Search Results (33)

Approximately 3–13% of patients with psoriasis are first affected after age 60 years. Numerous studies have investigated the use of biologic agents for the treatment of psoriasis, but the routine exclusion of elderly adults from clinical trials has limited our knowledge about their effects in this age group. Background/Objectives: This study aimed to investigate the efficacy and safety of biologic drugs for the treatment of psoriasis in elderly patients. Methods: A single-center-based retrospective cohort study design was used. A total of 149 elderly patients with psoriasis were divided into two groups by age at initiation of biologic treatment: <65 years (adult-start group) and >65 years (elderly-start group). Data on patient characteristics were collected and analyzed, and drug survival was evaluated. Results: Demographics, comorbidities, and treatment turnover were similar in the adult-start and elderly-start groups. Drug survival of adalimumab as first-line treatment, and of guselkumab in any treatment sequence, was significantly better in the elderly-start group (p = 0.029 and p = 0.032, respectively). There was no between-group difference in drug safety, as reflected in hospitalizations for infection or death. Conclusions: Biologic treatments for psoriasis demonstrate both efficacy and safety in elderly patients. Some agents exhibited better drug survival when initiated after age 65 years. Full article

Interleukin-23 (IL-23) is a key cytokine involved in the pathogenesis of various immuno-mediated inflammatory diseases. In recent years, several drugs selectively targeting IL-23 have been developed and three of them (mirikizumab, risankizumab and guselkumab) were successfully investigated in clinical trials for ulcerative colitis (UC). All of them showed a good profile for efficacy, alleviating symptoms, and inducing endoscopic and histologic improvement, with very low incidence of adverse events. Bowel urgency also emerged as a crucial outcome from patients’ perspective in the mirikizumab trials. The correct positioning of IL-23 inhibitors in the therapeutic algorithm for UC represents a new challenge for physicians, especially because it is not guided by biomarkers or predictors of effectiveness. Moreover, no comparative clinical data exist among the available IL-23 inhibitors, although molecular differences might potentially impact their effectiveness. A role for IL-23-inhibitors may also lie in combination with drugs with different mechanisms of action for complex, multi-refractory patients. This review, focusing on UC, summarizes all the clinical data available on IL-23 inhibitors and provides a perspective on the best clinical scenarios to maximize their effectiveness. Full article

Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3–44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1–1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10–10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1–1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1–1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients. Full article

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterized by recurrent pustules, erythema, and scaling on the palms and soles, leading to a significantly reduced quality of life. Although PPP shares some immunopathological features with psoriasis vulgaris, it is distinguished by unique genetic predispositions, including a higher prevalence in East Asian populations, and a complex immune profile, particularly dysregulation of the IL-23/Th17 axis and IL-36 cytokines. Recent advances in psoriasis treatment have highlighted IL-23 inhibitors, which target the p19 subunit to suppress Th17 activation and inflammatory cytokines. Clinical trials show that IL-23 inhibitors significantly improve disease severity and patient-reported outcomes in PPP while maintaining favorable safety profiles. Notably, guselkumab and risankizumab have recently been approved for PPP treatment in Japan and Korea. In contrast, IL-17 inhibitors and IL-36 blockers have yielded mixed results. A recent phase 3 trial in Japan demonstrated the significant efficacy of apremilast in treating PPP, with a favorable safety profile, suggesting that apremilast may be a promising treatment option for PPP. Due to PPP’s lower prevalence compared with psoriasis vulgaris, clinical trials remain limited. Further large-scale, controlled studies are needed to clarify the efficacy and long-term safety of these therapies in diverse populations. This review summarizes emerging evidence on IL-23 inhibitors and other treatments for PPP, detailing their mechanisms of action, clinical efficacy, safety profiles, current challenges, and future perspectives in optimizing therapy. Full article

