Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. METHODS: The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. RESULTS: At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. CONCLUSION: Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors.

OBJECTIVES: Hepatitis B reactivation (HBVr) constitutes a side effect of the treatment of autoimmune rheumatic diseases. Even though HBVr risk of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) and anti-tumor necrosis factor (anti-TNF) agents has long been established, the risk of targeted synthetic (ts)DMARDs and anti-interleukin (anti-IL) agents remains largely unknown. METHODS: We conducted a SLR (PubMed, Scopus and EMBASE) and metanalysis to examine the HBVr risk for the following: anti-IL17, anti-IL12/23, anti-IL23 and JAK-inhibitors in patients with chronic HBV infection (HBsAg presence or detectable HBV-DNA) and in patients with prior HBV infection (HBcAb-positive and HBsAg-negative). Meta-analysis was performed using both the fixed and random effects method and was conducted using the R computing language. RESULTS: Overall, our study revealed a low HBVr risk of < 6% in all agents; the risk was significantly higher for people having chronic compared with those with resolved HBV (14,4% vs 5.1%, respectively p< 0.01). There was no difference among different drugs in the HBVr rates [anti-IL-17: 4% (95% CI: 1-9%), anti-IL-12/IL-23: 2% (95% CI: 0-5%), JAK-inhibitors: 4% (95% CI: 1-8%), anti-IL23: 0%]. Of note, HBVr rate reached 28% in patients with chronic HBV who did not receive anti-viral treatment. For patients with resolved hepatitis the respective percentage was 4.7%. CONCLUSION: Overall, our meta-analysis shows that patients with chronic HBV receiving anti-IL-17, anti-IL-12/23, anti-IL-23 and JAK-inhibitors have significant risk for HBVr, especially if they are not under anti-viral treatment. In contrast, resolved HBV seems to offer minor risk for HBVr even without anti-viral treatment.

Effectiveness and Durability of COVID-19 Vaccination in 9447 Patients With IBD: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: The serological responses after severe acute respiratory syndrome coronavirus 2 vaccination may be attenuated in immunocompromised individuals. The study aimed to systematically evaluate the seroconversion rates after complete vaccination for coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD). METHODS: Electronic databases were searched to identify studies reporting response to COVID-19 vaccination in IBD. Pooled seroconversion rates after complete vaccination were calculated. Subgroup analysis for vaccine types was also performed. Pooled seroconversion rates for various drugs or classes were also estimated. The pooled rates of breakthrough infections in vaccinated IBD patients were estimated. The pooled neutralization rates after complete vaccination were also estimated. The studies reporting durability of titers were systematically assessed. RESULTS: A total of 46 studies were included. The pooled seroconversion rate for complete vaccination (31 studies, 9447 patients) was 0.96 (95% confidence interval [CI], 0.94-0.97; I2 = 90%). When compared with healthy control subjects, the pooled relative risk of seroconversion was lower (0.98; 95% CI, 0.98-0.99; I2 = 39%). The pooled seroconversion rates were statistically similar among various drug classes. The pooled positivity of neutralization assays (8 studies, 771 participants) was 0.80 (95% CI, 0.70-0.87; I2 = 82%). The pooled relative risk of breakthrough infections in vaccinated IBD patients was similar to vaccinated control subjects (0.60; 95% CI, 0.25-1.42; I2 = 79%). Most studies suggested that titers fall after 4 weeks of COVID-19 vaccination, and the decay was higher in patients on anti-tumor necrosis factor alone or combination with immunomodulators. An additional dose of COVID-19 vaccine elicited serological response in most nonresponders to complete vaccination. CONCLUSIONS: Complete COVID-19 vaccination is associated with seroconversion in most patients with IBD. The decay in titers over time necessitates consideration of additional doses in these patients.

Emerging drugs for the treatment of inflammatory bowel disease.

