Certolizumab pegol effectiveness, survival and safety in patients with psoriasis: A multicenter retrospective analysis in daily clinical practice by the Spanish Psoriasis Group.

BACKGROUND: Certolizumab is an Fc-free PEGylated tumor necrosis factor-alpha (TNFα) inhibitor recently approved for the treatment of moderate-to-severe plaque psoriasis, although there is limited real-world evidence on the effectiveness and safety in patients with plaque psoriasis treated with certolizumab. The objective of this article is to determine the effectiveness, drug survival, and safety, including pregnancy, childbirth, and lactation, of certolizumab in moderate-to-severe plaque psoriasis under real-world conditions. METHODS: This is a retrospective, multicenter, observational study performed in 15 hospitals in Spain. It evaluates the effectiveness and safety of certolizumab in plaque psoriasis in the clinical practice setting. RESULTS: A total of 67 patients (73% female) were evaluated with a mean baseline Psoriasis Area Severity Index (PASI) of 8.9. At Week 12, the mean PASI was 2.3 (n = 67), 1.3 (n = 57) at Week 24 and 1.3 at Week 52 (n = 34). Absolute PASI < 3 was achieved in 69, 86, and 92% of patients at Weeks 12, 24, and 52, respectively, as observed. For its part, using the under-response imputation analysis, PASI < 3 at Weeks 12, 24, and 52 were achieved by 69, 73, and 49% of the patients, respectively. A total of 35 patients (52%) had concomitant psoriatic arthritis, and, in 24 of them, Disease Activity in Psoriatic Arthritis Score (DAPSA) was recorded at baseline, with a mean value of 17.9 which decreased to 8.2 at Week 12 (n = 22) and to 3.6 at Week 24 (n = 18). Certolizumab treatment was discontinued in 14 out of 67 patients (21%), due to lack/loss of cutaneous or articular effectiveness (n = 11) or patient decision (n = 2) or adverse event in only one patient who developed active tuberculosis. A lower baseline PASI [hazard ratio (HR): 1.12 (1.02-1.23); P = 0.023] and a more significant reduction in PASI at Week 12 [HR: 1.16 (1.07-1.27); P < 0.001] and Week 52 [HR: 1.47 (1.11-1.96); P = 0.007] was shown to be significantly related with better survival for the entire follow-up period. Fourteen patients were treated during pregnancy and/or lactation without reporting adverse events in either the patient or the newborn. CONCLUSIONS: Certolizumab consistently showed high effectiveness and drug survival rates in this real-life cohort. The safety demonstrated in clinical trials during pregnancy and lactation seems to be confirmed in clinical practice.

Fast and sustained improvement of patient-reported outcomes in psoriatic patients treated with secukinumab in a daily practice setting.

Psoriasis is a chronic dermatological disease with great impact on patients' quality of life (QoL). The main objective of this study was to assess the impact of secukinumab treatment on different patient-reported outcomes (PROs) during a long-term follow-up in Spanish patients with moderate-to-severe psoriasis under real-world conditions. Retrospective, observational, open-label, nationwide multicenter cohort study that included patients who initiated treatment with secukinumab in daily clinical practice conditions. PROs assessing disease impact and QoL included Dermatology Life Quality Index (DLQI), Patient's Global Psoriasis Assessment, Itch Numerical Rating Scale and EuroQoL Thermometer Visual Analogue Scale. Outcomes, including PROs and Psoriasis Area and Severity Index (PASI), were assessed at months 3, 6, 12, 18, and 24 during treatment. A total of 238 patients were enrolled in the study. Patients had a mean DLQI score of 14.9 at baseline; 78.3%, 73.7%, and 71.7% of them achieved a DLQI 0/1 response at months 6, 12, and 24, respectively. DLQI score was lower in the long term for naïve patients. A sharp decrease in mean DLQI was observed during the first 3 months, reaching a plateau that was maintained until the end of follow-up. Similar findings were observed for the rest of QoL assessments. There was a close association between improvement in QoL and skin clearance (PASI), which progressively increased during follow-up. In this study, secukinumab sustainably improved patient's QoL during a 24-month follow-up, with strongest effects in patients naïve to biological therapies and with a direct correlation with PASI improvement.

The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry.

BACKGROUND: Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES: To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS: All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS: Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = .0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS: Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.

Autochthonous and imported tegumentary leishmaniasis in Catalonia (Spain): Aetiological evolution in the last four decades and usefulness of different typing approaches based on biochemical, molecular and proteomic markers.