Background: Axial involvement in psoriatic arthritis (axPsA) presents clinical and radiological differences from ankylosing spondylitis (AS), which may influence the therapeutic response. While Guselkumab has demonstrated efficacy in peripheral PsA, its role in axPsA is less well established, particularly in real-world settings. Objective: To evaluate the positive effects of Guselkumab therapy in patients with psoriatic arthritis (PsA), 58.6% of whom have axial involvement, in a 12-month, single-center, longitudinal, prospective observational cohort study conducted in a real-life setting. Methods: A cohort of 99 patients with PsA, including 58 with axial involvement (axPsA), was treated with Guselkumab for 12 months. Treatment efficacy was assessed by evaluating the reduction in mBASDAI, ASDAS, DAPSA, VAS Pain, LEI, and HAQ scores. The Friedman test was used to analyze whether the overall changes from baseline to 12 months were statistically significant. Patients with axial involvement were assessed by MRI, with scores measured at baseline (t₀), after 6 months (t₆), and after 12 months (t₁₂) of therapy. Statistical evaluation was conducted using the Friedman test, followed by pairwise comparisons of values obtained at different follow-up time points using the Wilcoxon signed-rank test. Additionally, the drug’s retention rate was examined using a Kaplan–Meier curve. Results: After 12 months of therapy, a statistically significant reduction was observed in all clinimetric parameters. Patients with axial involvement were also evaluated by MRI at baseline, after 6 months, and after 12 months of therapy. MRI images showed a reduction in bone marrow edema and a decrease in signal intensity, indicating a significant reduction in inflammation and confirming the drug’s efficacy. Retention rate values demonstrate that Guselkumab is well tolerated and effective in the long term for the majority of patients. Conclusions: This 12-month real-world study of 99 PsA patients confirms the efficacy of Guselkumab in reducing disease activity in both peripheral and axial forms. The findings align with previous RWE and clinical trials (DISCOVER-1 and -2), supporting its clinical utility in PsA and axPsA, with high treatment retention. Full article

Psoriasis is an immune-related disorder that is marked by abnormal thickening of the skin, the rapid multiplication of keratinocytes, and complex interactions between immune cells and the affected areas. Although psoriasis cannot currently be cured, drugs can alleviate symptoms by regulating immune homeostasis and preventing comorbidities. There are many types of drugs to treat psoriasis: small-molecule drugs, including corticosteroids; retinoids; vitamin D analogs; and immunosuppressants, such as glucocorticoid ointment, tretinoin cream, methotrexate tablets, etc. Macromolecular biological drugs, such as Certolizumab, Secukinumab, Guselkumab, etc., include monoclonal antibodies that target various inflammatory signaling pathways. Compared with traditional small-molecule drugs, biological therapies offer better targeting and lower systemic side effects, but their high costs and invasive administration modes constrict their widespread use. Spesolimab is the latest biological agent used to target the interleukin-36 receptor (IL-36R) to be approved for market use, which significantly reduces the risk of general pustular psoriasis (GPP) flare by 84%. Additionally, there are several biological agents used to target the interleukin-23/T helper 17 cell pathway that have already entered Phase II and III clinical trials. At present, the first-line therapeutic strategy for mild psoriasis is topical administration. Systemic therapy and phototherapy are preferred for treating moderate to severe types. However, the current therapeutic drugs for psoriasis cannot completely meet the clinical needs. More advanced drug delivery systems with optimized target effects and better bioavailability are required. Nanocarriers are emerging for the delivery of proteins, nucleic acids, and cell-based therapies. In this review, we analyze the current status of psoriasis therapeutics and discuss novel delivery systems for diverse psoriasis drugs, as well as emerging cell-based therapies. We also summarize the therapeutic effectiveness of different delivery strategies. Full article

Crohn’s disease (CD) is a chronic inflammatory condition of the digestive tract, driven by an imbalance in immune system regulation, where proinflammatory interleukin-23 (IL-23) plays an essential role. Selective new IL-23 inhibitors, including risankizumab, guselkumab, and mirikizumab, block the IL-23p19 subunit to inhibit the Il-23 action and alleviate inflammation in CD. This review explores the effectiveness, safety, and therapeutic potential of anti-IL-23 treatment in CD management. Risankizumab, guselkumab, and mirikizumab demonstrated considerable effectiveness in inducing clinical remission and promoting endoscopic healing in patients with moderately to severely active CD, including those refractory to anti-TNF therapies. Risankizumab showed favorable results in pivotal trials like ADVANCE, MOTIVATE, and FORTIFY, achieving remission rates of up to 45% and sustained inflammatory biomarkers normalization. Guselkumab and mirikizumab similarly demonstrated substantial efficacy in the induction and maintenance phases, with promising long-term results. The safety profiles of IL-23 inhibitors were favorable, with low rates of serious adverse events, including infections and malignancies. Selective new IL-23 inhibitors represent a targeted and effective therapeutic class for moderately to severely active CD, offering high clinical and endoscopic remission rates, and favorable safety outcomes. Continued research, particularly on long-term efficacy and the selection of patients based on inflammatory biomarkers, will help optimize their role in personalized treatment strategies for refractory CD. Full article