INTRODUCTION: Anti-tumor necrosis factor (TNF)-α have been the mainstay therapy for Crohn's (CD) and ulcerative colitis (UC) for decades. With growing need for highly effective therapy, various therapeutic targets have been introduced including anti-integrins, anti-interleukin (IL) 12/23, selective anti-IL23, Janus Kinase (JAK) inhibitors, sphingosine-1-phosphate (S1P) receptor modulators, and mRNA-124 splicing agent. AREAS COVERED: The current state of available IBD therapies and those in development are reviewed, with recommendations made on positioning in clinical practice. EXPERT OPINION: Selecting and sequencing IBD therapies remains a clinical challenge. Disease phenotype, severity of symptoms, patient comorbidities, and prior drug exposure should be considered when considering therapy options. Anti-TNF remains a time-tested option that is effective in both UC and CD. The perception that newer biologics have slower onset of action is probably overestimated and providers should reconsider need for concurrent corticosteroid. JAK-inhibitors provide rapid symptom improvement in patients with moderate-severe UC. Due to safety concerns, it is recommended as a second-line therapy for UC. The goal for IBD treatment should be personalized, have rapid onset of action, induce durable clinical and endoscopic remission, and have excellent safety.

No Benefit of Concomitant Immunomodulator Therapy on Efficacy of Biologics That Are Not Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases: A Meta-analysis.

BACKGROUND & AIMS: There is debate over whether patients with inflammatory bowel diseases (IBD) treated with biologics that are not tumor necrosis factor antagonists (such as vedolizumab or ustekinumab) should receive concomitant treatment with immunomodulators. We conducted a meta-analysis to compare the efficacy and safety of concomitant immunomodulator therapy vs vedolizumab or ustekinumab monotherapy. METHODS: In a systematic search of publications, through July 31, 2019, we identified 33 studies (6 randomized controlled trials and 27 cohort studies) of patients with IBD treated with vedolizumab or ustekinumab. The primary outcome was clinical benefit, including clinical remission, clinical response, or physician global assessment in patients who did vs did not receive combination therapy with an immunomodulator. Secondary outcomes were endoscopic improvement and safety. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs. RESULTS: Overall, combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68-1.05; I2=13.9%; Q test P = .17) or ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87-1.38; I2 = 11%; Q test P = .28). Results were consistent in subgroup analyses, with no difference in clinical remission or response in induction vs maintenance studies or in patients with Crohn's disease vs ulcerative colitis in studies of vedolizumab. Combination therapy was not associated with better endoscopic outcomes in patients receiving vedolizumab (3 studies: OR, 1.13; 95% CI, 0.48-2.68; I2 = 0; Q test P=.96) or ustekinumab (2 studies: OR, 0.58; 95% CI, 0.21-1.16; I2 = 47%; Q test P = .17). Combination therapy was not associated with an increase in adverse events during vedolizumab therapy (4 studies: OR, 1.17; 95% CI, 0.75-1.84; I2 = 0; Q test P = .110). CONCLUSIONS: In a meta-analysis of data from studies of patients with IBD, we found that combining vedolizumab or ustekinumab with an immunomodulator is no more effective than monotherapy in induction or maintenance of remission.

Psoriasis and Atherosclerosis-Skin, Joints, and Cardiovascular Story of Two Plaques in Relation to the Treatment with Biologics.

It is known that both psoriasis (PSO) limited to the skin and psoriatic arthritis (PSA) increase the risk of cardiovascular complications and atherosclerosis progression by inducing systemic inflammatory response. In recent decades, the introduction of biological medications directed initially against TNF-α and, later, different targets in the inflammatory cascade brought a significant breakthrough in the efficacy of PSO/PSA treatment. In this review, we present and discuss the most recent findings related to the interplay between the genetics and immunology mechanisms involved in PSO and PSA, atherosclerosis and the development of cardiac dysfunction, as well as the current PSO/PSA treatment in view of cardiovascular safety and prognosis.

The Course of Mycosis Fungoides under Cytokine Pathway Blockers: A Multicentre Analysis of Real-life Clinical Data.