Leishmaniasis is a transmissible disease caused by Leishmania protozoa. Spain is endemic for both visceral and cutaneous leishmaniasis, the autochthonous aetiological agent being Leishmania infantum. Around the world, the L. donovani complex is associated with visceral symptoms, while any species of the Leishmania or Viannia subgenera affecting human can produce tegumentary forms. In a context of growing numbers of imported cases, associated with globalisation, the aim of this study was to analyse the aetiological evolution of human tegumentary leishmaniasis in a region of Spain (Catalonia). Fifty-six Leishmania strains, isolated from 1981 to 2018, were analysed using MLEE, gene sequencing (hsp70, rpoIILS, fh and ITS2) and MALDI-TOF. The utility of these different analytical methods was compared. The results showed an increase in leishmaniasis over the two last decades, particularly imported cases, which represented 39% of all cases studied. Leishmania infantum, L. major, L. tropica, L. braziliensis, L. guyanensis and L. panamensis were identified. The combination of molecular and enzymatic methods allowed the identification of 29 different strain types (A to AC). Strain diversity was higher in L. (Viannia), whilst the different L. major types were relatable with geo-temporal data. Among the autochthonous cases, type C prevailed throughout the studied period (39%). Minor types generally appeared within a short time interval. While all the techniques provided identical identification at the species complex level, MALDI-TOF and rpoIILS or fh sequencing would be the most suitable identification tools for clinical practice, and the tandem hsp70-ITS2 could substitute MLEE in the epidemiological field.

Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain.

INTRODUCTION: There is limited and conflicting evidence over the real-world drug survival of secukinumab (SEC) in patients with psoriasis, especially in the long term. Our objective was to analyze the short- and long-term survival of SEC (S-SEC) and its predictive factors for the treatment of psoriasis. METHODS:  Patients clinically diagnosed with plaque psoriasis and under treatment with secukinumab (n = 384) in a daily practice setting were analyzed in a retrospective, multicenter study performed in a nationwide cohort and followed up for a period of 2 years. Kaplan-Meier curve was plotted to analyze drug survival time, and log-rank test was performed to compare several groups. Factors related to speed of treatment discontinuation were studied with a Cox regression model. RESULTS: The overall cumulative secukinumab drug survival rates observed at 6, 12, 18, and 24 months were 97.1%, 89.0%, 81.1%, and 74.3%, respectively. Obesity [hazard ratio (HR), 1.809, CI 95% 1.114-2.962; p = 0.004] and previous experience with biological therapies, particularly those who had been treated with ≥ 2 biologicals with different mechanisms of action (HR 3.476, CI 95% 1.875-6.444; p = 0.017) were associated with an early discontinuation, whereas psoriatic arthritis was associated with delayed discontinuation, (HR 0.493, CI 95% 0.265-0.917; p = 0.025). CONCLUSIONS: In our study, we found that cumulative secukinumab drug survival for psoriasis patients for the period 6-18 months was in the range of real-world evidence studies. Additionally, we observed a relatively high long-term survival rate at 24 months (74.3%).

Effect of Sex in Systemic Psoriasis Therapy: Differences in Prescription, Effectiveness and Safety in the BIOBADADERM Prospective Cohort.

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be prescribed biologics. There were no differences between men and women in effectiveness of therapy, measured in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Multiparametric analysis of the effectiveness of cisplatin on cutaneous squamous carcinoma cells using two different types of adjuvants.

The objective of this study was to regulate the cytotoxicity of cisplatin (cisPt) minimizing its adverse effects. For this purpose, the lowest cisPt concentration needed to obtain a significant positive response in cutaneous squamous cell carcinoma (cSCC) was explored. Two adjuvant agents as gold nanoparticles (AuNP) and chelating tricine were tested as enhancers in cisPt treatment. Effectiveness of all treatments was assessed by means of biochemical techniques, which offer quantitative data, as well as two microscopy-based techniques that provided qualitative cell imaging. The present work confirms the effectiveness of free cisplatin at very low concentrations. In order to enhance its effectiveness while the side effects were probably diminished, cisPt 3.5 µM was administered with AuNP 2.5 mM, showing an effectiveness practically equal to that observed with free cisPt. However, the second treatment investigated, based on cisPt 3.5 µM combined with tricine 50 mM, enhanced drug effectiveness, increasing the percentage of cells dying by apoptosis. This treatment was even better in terms of cell damage than free cisPt at 15 µM. Images obtained by TEM and cryo-SXT confirmed these results, since a notable number of apoptotic bodies were detected when cisPt was combined with tricine. Thus, tricine was clearly a better adjuvant for cisPt treatments.

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.

Relevancia del tratamiento de portadores rectales asintomáticos de Mycoplasma genitalium en hombres que tienen sexo con hombres / Importance of the treatment of rectal Mycoplasma genitalium in men who have sex with men

No disponible

Sexually transmitted infections in young people and factors associated with HIV coinfection: an observational study in a large city.

