Keywords: adalimumab; fibrosis; fistulous tracts; hidradenitis suppurativa; power-Doppler; ultrasound Fistulous tracts are the hallmark lesions of hidradenitis suppurativa (HS) and respond poorly to ...the currently available medical treatments. To evaluate the clinical and ultrasound features related with both healing and persistence of fistulous tracts in patients under treatment with adalimumab, a retrospective analysis of power-Doppler ultrasound (PD-US) images with fistulas in HS patients was performed. The clinical and sonographic staging of HS, body areas involved, and anatomic characteristics of the fistulous tracts were registered and graded. Chi-square test, univariate/multivariate Cox-regression analysis with clustered error, and Kaplan-Meier analysis were computed to analyze data. In total, 151 fistulous tracts from 33 HS patients were included. Age, BMI, length, thickness, subcutaneous pattern, high intensity of PD-US signal, and a high grade of fibrosis/edema were all related to a lower possibility of healing and a high risk of longer persistence at binomial Cox-regressions. Whereas, multivariate regressions showed that high fibrosis, was the variable with the highest risk of poor response and longer survival. Survival-analysis showed that fistulas with high fibrosis or PD-US signal have longer survival time than those with absent/low fibrosis or signal. Limitations include the impossibility to detect with ultrasound lesions less than 0.1 mm and smaller sample size. In conclusion, an accurate assessment of fibrosis may be crucial to define better when a surgical approach-besides the medical treatment-could be required. PD-US may assess the decrease of vascularization in HS lesions and consequently the reduction of inflammation due to immunomodulatory therapies. Byline: Raffaele Dante Caposiena Caro, Francesco Maria Solivetti, Eleonora Candi, Luca Bianchi
La dermatosis pustular subcórnea es una dermatosis infrecuente y poco conocida. El objetivo de este trabajo es describir la experiencia de los autores en el diagnóstico y tratamiento de un grupo de ...pacientes colombianos con esta enfermedad. Se presentan seis casos diagnosticados entre los años 2010 y 2021. Todos los afectados tenÃan lesiones de larga evolución (en promedio 5 años) y las zonas del cuerpo más afectadas fueron el tórax (83 %), las axilas (66 %) y el tercio proximal de las extremidades (50 %). Las lesiones semiológicas más comunes fueron las pústulas (83 %), las pápulas (83 %) y las placas eritematocostrosas con bordes circinados (50 %); las pústulas flácidas tÃpicas solo se observaron en dos casos (33 %). En conclusión, el diagnóstico de la dermatosis pustular subcórnea reguiere del reconocimiento de un amplio espectro de manifestaciones clÃnicas, asà como una adecuada correlación clÃnico-patológica. Subcorneal pustular dermatosis is a rare and little known dermatosis. The objective of this paper is to describe the experience of the authors in the diagnosis and treatment of a group of Colombian patients with this disease. Six cases are presented, diagnosed between 2010 and 2021. All of the patients had long-standing lesions (on average 5 years) and the most affected areas were the thorax (83%), the armpits (66%), and the proximal third of the extremities (50%). The most common lesions were pustules (83%), papules (83%), and erythematous-crusted plagues with circinated edges (50%); typical flaccid pustules were only observed in two cases (33%). In conclusion, the timely diagnosis of subcorneal pustular dermatosis reguires recognition of a wide spectrum of clinical presentations, as well as adeguate clinicopathological correlation.
Objective:To evaluate the efficacy of adalimumab in the healing of draining fistulas in patients with active Crohn’s disease (CD).Design:A phase III, multicentre, randomised, double-blind, placebo ...controlled study with an open-label extension was conducted in 92 sites.Patients:A subgroup of adults with moderate to severely active CD (CD activity index 220–450) for ⩾4 months who had draining fistulas at baseline.Interventions:All patients received initial open-label adalimumab induction therapy (80 mg/40 mg at weeks 0/2). At week 4, all patients were randomly assigned to receive double-blind placebo or adalimumab 40 mg every other week or weekly to week 56 (irrespective of fistula status). Patients completing week 56 of therapy were then eligible to enroll in an open-label extension.Main Outcome Measures:Complete fistula healing/closure (assessed at every visit) was defined as no drainage, either spontaneous or with gentle compression.Results:Of 854 patients enrolled, 117 had draining fistulas at both screening and baseline (70 randomly assigned to adalimumab and 47 to placebo). The mean number of draining fistulas per day was significantly decreased in adalimumab-treated patients compared with placebo-treated patients during the double-blind treatment period. Of all patients with healed fistulas at week 56 (both adalimumab and placebo groups), 90% (28/31) maintained healing following 1 year of open-label adalimumab therapy (observed analysis).Conclusions:In patients with active CD, adalimumab therapy was more effective than placebo for inducing fistula healing. Complete fistula healing was sustained for up to 2 years by most patients in an open-label extension trial.ClinicalTrials.gov Identifier: NCT00077779 and NCT00195715.