Background/Objectives: Inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions requiring long-term therapy to maintain remission and improve quality of life. Despite the approval of numerous drugs, IBD continues to present treatment challenges. This review aims to summarize novel therapeutic target agents in phases II and III of development, including sphingosine-1-phosphate receptor modulators (S1P), anti-interleukin-23 (IL-23), and other small molecules and monoclonal antibodies currently under investigation (e.g., anti-TL1A, obefazimod, NX-13, RIPK-inhibitors). Methods: A comprehensive literature search was conducted up to December 2024 to identify relevant articles published in English over the past three–five years, focusing on phase II/III studies for UC and CD. The search included databases such as PubMed, Google Scholar, and the ClinicalTrials.gov portal. Results: Clinical trials underline the potential of novel immunomodulators, including anti-TL1A, obefazimod, NX-13, RIPK inhibitors, and anti-IL-23p19 agents, as promising therapeutic options for IBD. Anti-IL23p19 therapies, such as risankizumab and mirikizumab, alongside guselkumab, exemplify this class’s growing clinical relevance. While some are already in clinical use, others are nearing approval. Conclusions: Ongoing research into long-term safety and the development of personalized treatment strategies remains pivotal to enhance outcomes. Patient stratification and the strategic positioning of these therapies within the expanding treatment landscape are critical for optimizing their clinical impact. Full article

Objectives: This study is a retrospective analysis of patients with plaque psoriasis treated with biological drugs at a single center in Poland. We sought to evaluate patient demographics, disease characteristics, comorbidity burden, and treatment patterns in this cohort. Methods: Data were collected from the medical records of patients with plaque psoriasis who received biological treatments. In total, data from 1 January 2013 to 2 August 2024 were analyzed, encompassing 159 patients. The variables analyzed included age, disease duration, affected areas, prior treatments, and treatment outcomes. Results: The mean age at the start of biological treatment was 48 years (range: 10–73 years), with an average psoriasis duration of 18.2 years (range: 1–51 years). Obesity was noted in 39% of patients. Psoriasis lesions commonly affected the scalp (74.66%) and nails (64.38%). Methotrexate was the most commonly used systemic therapy prior to biologics (86.30%). Risankizumab and adalimumab were the most frequently prescribed biologics. Secondary treatment failure led to the highest discontinuation rates with tildrakizumab, whereas bimekizumab, guselkumab, risankizumab, and secukinumab showed the lowest rates. Conclusions: Biological drugs play a pivotal role in managing plaque psoriasis, particularly for patients with comorbidities and in treating challenging areas such as the scalp and nails. Risankizumab and adalimumab were prominent in prescription patterns. Future research involving larger cohorts and prospective designs is needed to deepen understanding and optimize treatment strategies for plaque psoriasis in Poland. Full article

Background: The treatment of psoriasis has made considerable progress with biologicals, including tumor necrosis factor inhibitors, and recently, monoclonal antibodies inhibiting directly interleukin (IL) 17, IL-23, or both IL-12/23. Newer biologicals are directed to the interleukin pathway and appear to improve complete or near-complete clearance. The newer biologicals have also been shown to have an excellent safety profile. However, despite experience with patients having confirmed the results obtained in clinical trials, there are still few data on using the newer biologicals. Methods: The present active study aimed to prospectively evaluate safety profiles and persistence of some biologicals in a multicenter pharmacovigilance study, that enrolled 733 patients treated with a biologic drug in five Calabrian hospital units. Informative and treatment persistence evaluations with predictors for suspension and occurrence of adverse events (AEs) were executed. In particular, reasons for treatment discontinuation in our program take account of primary/secondary failure or development of an AE. Results: AEs occurred in 187/733 patients and serious AEs (SAEs) were identified in 5/733 patients. An number of 182/733 patients showed a primary/secondary inefficacy. The AEs and SAEs were described with adalimumab, infliximab, and etanercept but not with abatacept, brodalumab, tildrakizumab, golinumab, ixekizumab, guselkumab, risankizumab, secukinumab, and ustekinumab. Conclusions: Our analysis, although limited by a small sample size and a short-term follow-up period, offers suitable data on commonly used biological agents and their safety, interruption rate, and the attendance of SAEs. Real-world studies should be carried out to evaluate other safety interests. Full article