Literature regarding the effect of biologics on the course of mycosis fungoides (MF) is scarce. This multicentre study analysed retrospective data on 19 patients with MF, who were treated with biologics; 12 for inflammatory conditions coexisting with MF, and 7 for MF misdiagnosed as an inflammatory skin disease. Eight patients were treated with anti-tumour necrosis factor-α-monotherapy; 6 had early-stage MF, in 3 patients MF preceded and in 3 MF was diagnosed after initiation of biologics, with no stage-progression or with stable disease, respectively (median treatment time concurrent with MF 57 months). Two patients had advanced stage MF: IIB, treated for 15 months with no stage-progression, and IVA1, treated for 8 months, died of disease 10 months later. The other 11/19 patients received anti-interleukin-17A and/or anti-interleukin-12/23 or anti-interleukin-23 (with/without anti-tumour necrosis factor-α/anti-interleukin-4/13), with stage-progression in 8 patients after a median of 8 months' treatment. Although, in general, biologics should be avoided in patients with MF, these results indicate that anti-tumour necrosis factor-α-monotherapy might not aggravate the disease course in early-stage patients. Interleukin-17A, interleukin-12/23 and interleukin-23 pathway-blockers may prompt progression of MF.

Pharmacogenetics Update on Biologic Therapy in Psoriasis.

Background and objectives: Psoriasis is a chronic immune-mediated skin disease caused by several complex factors, both environmental and genetic, many of which are still not fully understood. Nowadays, several groups of biological drugs are being used for psoriasis treatment. Although these therapies are very effective, they show significant variability in efficacy among individuals. Therefore, there is a need for biomarkers to predict treatment outcomes in order to guide personalized therapeutic decisions. Pharmacogenetics is the study of variations in DNA sequences related to drug response. Materials and Methods: In this article, we review pharmacogenetics studies on the treatment of moderate-to-severe psoriasis focusing on anti-interleukin (IL) 12/23 (ustekinumab) and anti-IL17 drugs (secukinumab and ixekizumab), as well as recent studies concerning anti-TNF drugs. Results: Several polymorphisms have been studied over the years in reference to anti-TNF drugs; some of the most recent studies included the performance of a genome-wide association study (GWAS) and pharmacogenetics studies focused on the optimization of a treatment regimen. Various polymorphisms in different genes have been related to ustekinumab response; among them, the most commonly studied is the HLA-C*06:02 allele. Conclusions: Although not confirmed in some studies, most studies have shown that patients carrying this allele present a significantly higher response rate to ustekinumab. Some polymorphisms have been studied in patients treated with anti-IL17 drugs, mostly related to secukinumab; however, up to now, no association has been found between any of these polymorphisms and response. Nevertheless, further studies involving larger cohorts are needed in order to confirm these results before the implementation of this biomarker in clinical practice.

Pharmacokinetics and Exposure Response Relationships of Ustekinumab in Patients With Crohn's Disease.

BACKGROUND & AIMS: Ustekinumab is a monoclonal antibody that binds with high affinity to the p40 subunit of human interleukin 12 (IL12 and IL23) that has been approved for treatment of patients with moderate to severe Crohn's disease (CD). However, there are few data on its pharmacokinetic properties or the relationship between drug exposure levels and patient response. We collected data from 2 Phase 3 induction studies and 1 maintenance study to determine ustekinumab's pharmacokinetic features, relationship between exposure and response, and optimal serum concentrations for efficacy. METHODS: We collected data on serum concentrations of ustekinumab and efficacy from induction studies of patients with moderate to severe CD given ustekinumab for 8 weeks following a single intravenous dose (either 130 mg or approximately 6 mg/kg). We collected the same data from a maintenance study of patients with a response to ustekinumab in the induction study who then received subcutaneous injections (90 mg) every 8 or 12 weeks for 44 weeks. At week 44 of the maintenance study (52 weeks after treatment began), patients were evaluated for the primary endpoint of clinical remission (defined as a CD activity index score below 150 points), endoscopic markers of efficacy, and serum level of C-reactive protein. Ustekinumab concentration data were categorized into quartiles and relationships between exposure and response were assessed. Optimal concentration cutoff values were evaluated using receiver operating characteristic curve analysis. RESULTS: Serum concentrations of ustekinumab over time were proportional to dose and did not differ significantly between the induction studies. In the maintenance study, ustekinumab concentration reached the steady state by the second maintenance dose; the median trough concentration was approximately threefold higher in patients given ustekinumab at 8-week intervals compared with 12-week intervals. Ustekinumab serum concentrations associated with rates of clinical remission and endoscopic efficacy endpoints, correlated inversely with level of C-reactive protein, and did not associate with use of immunomodulators. Trough concentrations of ustekinumab of 0.8 (or even up to 1.4 µg/mL) or greater were associated with maintenance of clinical remission in a higher proportion of patients than patients with lower trough concentrations. CONCLUSIONS: In an analysis of data from Phase 3 studies of patients with moderate to severe CD, we found serum concentrations of ustekinumab to be proportional to dose and associate with treatment efficacy. Concentrations of ustekinumab did not seem to be affected by cotreatment with immunomodulators. Clinicaltrials.gov no. NCT01369329 (UNITI 1), NCT01369342 (UNITI 2), and NCT01369355 (IM-UNITI).

