Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Tildrakizumab is a humanized, IgG1/κ antibody that interacts with the p19 subunit of interleukin 23. It is approved for the treatment of moderate-to-severe plaque psoriasis. Real-world evidence on the effectiveness and safety of tildrakizumab is limited. OBJECTIVES: To assess the effectiveness and safety of tildrakizumab at 24 weeks in patients with moderate-to-severe plaque psoriasis in routine clinical practice. METHODS: Retrospective, observational, multicentre study including adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab under real-life conditions. Patient data were extracted from anonymized electronic medical records. Statistical analysis was performed using SPSS22. RESULTS: A total of 190 patients were included. About 53.9% were men with a mean age of 51.45 (SD 3.9) and a mean BMI of 29.13 (SD 6.21). About 79.8% (132 out of 190) of patients had previously received biological therapy (BT) and 17.3% (33 out of 191) had psoriatic arthritis. Baseline PASI was 10.7 (SD 6.53). Up to 109 patients reached Week 24 and at this point mean baseline PASI decreased to 1.7 (SD 4.8), representing an 88.79% mean PASI reduction. At 6 months, 87.1% and 40.3% of the treated patients achieved PASI ≤3 and ≤1, respectively. At Week 24 mean BSA decreased from 13.2 (SD 10.07) to 1.6 (SD 4.40) and mean DLQI went from 12.5 (SD 7.12) to 1.2 (SD 3.27). Multivariate analysis showed no differences when effectiveness was correlated with gender, obesity, psoriatic arthritis or prior exposure to BT. The rate of adverse events (AE) was 5.9% (11 out of 190), where infections were the most frequent AE (4 out of 11). One patient suffered a haemorrhagic ictus and one patient died due to causes unrelated to the study. CONCLUSION: Tildrakizumab was effective and safe in a large cohort of patients with moderate-to-severe plaque psoriasis treated in a routine clinical setting.

Bimekizumab in the Treatment of Plaque Psoriasis: Focus on Patient Selection and Perspectives.

Psoriasis is a chronic systemic inflammatory disease that significatively impairs patients' quality of life. Biological treatments are highly effective and safe and have led to breakthroughs in the management of patients with moderate-to-severe psoriasis. However, therapeutic response can be unsatisfactory or lost with time, leading to discontinuation of treatment. Bimekizumab is a humanized monoclonal antibody that specifically inhibits both interleukin (IL)-17A and IL-17F. The efficacy and safety of bimekizumab in moderate-to-severe plaque psoriasis has been demonstrated in Phase 2 and Phase 3 clinical trials. Bimekizumab may offer some advantages over other biological treatments, making it especially indicated for certain patients. This narrative review aims to summarize the latest published evidence on the use of bimekizumab for the treatment of moderate-severe plaque psoriasis, focusing on patient selection and therapeutic perspectives. Bimekizumab has been shown to be more efficacious than adalimumab, secukinumab and ustekinumab in clinical trials, with high estimated probabilities of achieving complete (approximately 60%) or almost complete clearance (approximately 85%) of psoriasis at weeks 10-16, and a good safety profile. Response to bimekizumab is usually fast and maintained in the long term for both biologic-naive patients and those resistant to previous biologic treatments. The usual maintenance dose of 320 mg every 8 weeks makes bimekizumab especially convenient for non-compliant patients. Moreover, the efficacy and safety of bimekizumab have also been demonstrated in psoriasis affecting challenging-to-treat areas, psoriatic arthritis and hidradenitis suppurativa. In conclusion, dual inhibition of IL-17A and IL-17F with bimekizumab is a good therapeutic option for moderate-to-severe psoriasis.

