenidone / Generic mfg.
Review, Journal: Pathogenesis and immune regulation of rheumatoid arthritis-associated interstitial lung disease: from basic research to clinical implications. (Pubmed Central) - Apr 1, 2026
Additionally, emerging therapies like JAK inhibitors, CAR-T cells, and the upcoming phosphodiesterase-4B inhibitor, nerandomilast, show promise, but no curative treatment exists to date. Future research could focus on multi-omics technologies and conducting multicenter clinical trials to establish therapeutic targets and advance precision medicine for RA-ILD.
- |||||||||| Ohtuvayre (ensifentrine nebulized) / Merck (MSD)
Clinical, P3 data, Journal: Summary of Research: Ensifentrine, a Novel Phosphodiesterase (Pubmed Central) - Mar 25, 2026
It also reduced the rate and risk of flare-ups (called exacerbations) and was well tolerated. These results support the use of ensifentrine as an effective and well-tolerated treatment for people with COPD.
- |||||||||| irbesartan / Generic mfg., roflumilast / Generic mfg.
IRBESARTAN BUT NOT ROFLUMILAST AMELIORATES RENAL INJURY IN A COL4A5 R471* MUTANT MOUSE MODEL OF ALPORT SYNDROME AND CKD (Exhibition Hall/Poster Board No. P533) - Mar 19, 2026 - Abstract #ISNWCN2026ISN_WCN_2170;
Irbesartan exerted broad renoprotective effects, whereas roflumilast showed only limited impact on overall disease progression. These findings suggest that PDE4 inhibition alone is insufficient to confer renoprotection in Alport syndrome; however, it may hold potential as an adjunctive strategy when combined with renin
- |||||||||| Jascayd (nerandomilast) / Boehringer Ingelheim
A Phase III, Double-blind, Randomised, Placebo-controlled Trial Evaluating the Safety and Efficacy of Oral Nerandomilast Treatment on Halting Disease Progression in Systemic Sclerosis (Poster Tour IV) - Mar 17, 2026 - Abstract #EULAR2026EULAR_1930;
Patients will be stratified by SSc cutaneous subtype, presence of ILD on high-resolution computed tomography at randomisation, and concomitant use of mycophenolate, nintedanib, both or neither. Safety and tolerability of nerandomilast, mortality, pharmacokinetics and the effects of nerandomilast on different systemic organ manifestations of SSc, and on patients
- |||||||||| methotrexate / Generic mfg.
Review, Journal: Atopic Dermatitis. (Pubmed Central) - Mar 16, 2026
Systemic treatments include older off-label immunomodulators, such as methotrexate. Since 2017, multiple on-label injectable biologics and oral JAK inhibitors have been approved.
- |||||||||| paclitaxel / Generic mfg.
Journal: Target-Based Drug Delivery Approaches against Alzheimer's Disease - Recent Updates. (Pubmed Central) - Mar 15, 2026
The role of PDE4 in the coordination of cAMP response element-binding signaling in AD is also covered in this review. We highlight the advantages of specifically targeting PDE4D and discuss the use of herbal medications such as resveratrol, curcumin, 6-gingerol, and capsaicin, which are effective AD therapeutics and potential PDE4D inhibitors.
- |||||||||| Taltz (ixekizumab) / Eli Lilly, Cosentyx (secukinumab) / Novartis, apremilast / Generic mfg.
Journal: PDE4 inhibition in pediatric psoriasis: analysis of the SPROUT study on apremilast. (Pubmed Central) - Mar 15, 2026
Although the efficacy of apremilast is lower compared to modern biologics (e.g. secukinumab, ixekizumab), the drug offers unique practical advantages: oral administration, absence of pre-treatment screening for tuberculosis and chronic hepatitis, and no requirement for laboratory monitoring. With patent expiration and the arrival of generics, apremilast may represent a potential cost-effective 'first-line systemic' option for pediatric patients who are not candidates for or are reluctant to accept injectable therapies.