Maneuvering Clinical Pathways for Crohn's Disease.

PURPOSE OF REVIEW: Crohn's disease management has changed significantly with increasing use of biologics. We review the recent literature on the clinical management of Crohn's disease and new approaches in selecting and optimizing therapy. RECENT FINDINGS: Recent studies have addressed the efficacy of proactive anti-TNFα trough level monitoring, the efficacy of biosimilars, and the efficacy and immunogenicity of newer biologics including anti-integrin therapy and anti-IL12/23 therapy. Optimizing anti-TNFα therapy according to trough concentrations correlates with improved remission rates. Patients can be switched from the reference drug to a biosimilar, or vice versa, without a measurable change in efficacy, safety, or immunogenicity. Immunomodulators are effective in decreasing immunogenicity and boosting anti-TNFα drug level. The anti-integrin and anti-IL12/23 therapies are effective as induction and maintenance therapy with low immunogenicity and excellent safety profiles. Patients at high risk for post-operative recurrence should be started on a biologic therapy within 4 weeks post-op. Multiple biologic therapies are currently available for treatment of Crohn's disease including anti-TNFα therapy, anti-integrin therapy, and anti-IL12/23 therapy. The choice of first-line therapy should be based on individual risk-benefit analysis, route of administration, and patient preference. Patient with inadequate response should have their trough level checked and therapy optimized. Therapeutic prophylaxis for post-operative recurrence should be based on patient's risk factors for recurrence.

[Pityriasis rubra pilaris]. / Pityriasis rubra pilaire.

Pityriasis rubra pilaris is a rare heterogeneous dermatosis associating three clinical signs to different degrees: follicular corneal papules, reddish-orange palmoplantar keratoderma and erythematosquamous lesions that may in some cases be very extensive, interspersed with patches of healthy skin. The aetiology is unclear, and in most cases, the trigger factors consist of trauma or infection, probably in subjects with an existing predisposition. In other cases, the condition is associated with immunological disorders or, in familial cases, genetic keratinisation abnormalities similar to ichthyosis. Given the widely varying signs, several classifications have been proposed, based on clinical criteria and outcomes. The outcome varies in accordance with the clinical forms involved. Therapeutic approaches are poorly qualified and there have been no clinical trials due to the rarity of the disease. However, the best results appear to have been obtained using oral retinoids, with second-line therapy comprising methotrexate and cyclosporine. The landscape of therapeutic strategy seems to be changing with the advent of new anti-tumour necrosis factor and anti-interleukin-12/23 antibodies.

Fetal death in utero and miscarriage in a patient with Crohn's disease under therapy with ustekinumab: case-report and review of the literature.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD). CASE PRESENTATION: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage. CONCLUSION: Ustekinumab is a relatively new pharmacotherapy and in addition to this clinical case, we reviewed the published literature concerning the use of this treatment during pregnancy and its consequences on pregnancy and fetus outcome.

Management of patients with psoriasis treated with biological drugs needing a surgical treatment.

Tumor necrosis factor alpha (TNF-α) is a cytokine that plays a critical role in inflammatory and immune processes and in the control of infections and sepsis. Data on the perioperative management of patients treated with biologic drugs are limited and mainly in patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). This retrospective study assesses variations in the incidence of side effects between psoriatic patients who temporarily discontinue or continue biological therapy before surgical treatment. Despite the immunosuppressive risk, our results suggest that postoperative complications are not influenced by the suspension of biologic therapies. As TNF-α plays a role in promoting collagen synthesis and wound healing, we suggest that anti-TNFs should be discontinued before major surgery, whereas for minor surgery, the lower rates of infections favor anti-TNF-α continuation, particularly since suspending anti-TNF therapy is known to induce psoriasis relapse.