Artritis psoriásica / Psoriatic arthritis

Psoriatic arthritis (PsA) is a type of inflammatory arthritis that is included within the spondyloarthritis, a group of rheumatological diseases characterized by different clinical manifestations and associated comorbidities, that can compromise the quality of life of patients. The diagnosis of PsA is sometimes difficult due to an enormous clinical and radiological variability, including six different domains of involvement: peripheral joint, axial skeleton, skin psoriasis, nail psoriasis, enthesitis and dactylitis. Currently, there are no biomarkers that allow the detection of PsA in patients with psoriasis, so a high level of suspicion is important, mainly by dermatologists, but also by other specialists, such as family doctors. Advances in the knowledge of new immunological mechanisms and joint management by rheumatologists and dermatologists have made it possible to improve the therapeutic approach in patients with PsA. (AU)

La artritis psoriásica (APs) es un tipo de artritis inflamatoria que se incluye dentro de las espondiloartritis, un grupo de enfermedades reumatológicas caracterizadas por diferentes manifestaciones clínicas y comorbilidades asociadas, que pueden comprometer significativamente la calidad de vida de los pacientes. Su enorme variabilidad clínica y radiológica dificulta la sospecha diagnóstica y justifica su abordaje según seis dominios de afectación: articular periférica, esqueleto axial, psoriasis cutánea, psoriasis ungueal, entesitis y dactilitis. En la actualidad no existen biomarcadores que permitan la detección de APs en pacientes con psoriasis, por lo que es importante un alto nivel de sospecha, fundamentalmente por los dermatólogos, pero también por otros especialistas, como son los médicos de familia. El avance en el conocimiento de nuevos mecanismos inmunológicos y el manejo conjunto por parte de reumatólogos y dermatólogos ha permitido mejorar el abordaje terapéutico en los pacientes con APs. (AU)

Psoriatic arthritis. / Artritis psoriásica.

Psoriatic arthritis (PsA) is a type of inflammatory arthritis that is included within the spondyloarthritis, a group of rheumatological diseases characterized by different clinical manifestations and associated comorbidities, that can compromise the quality of life of patients. The diagnosis of PsA is sometimes difficult due to an enormous clinical and radiological variability, including six different domains of involvement: peripheral joint, axial skeleton, skin psoriasis, nail psoriasis, enthesitis and dactylitis. Currently, there are no biomarkers that allow the detection of PsA in patients with psoriasis, so a high level of suspicion is important, mainly by dermatologists, but also by other specialists, such as family doctors. Advances in the knowledge of new immunological mechanisms and joint management by rheumatologists and dermatologists have made it possible to improve the therapeutic approach in patients with PsA.

A cohort study of guselkumab in the treatment of psoriasis refractory to previous biologic therapies: effectiveness, safety and adherence.

Background Guselkumab is indicated for moderate-to-severe plaque psoriasis. Data from real-life clinical practice regarding its use are scarce, especially concerning patients who relapse after previous biologic therapies. Aim This study aimed to evaluate the effectiveness, safety, and adherence to guselkumab in psoriasis refractory to biologic therapies. Method This real-life, retrospective study included patients who initiated guselkumab between February 2019 and October 2020. The main objective was to assess effectiveness, expressed as the psoriasis area and severity index (PASI) ≤5, ≤2 and 0, at the first follow-up medical visit. As secondary effectiveness outcomes, we assessed the body surface area (BSA) and dermatology life quality index (DLQI). We also evaluated adverse events and adherence (using the medication possession ratio [MPR]). Results The study included 35 patients who had previously received a median of two biologic drugs. The median basal PASI score (IQR) was 11 (7.3-15.9), decreasing to 0 (0-1.4) at first follow-up medical visit. At this point, 32 patients (94.1%) reached PASI ≤5, 28 (82.4%) PASI ≤2 and 19 (55.9%) PASI 0. We also found statistically significant improvements in PASI, BSA and DLQI at first follow-up (p<0.001). Three patients developed adverse events. Most patients (N=29, 85.3%) had an MPR ≥90%. The MPR was not associated with PASI score at first follow-up. Conclusion Our study supports evidence that guselkumab is an effective and safe drug in psoriasis refractory to biologic therapies. Adherence to treatment is not related to effectiveness, suggesting that, in some cases, the interval between doses could be increased.

Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (-9.3; [-10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value.

Effectiveness and safety of ustekinumab 90 mg in patients weighing 100 kg or less: a retrospective, observational, multicenter study.