Background: The term “super responder” identifies a group of patients who exhibit a rapid and optimal response to biological treatment compared to the overall treated population. The primary objective of our study is to characterize this subgroup of patients to enable the early identification of those who will respond most effectively to the proposed treatment while also evaluating clinical efficacy. Methods: This retrospective study evaluated 232 patients treated with guselkumab in monotherapy for at least 20 weeks between November 2018 and November 2023. Patients were divided into two groups: those who achieved complete clear skin (PASI = 0) during the first 20 weeks of treatment were defined as super responders (SRe) and non-super responders (nSRe) were the remaining patients. PASI was assessed at weeks 0, 4, and subsequently every eight weeks. Predictors of the SRe status were evaluated by univariate and multivariate logistic regression analyses. Results: The univariate analyses showed that patients with psoriatic arthritis at the baseline, bio-naïve patients, or those who had not received an interleukin (IL) 17 inhibitor as their last therapy before guselkumab administration were more likely to be super responders to the proposed treatment. Multivariate logistic analysis models suggested that the combination of psoriatic arthritis at the baseline and the bio-naïve condition was the strongest predictive model for the SRe status. At week 204, the main difference between the two groups concerned the achievement of PASI100, maintained by 86.8 of SRe compared to 62.8% of nSRe. Conclusions: The efficacy and safety of guselkumab are confirmed in our real-life experience. Identifying the SRe status will undoubtedly play a role in clinical practice and the therapeutic decision-making algorithm. Full article

Background/Objectives: Several treatment options with differing mechanisms exist for plaque psoriasis. The objective of this analysis was to compare the time to onset of action among the available systemic therapies for plaque psoriasis. Methods: Randomized controlled trials that investigated two or more therapeutics for the management of moderate to severe plaque psoriasis were included. A weighted average time for 50% of patients to reach PASI75 and PAI90 with each of the therapeutics was calculated. A network meta-analysis was performed to determine which therapeutics were significantly faster in time to meaningful clinical response than others. Results: IL-17 inhibitors had the shortest time to achieve PASI75 and PASI90 followed by risankizumab in the weighted mean analysis. In the meta-analysis, the fastest time to PASI75 was seen with bimekizumab, brodalumab and ixekizumab. No significant (p < 0.05) difference was seen in the time to meaningful clinical response between these drugs; however, bimekizumab was significantly faster in time to PASI75 among the remaining therapeutics. In the meta-analysis for PASI90, the fastest time was seen with ixekizumab, bimekizumab, risankizumab, secukinumab and guselkumab with no significant differences in between these therapeutics. However, bimekizumab was significantly faster than the remaining therapeutics for PASI90. Conclusions: IL-17 and IL-23 inhibitors may be considered as requiring the shortest time for meaningful clinical response in plaque psoriasis. In addition to the time to onset, the safety profile of each drug needs to be considered when deciding on a therapeutic to initiate. Full article