OBJECTIVES: Young people are a critical target group for sexually transmitted infections (STI) surveillance due to their particular behavioural and social related vulnerability. The aim of this study was to describe the epidemiological characteristics and trends in the incidence of gonorrhoea, syphilis, HIV and venereal lymphogranuloma (LGV) among 15-24-year-olds in Barcelona, and to determine factors associated with HIV coinfection. DESIGN: We performed a population-based incidence study covering the 2007-2015 period. PARTICIPANTS: All new cases of STI-HIV, gonorrhoea, infectious syphilis and LGV-notified to the epidemiological surveillance system in Barcelona between 2007 and 2015. 1218 cases were studied: 84.6% were men, 19.3% were 15-19 years old and 50.6% were born in Spain. Among men, 73.7% were men who have sex with men (MSM); among women, 85.6% were women that have sex with men. PRIMARY AND SECONDARY OUTCOMES: Incidence of HIV, gonorrhoea, infectious syphilis and LGV. HIV coinfection. RESULTS: There was an increase in the incidence of gonorrhoea, from 1.9 cases per 10 000 people in 2007 to 7.6/10 000 in 2015 (p<0.01), in MSM from 27.1 to 228.8/10 000 (p<0.01). The incidence of syphilis increased from 0.4/10 000 in 2007 to 3.1/10 000 in 2015 (significant in men only, p<0.01), in MSM from 18.1 to 116.9/10 000 (p<0.01). The incidence of HIV showed a non-significant increase in men (p=0.27), and that of LGV remained stable (p=0.59). Factors associated with increased risk of HIV coinfection included being MSM (adjusted OR[ORa]=14.14, 95% CI 3.34 to 59.91) and having >10 sexual partners (ORa=4.11, 95% CI 1.53 to 11.01) or STI diagnosis during the previous 12 months (ORa=2.06; 95% CI 1.13 to 3.77). CONCLUSIONS: The incidence of gonorrhoea and syphilis among 15-24-year-olds increased, while HIV infection remained stable but with a high incidence among MSM. Being MSM, having sex with multiple partners and having a diagnosis of an STI in the previous 12 months were factors associated with HIV coinfection.

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.

Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content.

OBJECTIVES: Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent in vitro study showed that tissue-derived mast cells can capture and release exogenous IL-17A. The present study aimed to investigate if this mechanism could contribute to tissue inflammation in SpA. METHODS: Potential activation of mast cells by IL-17A was assessed by gene expression analysis of the Laboratory of Allergic Diseases 2 (LAD2) mast cell line. The presence of IL-17A-positive mast cells was assessed by immunohistochemistry in synovial tissue obtained before and after secukinumab treatment, as well as in skin and gut tissues from SpA-related conditions. RESULTS: IL-17A did not induce a pro-inflammatory response in human LAD2 mast cells according to the canonical IL-17A signalling pathway. In SpA synovial tissue, the percentage of IL-17A-positive mast cells increased upon treatment with secukinumab. IL-17A-positive mast cells were also readily detectable in non-inflamed barrier tissues such as skin and gut. In non-inflamed dermis and gut submucosa, IL-17A-positive mast cells are the most prevalent IL-17A-positive cells in situ. Compared with non-inflamed tissues, both total mast cells and IL-17A-positive mast cells were increased in psoriatic skin dermis and in submucosa from inflammatory bowel disease gut. In contrast, the proportion of IL-17A-positive mast cells was strikingly lower in the inflamed compared with non-inflamed gut lamina propria. CONCLUSION: IL-17A-positive mast cells are present across SpA target tissues and correlate inversely with inflammation, indicating that their IL-17A content can be regulated. Tissue-resident mast cells may act as IL-17A-loaded sentinel cells, which release IL-17A to amplify tissue inflammation.

Gay Circuit Parties in Barcelona and Their Impact on Gonorrhea Incidence.

This study explored the role of circuit parties on the incidence of gonorrhea among men who have sex with men (MSM) in Barcelona (Spain). Specifically, it aimed to detect cyclic peaks in the number of reported diagnoses of gonorrhea after gay circuit parties. We analyzed monthly cases of gonorrhea reported from January 2007 through December 2016 after the main annual gay circuit parties in Barcelona. We used the integer autoregressive model for time series with discrete values. The performance of the model was tested in heterosexual men and women, in whom the circuit parties could be expected to have no impact. A sensitivity analysis was conducted, changing post-event diagnosis windows to 1 week later/1 week before. In the study period, a total of 4182 of gonorrhea cases were detected, of which 74.8% (n = 2181) occurred in men who identified themselves as MSM. The average annual increase in gonorrhea cases reported among MSM was 32.57%. In an independent analysis of each gay circuit party, cases increased significantly in two of them. The results were also similar for same-sex practices among men only. On controlling for the increasing trend over the study period and the seasonal effect, an average of 1.16 gonorrhea cases in MSM (95% CI: 0.68, 1.64) were attributable to the celebration of one of the gay circuit parties considered. During the expected outbreak, an average of 13 gonorrhea cases were detected and between 5 and 13% were attributable to one of the circuit parties. In view of these findings, participants should consider seeking advice from their healthcare provider and practice safer sex using condoms to prevent sexually transmitted infections. Local public health services should be reinforced to ensure care for participants during and after gay circuit parties. More research is needed to design and implement preventive programs.