- |||||||||| Review, Journal: Dynamic changes of immune cells and therapeutic responses in experimental models of COPD. (Pubmed Central) - Mar 13, 2026
These findings highlight the importance of precision phenotyping and personalized immunomodulatory strategies. Overall, systematic elucidation of immune cell dynamics in COPD experimental models provides new insights into mechanisms of inflammation persistence and therapeutic responses, offering a theoretical basis for developing targeted interventions.
- |||||||||| Review, Journal: Inconsistent medication recommendations for immune-mediated inflammatory diseases across pregnancy, lactation, and paternal preconception: a guideline-based review. (Pubmed Central) - Mar 13, 2026
The lack of safety data in reproductive contexts contributed to guideline inconsistencies and revealed the need to prioritize future research on recently marketed pharmacotherapeutic classes, such as small molecules (JAK-inhibitors, PDE4-modulators) and interleukin inhibitors. In the future, guidelines should be updated regularly, include explicit recommendations, integrate reproductive contexts, and adopt unambiguous language, standardized categories and uniform methodological frameworks.
- |||||||||| roflumilast / Generic mfg.
Oral Roflumilast in Moderate-to-Severe Alopecia Areata: Potential Role in Patchy Disease () - Mar 12, 2026 - Abstract #AAD2026AAD_3982;
Phosphodiesterase-4 inhibitors (PDE4i) such as apremilast have shown inconsistent results, but roflumilast, a lower-cost PDE4i, has not been evaluated in this context...Six of 7 patients had previously received systemic therapy, most commonly corticosteroids or methotrexate...These preliminary findings suggest that roflumilast may represent a safe, cost-effective option for selected patients with patchy AA, while appearing ineffective in AU. Larger controlled studies are warranted to confirm these observations.
- |||||||||| Opzelura (ruxolitinib cream) / Incyte
Reassessing Long-Term Safety and Efficacy of Topical and Systemic Therapies in Atopic Dermatitis: An Updated Comparative Review () - Mar 12, 2026 - Abstract #AAD2026AAD_3925;
Despite these advances, the limited number of robust comparative studies and standardized criteria for transitioning between treatment classes continues to limit evidence-based decision-making. In the absence of large-scale clinical trials, network meta-analyses and expert consensus panels could be utilized to clarify long-term safety, refine sequencing strategies, and enhance the generalizability of treatment recommendations.
- |||||||||| methotrexate / Generic mfg.
Characterization of Psoriatic Arthritis Patients Managed in a Multidisciplinary Dermatology-Rheumatology Unit () - Mar 12, 2026 - Abstract #AAD2026AAD_3501;
Regarding treatment, 39.1% received anti-TNF drugs, 10.9% anti-IL-23, 13% anti-IL-17, and 4.3% anti-IL-12/23; 10.9% received PDE4 inhibitors, 15.2% methotrexate, 4.3% combinations, and 2.2% were untreated...This study highlights the heterogeneous clinical presentation of psoriatic arthritis. Patients are often referred late to multidisciplinary care, typically after many years of disease and unsuccessful systemic therapies, increasing the risk of irreversible joint damage.
- |||||||||| Jascayd (nerandomilast) / Boehringer Ingelheim, nintedanib / Generic mfg., pirfenidone / Generic mfg.
Clinical, Retrospective data, Review, Journal: Safety and Efficacy of Nerandomilast in Patients With Pulmonary Fibrosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (Pubmed Central) - Mar 11, 2026
Although a lower pooled risk of mortality was observed, individual trials were not powered for mortality outcomes, and event rates were low; therefore, this finding should be interpreted cautiously. Given the heterogeneity of pulmonary fibrosis phenotypes and trial designs, further large-scale RCTs should explore standardized outcomes, subgroup effects, and combination strategies with nintedanib or pirfenidone.
- |||||||||| hydroxychloroquine / Generic mfg., Eucrisa (crisaborole) / Pfizer
Journal: Treatment of discoid lupus erythematosus with crisaborole. (Pubmed Central) - Mar 11, 2026
Crisaborole, a topical phosphodiesterase-4 inhibitor approved for atopic dermatitis, may represent a well-tolerated nonsteroidal therapeutic option for facial DLE, particularly in patients who are unresponsive to or intolerant of conventional treatments. Further studies are needed to clarify its efficacy and long-term safety in DLE.
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