Background: The management of pediatric dermatological conditions such as alopecia areata (AA), psoriasis, atopic dermatitis (AD), and hidradenitis suppurativa (HS) has significantly evolved with the introduction of biologics and small molecule targeted therapies. The advancement in understanding the immunopathogenesis of these chronic skin conditions has led to the development and approval of novel biologics and small molecule therapies. Initially approved by the United States Food and Drug Administration (FDA) for adults, most of these therapies are now being evaluated in clinical trials for safety and efficacy in adolescents and children, expanding new treatment options for pediatric patients. The role of the FDA in drug approval is multifaceted from drug inception, ensuring that research, data, and evidence show that the proposed drug is effective and safe for the intended use. Objective: The goal of this review article is to provide an overview of the recently FDA-approved and potential biologic and oral small molecule therapies in clinical trials for AA, psoriasis, AD, and HS in pediatric patients. Methods: The search for this review included keywords in ClinicalTrials.gov, PubMed, and Google Scholar for the latest research and clinical trials relevant to these conditions and treatments without the PRISMA methodology. Results: For pediatric AA, ritlecitinib is FDA-approved, while baricitinib and updacitinib are in phase 3 clinical trials for pediatric approval. The FDA-approved drugs for pediatric psoriasis include secukinumab, ustekinumab, ixekizumab, etanercept, and apremilast. Other phase 3 clinical trials for pediatric psoriasis include risankizumab, guselkumab, tildrakizumab, brodalumab, and deucravacitinib. For pediatric AD, the FDA-approved drugs are dupilumab, tralokinumab, abrocitinib, and upadacitinib, with many other drugs in phase 3 trials. Adalimumab is an FDA-approved biologic for pediatric HS, with various clinical trials ongoing for adults. The approved biologics and small molecule therapies had higher efficacy and improved safety profiles compared to traditional medications. Conclusions: With numerous ongoing trials, the success of these clinical trials could lead to their inclusion in treatment guidelines for these chronic skin conditions. Biologics and small molecule therapies offer new avenues for effective disease management, enabling personalized therapeutic interventions and improving pediatric health outcomes. Full article

Inflammatory cytokines may hold the key to the clinical evolution of psoriasis. The aims of this study are to find a correlation between levels of inflammatory cytokines such as TNF-α, IL-23, IL-17A, and IL-17F and disease duration and severity scores in psoriasis; to test if the decrease in any of the aforementioned cytokines is correlated with an amelioration in disease severity scores; and to analyze if any of the four biologic agents used are linked with a greater decrease in overall cytokine levels. We enrolled 23 adult patients under treatment with ixekizumab, secukinumab, guselkumab, or adalimumab and measured psoriasis disease severity scores PASI (Psoriasis Area Severity Index) and DLQI (Dermatology Life Quality Index), as well as the levels of the aforementioned cytokines at the start of therapy and after 3 months of continuous treatment. Inclusion criteria were the presence of psoriasis, age above 18 years and the need to initiate biological therapy (lack of response to standard treatment). Biological therapies resulted in an amelioration of PASI and DLQI scores, as well as levels of TNF-α, IL-23 and IL-17F. Disease duration and PASI and DLQI scores did not correlate with cytokine levels except DLQI and IL-23 score, in a paradoxically inversely proportional manner. IL-23, in particular, could be a useful biomarker for checking treatment response in psoriasis. Full article

Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of interleukin (IL)-23. Despite its effectiveness and safety, which have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 are limited or characterized by a reduced follow-up period. These data are essential to guide clinicians in biologic switching, considering that anti-IL23 and anti-IL17 partially share their therapeutic targets, as well as some patients who may have to interrupt treatment with anti-IL17 for loss of efficacy over time or the development of adverse events (AEs). In this context, we performed a retrospective study with the aim of evaluating the long-term use (2 years) of guselkumab in psoriasis patients who previously failed at least one anti-IL17 in a real-life setting, also focusing attention on psoriasis located in difficult-to-treat areas (the scalp, palms or soles, fingernails, genitals). A total of 61 patients (35 male, 57.4%; mean age 57.6 ± 8.8 years) were enrolled. Of these, 30 (49.2%) patients failed secukinumab, 21 (34.4%) failed ixekizumab, 7 (11.5%) failed brodalumab, and 3 (4.9%) failed both secukinumab and ixekizumab. At the baseline, the mean PASI and BSA were 12.8 ± 8.4 and 24.5 ± 26.6, respectively. During week 16, PASI90 and PASI100 responses were achieved by 60.7% and 37.7% of patients, respectively, which continued to improve up to week 104 (PASI90: 73.8%, PASI100: 59.0%). Clinical improvement in difficult-to-treat areas was detected as well. In particular, a slower improvement for fingernails and the palmoplantar region was reported compared to scalp and genital psoriasis at week 16. However, no differences were found following 28 weeks of therapy. Primary and secondary inefficacy were reported by 1 (1.6%) and 5 (8.2%) patients. As regards safety, no severe AEs were collected. Full article