To determine predictors of treatment success after dose escalation of adalimumab, including measurement of anti-adalimumab antibodies as a predictor of success
Retrospective clinical cohort study
...Single-center academic institution
Patients with noninfectious uveitis who were inadequately controlled or developed recurrent disease on biweekly adalimumab and required dose escalation or therapy modification
Patients who had anti-adalimumab antibodies checked with resultant low to intermediate levels were compared to patients who had no testing performed prior to adalimumab dose escalation. Of note, patients with testing and resultant high levels of anti-adalimumab antibodies were not escalated. Predictors of escalation success and utility of antibody testing prior to escalation were analyzed using Kaplan Meier survival analysis and Cox proportional hazard models.
Treatment success defined as anterior chamber grade ≤0.5+ cell, topical corticosteroids ≤1 drop/day, oral prednisone ≤5 mg/day, resolution of macular edema, and resolution of angiographic signs of inflammation without any addition or escalation of therapy.
24 patients had antibodies tested with low to intermediate levels (average: 32.3 ng/mL, range: 0 – 154), while 41 did not have antibody testing. A greater treatment success rate post escalation was observed among the “low antibody” group compared to the “no testing” group (HR: 2.63, standard error: 1.19, p=0.031, 95% CI 1.09 – 6.37). Among the entire cohort, patients with panuveitis (n = 14) had a lower treatment success rate compared to the reference of anterior uveitis (n = 26) (HR: 0.09, standard error: 0.11, p = 0.05, 95% CI 0.01 – 0.99).
Patients with low anti-adalimumab antibodies had a greater treatment success compared to patients in whom antibodies were not checked. This suggests a utility to checking antibodies prior to dose escalation and that low levels of antibodies may confer a success advantage. Overall, patients with panuveitis had a lower rate of success after escalation while patients with anterior uveitis patients had a very high rate of success suggesting that certain disease characteristics may guide clinicians when determining who to escalate versus changing therapy.
Dose-optimization strategies for biologic therapies in Crohn’s disease (CD) are not well established. The SERENE CD (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in ...Patients With Moderate to Severe Crohn’s Disease) trial evaluated higher vs standard adalimumab induction dosing and clinically adjusted (CA) vs therapeutic drug monitoring (TDM) maintenance strategies in patients with moderately to severely active CD.
In this phase 3, randomized, double-blind, multicenter trial, eligible adults (Crohn’s Disease Activity Index score of 220–450, endoscopic evidence of mucosal inflammation, and previous failure of standard therapies) were randomized to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3; n = 308) or standard induction regimen (adalimumab 160 mg at week 0 and 80 mg at week 2; n = 206) followed by 40 mg every other week from week 4 onward. Co-primary end points included clinical remission at week 4 and endoscopic response at week 12. At week 12, patients were re-randomized to maintenance therapy optimized by Crohn’s Disease Activity Index and C-reactive protein (CA; n = 92) or serum adalimumab concentrations and/or clinical criteria (TDM; n = 92); exploratory end points were evaluated at week 56.
Similar proportions of patients receiving higher induction regimen and standard induction regimen achieved clinical remission at week 4 (44% in both; P = .939) and endoscopic response at week 12 (43% vs 39%, respectively, P = .462). Week 56 efficacy was similar between CA and TDM. Safety profiles were comparable between dosing regimens.
Higher induction regimen was not superior to standard induction regimen, and CA and TDM maintenance strategies were similarly efficacious. Adalimumab therapy was well tolerated, and no new safety concerns were identified. (ClinicalTrials.gov, Number: NCT02065570).
The SERENE CD study results demonstrate no additional benefit of higher adalimumab induction dosing vs the approved standard induction dosing for treating patients with moderately to severely active Crohn’s disease.
Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line ...biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response.
This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080.
Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98–1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator.
Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis.
Novartis Pharma.
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