Anti-IL23/12 agents and JAK inhibitors for inflammatory bowel disease.

IBD (inflammatory bowel disease) is a chronic inflammatory disease of the gastrointestinal tract with increasing incidence worldwide. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been implicated in the cause of IBD, although the cause of the disease remains unknown. IL-12 and IL-23 and their downstream signaling pathways participate in the pathogenesis of inflammatory bowel disease. Early and aggressive treatment with biologic therapies or novel small molecules is needed to decrease complications and the need for hospitalization and surgery. The landscape of inflammatory bowel disease (IBD) treatment has tremendously improved with the development of biologics and small molecule drugs. Several novel biologics and small molecule drugs targeting IL-12 and IL-23 and their downstream targets have shown positive efficacy and safety data in clinical trials, and several drugs have been approved for the treatment of IBD. In the future, numerous potential emerging therapeutic options for IBD treatment are believed to come to the fore, achieving disease cure.

Remission of refractory Crohn's disease with anti-IL-12/23 therapy in a patient undergoing hemodialysis: A case report.

Crohn's disease is a relapsing chronic inflammatory condition of the intestine with increasing prevalence around the world. Biologic therapies are currently widely used and have proved safe and effective in treating moderate to severe Crohn's disease. However, contemporary bibliography contains little information about the use of these drugs in patients with end-stage renal disease undergoing hemodialysis. Here we present a case of a 47-year-old female patient with treatment-refractory Crohn's disease on hemodialysis. In this patient, treatment with the anti-IL-12/23 receptor antibody ustekinumab was effective in inducing and maintaining remission while being safe in administering throughout hemodialysis.

Cost per responder of biologic drugs used in the treatment of moderate-to-severe plaque psoriasis in France and Germany.

OBJECTIVE: The treatment of moderate-to-severe plaque psoriasis has seen significant improvements in recent years with the advent of biologic drugs. The aim of this study was to assess the cost-effectiveness of anti-IL17 drugs and other biologic therapies used to treat moderate-to-severe plaque psoriasis in France and Germany over a one-year time horizon. METHODS: We developed a cost per responder model for biologic drugs used in psoriasis treatment. The model included anti-IL17s (brodalumab, secukinumab, ixekizumab and bimekizumab), anti-TNFs (adalimumab, etanercept, certolizumab and infliximab), an anti-IL12/23 (ustekinumab), and anti-IL23s (risankizumab, guselkumab and tildrakizumab). Efficacy estimates were collected through a systematic literature review of network meta-analyses on long-term Psoriasis Area and Severity Index (PASI) measures. Dose recommendations and country-specific prices were used to calculate drug costs. Biosimilar drug prices were used when available as a substitute for the originator drugs. RESULTS: After one year, brodalumab had the lowest cost per PASI100-responder in both France (€20,220) and Germany (€26,807) across all available biologic treatments. Among the anti-IL17s, brodalumab had a 23% lower cost per PASI100-responder vs. the nearest comparator in France (bimekizumab, €26,369), and 30% lower vs. nearest comparator in Germany (ixekizumab, €38,027). Brodalumab also had the lowest cost per PASI75- and PASI90-responder among the anti-IL17s in both France and Germany after one year. Adalimumab had the lowest cost per PASI100-responder among the anti-TNFs in both France (€23,418) and Germany (€38,264). Among the anti-IL-23s, risankizumab had the lowest cost per PASI100-responder in both France (€20,969) and Germany (€26,994). CONCLUSION: Driven by its lower costs and high response rates, brodalumab was the most cost-effective treatment option for moderate-to-severe plaque psoriasis over a one-year time-horizon within the anti-IL17 class and when compared to all other biologics in France and Germany.

Allelic Variants of HLA-C Upstream Region, PSORS1C3, MICA, TNFA and Genes Involved in Epidermal Homeostasis and Barrier Function Influence the Clinical Response to Anti-IL-12/IL-23 Treatment of Patients with Psoriasis.