Background: Scant information from clinical practice is available on the effectiveness and safety of ustekinumab (UST) 90 mg in patients with psoriasis weighing 100 kg or less.Objectives: To assess the effectiveness and safety at weeks 16 and 24 of UST 90 mg in patients with psoriasis weighing ≤100 kg, and to study the impact on clinical outcomes of body mass index (BMI) and prior exposure to UST 45 mg.Methods: A retrospective, observational, and multicenter study of 74 adult patients who were treated with UST 90 mg at least 24 weeks.Results: Mean (standard deviation [SD]) score on psoriasis area and severity index (PASI) was 7.9 (4.8) at baseline, 3.3 (3.5) at week 16, and 2.2 (2.4) at week 24, when 69.7% of the patients had a PASI under 3. Overweight and obese patients achieved a mean PASI of 2.2 by week 24 (p= .995). In patients who had previously been treated with UST 45 mg (52/74) with insufficient response, mean (SD) absolute PASI score was 2.7 (2.6) at week 24. No serious adverse events were reported.Conclusions: In patients who weigh 100 kg or less but are overweight or obese and do not present an adequate response with UST 45 mg, increasing the dose to UST 90 mg could be an alternative option.

Biosimilars for the treatment of psoriasis.

Introduction: Biosimilars are biological products that are very similar to their originators, with no meaningful differences in terms of efficacy, safety, and purity. Since the patents of some of the biologics used to treat patients with psoriasis have expired, uptake of biosimilars provides a good opportunity to reduce the cost of treatment. Areas covered: In this review we summarize the stages in development of a biosimilar product, the main differences with the originator biologic, and their potential implications. We have also reviewed clinical trials of biosimilars approved for the treatment of psoriasis. Expert opinion: Because of efficacy and convenience of administration, adalimumab biosimilars will be used to greater extent than etanercept or infliximab to treat patients with moderate-to-severe psoriasis. The pharmacokinetics, efficacy, safety and immunogenicity of approved biosimilars are equivalent to those of their reference products in clinical trials, and multiple-switch studies are intended to provide evidence in support of FDA-required interchangeability. Non-medical switching is expected to become frequent, and the nocebo effect will be relevant. Traceability of biologics is an essential requirement to gather relevant information on their long-term efficacy and safety, especially when multiple switches occur.

Treatment of patients with plaque psoriasis with secukinumab in a real-life setting: a 52-week, multicenter, retrospective study in Spain.

Background: The efficacy and safety of secukinumab in patients with plaque psoriasis (PsO) have been demonstrated in randomized clinical trials (RCTs). However, data regarding its efficacy and safety in real-life settings are scarce. Objectives: To evaluate the efficacy and safety of secukinumab in clinical practice in patients with PsO attending 10 dermatology centers in Spain. Methods: Data from 136 patients consecutively treated with secukinumab for at least 52 weeks were collected in a retrospective observational study. Results: After 52 weeks of treatment, 69% and 46% of patients achieved a PASI-75, PASI-90, respectively. PASI-score ≤5 was achieved in 83% of patients, PASI-score ≤3 in 73% and PASI-score ≤1 in 47%. Response rates were found significantly lower in patients with obesity and non-naïve to biologics (p < .05). The most common adverse event (AE) was candidiasis (5/136). Thirty-six patients (26.5%) discontinued treatment by week 52 due to lack or loss of response (n = 29), AEs (n = 2) or other causes (n = 5). Conclusion: These findings complement the efficacy and safety profiles of secukinumab in PsO outlined in RCTs. The effectiveness in clinical practice may be lower in patients with a BMI ≥30 and those previously treated with other biologic agents.

Secukinumab is the most efficient treatment for achieving clear skin in psoriatic patients: a cost-consequence study from the Spanish National Health Service.

OBJECTIVE: To compare the cost consequence of biologic drugs for moderate-to-severe psoriasis from the perspective of the Spanish National Health System. METHODS: We built a decision tree with a two-year time horizon. Efficacy data for biologics (etanercept, infliximab, adalimumab, ustekinumab and secukinumab) were drawn from published meta-analyses: PASI75 for the induction phase and PASI90 for the rest of follow-up. Patients with PASI < 75 at week 10-16 were switched to another biologic agent. Efficacy at week 24 was considered the highest possible efficacy for each drug and assumed to remain constant throughout the two-year period. Only drug treatment costs were used. The number needed to treat (NNT), annual cost per patient, annual cost per patient with PASI90 (cost per responder) and cost of primary failure (PASI < 75 at first efficacy evaluation) were calculated. RESULTS: Secukinumab monotherapy was associated with the lowest cost per responder, followed by infliximab and ustekinumab. Treatment sequences starting with secukinumab were the most efficient, having the lowest NNT and cost per responder. Although the annual cost per treatment is similar for all drugs, there are huge differences in the cost per responder. CONCLUSIONS: Secukinumab as first-line biologic treatment is the most efficient treatment for moderate-to-severe plaque psoriasis in the short-to-medium term.

The AGEs of Psoriasis: A Biomarker for Severity and a Pathogenetic Link to Comorbidities.

is missing (In this Issue).

ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis): A retrospective observational study on biologic drug survival in daily practice.

BACKGROUND: Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Previous studies have yielded inconsistent results. OBJECTIVES: We sought to analyze long-term biologic survival and its associated variables in a large, real-life cohort of patients with moderate to severe chronic plaque psoriasis. METHODS: This was an observational retrospective study. Data were extracted from clinical records of 427 patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression. RESULTS: We analyzed 703 treatment courses. Overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months, 95% confidence interval 17.4-28.6) than in patients with body mass index less than 30 (37.3 months, 95% confidence interval 29.4-45.1, P = .001), and it was significantly higher for ustekinumab than for any other biologic agent (log rank test P < .001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment, and PASI75 and PASI90 responses at week 16 prolonged drug survival. LIMITATIONS: Data were collected retrospectively. CONCLUSIONS: These findings can facilitate the daily treatment of psoriatic patients and promote long-term effectiveness of biologic therapies.

Secukinumab (AIN457) for the treatment of psoriasis.

Psoriasis is a chronic inflammatory disease with a multifactorial origin that appears in patients with genetic predisposition and is induced by environmental factors, and characterized by alterations in the innate and adaptive immunity. IL-17A is one of the specific cytokines involved in the pathogenesis of psoriasis and its inhibition is highly effective in the treatment of patients with moderate and severe psoriasis. Secukinumab is a monoclonal antibody that specifically binds to IL-17A and inhibits the interaction to its receptor, and it has demonstrated its efficacy and safety in the treatment of psoriasis. Phase II and III clinical trials indicate that > 80% of the patients receiving secukinumab achieve Psoriasis Area Severity Index (PASI) 75 at week 12. In the Phase III efficacy of response and safety of two fixed secukinumab regimens in psoriasis trial, PASI 75 rates were 81.6% with 300 mg secukinumab, 71.6% with 150 mg secukinumab and 4.5% with placebo, and responses were maintained up to 52 weeks in the majority of patients. In the Phase III Full Year Investigative Examination Of Secukinumab versus Etanercept Using Two Dosing Regimens To Determine Efficacy in Psoriasis study, the efficacy of secukinumab was compared to etanercept. The results indicate that both doses of secukinumab (150 and 300 mg) showed superior efficacy compared with etanercept throughout the study; PASI 75 rates at week 12 were 77.1% with 300 mg secukinumab, 67% with 150 mg of secukinumab, 44% with etanercept and 4.9% with placebo. PASI 90 and PASI 100 were 54 and 24% with secukinumab 300 mg and 21 and 4% with etanercept at week 12. At week 52, PASI 90 continued to be higher in the secukinumab group (65%) compared with the etanercept group (33%). Regarding safety, the most common side effects were nasopharyngitis and headache. The rate of infections was higher with secukinumab than placebo. This was especially the case for Candida infections, which were more common in the secukinumab group (4.7% with secukinumab 300 mg and 2.3% with secukinumab 150 mg), but all cases were resolved with conventional treatment. Secukinumab is a well-tolerated treatment that has demonstrated efficacy in treating moderate-to-severe plaque psoriasis. Nevertheless, long-term studies are necessary to confirm Phase II and Phase III data.