Several biologic therapies have been developed to treat moderate-to-severe psoriasis, with patients exhibiting different clinical benefits, possibly due to the heterogeneity of pathogenic processes underlying their conditions. Ustekinumab targets the IL-12/IL-23-p40 subunit and inhibits type-1 and type-17 T-cell responses. Although ustekinumab is effective as both short- and long-term treatment, therapeutic response varies considerably among patients. Ustekinumab biosimilars will be commercialized in the very next future, likely broadening the use of this drug in the treatment of psoriasis patients. Our pharmacogenomic study evaluated the influence of 417 single-nucleotide polymorphisms (SNPs) in psoriasis-risk alleles on the clinical response to ustekinumab in a cohort of 152 patients affected by moderate-to-severe plaque-type psoriasis. Differences in SNP pattern characterizing HLA-Cw6+ or HLA-Cw6- patients, showing high or low responses to ustekinumab, were also analysed. We identified twelve SNPs in HLA-C upstream region (rs12189871, rs4406273, rs9348862 and rs9368670), PSORS1C3 (rs1265181), MICA (rs2523497), LCE3A-B intergenic region (rs12030223, rs6701730), CDSN (rs1042127, rs4713436), CCHCR1 (rs2073719) and in TNFA (rs1800610) genes associated with excellent response to ustekinumab. We also found that HLA-Cw6+ and HLA-Cw6- patients carried out distinct patterns of SNPs associated with different clinical responses. The assessment of HLA-C alleles, together with other genetic variants, could be helpful for defining patients who better benefit from anti-IL-12/IL-23 therapy.

Adherence and Persistence to Biological Drugs for Psoriasis: Systematic Review with Meta-Analysis.

Despite the large number of biologics currently available for moderate-to-severe psoriasis, poor adherence and persistence to therapy represent the main issues for both the clinical and economic management of psoriasis. However, the data about adherence and persistence to biologics in psoriasis patients are conflicting. Our aim was to produce summary estimates of adherence and persistence to biologics in adult patients with psoriasis. We performed a systematic review and meta-analysis of observational studies, searching two databases (PubMed and Embase). Sixty-two records met the inclusion criteria, and a meta-analysis was conducted on fifty-five studies. Overall, the proportion of adherent and persistent patients to biological therapy was 0.61 (95% confidence interval: 0.48-0.73) and 0.63 (0.57-0.68), respectively. The highest proportions were found for ustekinumab, while the lowest ones were found for etanercept. The proportions of adherence and persistence to biological drugs in psoriasis patients are sub-optimal. Notably, both proportions largely differ between drugs, suggesting that a more rational use of biologics might ensure better management of psoriasis.

Novel Therapeutic Approaches to Psoriasis and Risk of Infectious Disease.

Psoriasis is a chronic immune-mediated skin and joint disease, with a plethora of comorbidities, characterized by a certain genetic predisposition, and a complex pathogenesis based on the IL-23/IL-17 pathway. There is no doubt that the patients affected by psoriasis are more susceptible to infections as well as that the risk of infection is higher in psoriatic subjects than in the general population. The advent of biotechnological agents on the therapeutic arsenal actually available for the treatment of moderate-to-severe patients, given the fact that the severity of the disease is a predictor of the level of infectious risk, has raised the question of whether these 'new' drugs could be considered a safer option and how they can be used in selected cases. Old and newer strategies in cases of chronic infectious conditions are reviewed under the light of clinical trials and other studies present in literature.

Beyond the Skin Plaques: Psoriasis and Its Cardiovascular Comorbidities.

Psoriasis, a widely prevalent chronic disease of the skin and joints, has long been associated with far-reaching systemic ramifications and decreased quality of life. However, psoriasis is largely underdiagnosed and insufficiently treated. Classical risk factors predisposing to cardiovascular diseases, such as hypertension, diabetes, metabolic syndrome, and dyslipidemia, have been noted in patients with mild and severe psoriasis. Furthermore, the magnitude of the cardiovascular comorbidity and the need to screen for risk factors has often been ignored while considering the management options for psoriasis. This article has reviewed the cardiovascular implications of psoriasis from the shared pathogenesis behind these two diseases to the increased incidence of cardiovascular events, such as myocardial infarction, stroke, and other causes of vascular mortality. Additionally, the therapeutic targets of common inflammatory pathways, such as those involving tumor necrosis factor α (TNF-α), interleukin-12/interleukin-23 (IL-12/IL-23), and helper T cells 17 (Th17), have been discussed with an emphasis on their efficacy in controlling psoriasis and its cardiovascular consequences.