Ustekinumab treatment of TNF antagonist-induced paradoxical psoriasis flare in a patient with psoriatic arthritis: case report and review.

BACKGROUND: Therapy with tumour necrosis factor α (TNF) inhibitors can be associated with paradoxical reactions, namely the de novo development or flaring of conditions that usually respond to these therapeutic agents, such as arthritis, inflammatory bowel disease, sarcoidosis or psoriasis. They are considered a class effect of these drugs, and their incidence ranges from 1 to 5%, with paradoxical psoriasis (psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis and their combinations) being most frequently reported. Treatment of paradoxical psoriasis often requires withdrawal of the inducing drug and switching to another anti-TNF agent, but often this cannot avoid recurrence or persistence of the rash and/or loss of the therapeutic effect on the underlying condition. CASE REPORT: We report on a 47-year-old woman who developed incapacitating palmoplantar pustulosis and psoriasis vulgaris flare with severe scalp and nail involvement after 5 months of treatment with adalimumab for psoriatic arthritis. Several treatments, including topical corticosteroids, photochemotherapy, ciclosporin, acitretin and etanercept 50 mg twice a day for 1 month, were ineffective or not tolerated. Treatment with ustekinumab 45 mg provided complete resolution of skin lesions with acceptable therapeutic control of the arthritis, with a follow-up duration of 16 months. CONCLUSION: A review of the reported cases suggests that this may be a therapeutic option in patients who develop paradoxical psoriasis while under treatment for arthritis or Crohn's disease.

Changes in the invasive and metastatic capacities of HT-29/M3 cells induced by the expression of fucosyltransferase 1.

Lewis antigens are terminal fucosylated oligosaccharides synthesized by the sequential action of several glycosyltransferases. The fucosyltransferases are the enzymes responsible for the addition of terminal fucose to precursor oligosaccharides attached to proteins or lipids. These oligosaccharides, defined as cell surface markers, have been implicated in different types of intercellular interactions and in adhesion and invasion processes. Transfection of HT-29/M3 colon cancer cells with the full length of human fucosyltransferase (FUT1), induces the synthesis of H type 2 and Lewis y antigens, associated with a decrease of sialyl-Lewis x. The capacity to develop primary tumors when cells were injected intrasplenically was similar in parental and FUT1-transfected cells, but the capacity to colonize the liver after spleen removal was significantly reduced in M3/FUT1 transfected cells. These results indicate that the expression of FUT1 induces changes in the metastatic capacity of HT-29/M3 colon cancer cells, as a consequence of the altered expression pattern of type 2 Lewis antigens. Also, an association between MUC5AC expression and the degree of gland differentiation in both primary splenic tumors and hepatic metastases was detected.

Role of sialyltransferases involved in the biosynthesis of Lewis antigens in human pancreatic tumour cells.

The sialylated carbohydrate antigens, sialyl-Lewisx and sialyl-Lewisa, are expressed in pancreatic tumour cells and are related to their metastatic potential. While the action of the fucosyltransferases involved in the synthesis of these antigens has already been investigated, no studies have been carried out on the activity and expression of the alpha 2,3-sialyltransferases in pancreatic tumour cells. We describe the sialyltransferase (ST) activity, mRNA expression, and analysis of the cell carbohydrate structures in four human pancreatic adenocarcinoma cell lines of a wide range of neoplastic differentiation stages and in normal human pancreatic tissues. Total ST activity measured on asialofetuin, employing a CMP fluorescent sialic acid, varied among the pancreatic cell lines and could be correlated to the expression of their cell surface antigens. However, in some of the pancreatic cell lines, no relationship could be established with their ST3Gal III and IV mRNA expression. Human pancreatic tissues also showed ST expression and activity. However, it presented a much higher expression of neutral fucosylated structures than sialylated structures. In conclusion, ST activity levels in pancreatic cells could be correlated to their expression of sialylated epitopes, which indicates their involvement in the formation of the sialyl-Lewis antigens, in addition to fucosyltransferase activities.