Publications

OBJECTIVE: Anti-tumor necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.

METHODS: Prospective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.

RESULTS: Of 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.

CONCLUSION: This analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.

BACKGROUND: Short-term interleukin-23p19 inhibition by tildrakizumab improves plaque psoriasis and appears to be well tolerated.

OBJECTIVES: Safety and tolerability were assessed for up to 64 weeks of tildrakizumab therapy using pooled data from three randomized controlled trials for moderate-to-severe psoriasis.

METHODS: Data pools for the placebo-controlled (up to 16 weeks) and full trial periods (up to 64 weeks) were analysed (n = 2081).

RESULTS: In the placebo-controlled period, frequencies of treatment-emergent adverse events (TEAEs; range 47·9-54·0%), serious TEAEs (range 1·4-2·3%), discontinuations due to AEs (range 0·6-1·9%), major adverse cardiovascular events (MACEs; range 0·0-0·1%) and severe infections (range 0·0-0·3%) were comparable between tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept. In the full trial period, exposure-adjusted rates (patients per 100 patient-years) for TEAEs, serious TEAEs and discontinuations due to AEs with tildrakizumab 100 mg and 200 mg were lower than or comparable with the placebo rates, and lower than with etanercept. Exposure-adjusted rates of MACEs (range 0·0-0·5) and severe infections (range 0·9-2·0) were comparable among groups. No TEAEs of inflammatory bowel disease or suicide were reported. Candida skin infections were infrequent at frequencies of 0·1%, 0·3%, 0·0% and 0·0% for the tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept groups, respectively, in the placebo-controlled period, and exposure-adjusted rates of 0·2, 0·7, 0·0 and 0·0, respectively, in the full trial period. Oral candidiasis was also infrequent.

CONCLUSIONS: Up to 64 weeks of tildrakizumab was well tolerated, with low rates of serious TEAEs, discontinuations due to AEs, and AEs of clinical interest.

Hidradenitis suppurativa (HS) is a frequently devastating inflammatory skin disorder. Although many treatments have been tried and tested to date, there is only one Food and Drug Administration-approved treatment option, adalimumab, which is currently indicated for moderateto- severe HS. Our understanding of the management of HS with biologic agents and with nonantibiotic and/ or antimicrobial systemic therapies continues to evolve. In this article, we summarize the existing data on biologics and other small-molecule systemic agents, as well as share our personal experiences with the pharmacological management of HS in the clinical setting. Continued challenges that limit our ability to study and treat this disease effectively include a lack of a universally employed scoring system for disease severity, high variability in clinical presentation, high cost of off-label therapy, and the scarcity of long-term studies on treatment response and medication safety.

Hidradenitis Suppurativa Clinical Response (HiSCR), is a validated tool that has been used to assess the efficacy of adalimumab among patients with hidradenitis suppurativa. We evaluated the clinical meaning of HiSCR by relating it to patient-reported outcomes to give further context to its achievement in a post hoc analysis of integrated data from two phase 3 clinical trials (PIONEER I and II). Pooling placebo and active treatment arms, 39% of patients (245/629) achieved HiSCR at week 12. Irrespective of treatment, significantly (p <0.05) more HiSCR responders than non-responders experienced clinically meaningful improvement in Dermatology Life Quality Index (60.5% vs 30.4%), Pain Numeric Rating Scale (46.9% vs 19.9%), hidradenitis suppurativa quality of life (49.4% vs 26.9%), work-related performance (52.6% vs 37.7%), and non-work-related performance (59.5% vs 33.3%). Clinically meaningful outcomes in hidradenitis suppurativa are more likely to be attained in patients achieving HiSCR level improvement.

BACKGROUND: Hidradenitis suppurativa clinical response (HiSCR) is a validated clinical end point for measuring response to treatment in patients with hidradenitis suppurativa (HS). Previous studies have reported on the validity, responsiveness and meaningfulness of the HiSCR.

OBJECTIVE: To evaluate the HiSCR for inter- and intrarater reliability characteristics.

METHODS: A stand-alone, two-site, prospective, non-interventional observational study consisted of 22 patients, with self-reported severity between mild, moderate and severe HS. The Patient Global Impression of Change (PGI-C) scale was completed by patients at Timepoint 2. Descriptive statistics of Hurley Stage, total abscesses, total draining fistulas, total inflammatory nodules and total AN count (sum of inflammatory nodules and lesions) were reported at two timepoints. Inter-rater reliability and intrarater reliability for the HS lesion count tool were evaluated at two timepoints (baseline and Day 7) using the HS lesion count tool. Intraclass correlation (ICC) coefficients of lesion counts were calculated to evaluate inter- and intrarater reliability of lesion counts between pairs of dermatologists.

RESULTS: The majority of patients demonstrated either no change or minimally worse PGI-C in HS scores. Descriptive statistics were similar between rater groups and timepoints assessed. Inter-rater ICC coefficients for abscess count at Timepoints 1 and 2 were 0.38 and 0.67. The ICC coefficients for draining fistula and AN count were ≥0.61 at both timepoints. In an exploratory model, ICC coefficients were ≥0.68 for all evaluated lesion counts. The test-retest reliability using ICC coefficients was ≥0.70 for total abscess, draining fistula, inflammatory nodule and AN count.

CONCLUSION: The HS lesion count tool had an acceptable inter- and intrarater reliability, indicating that HiSCR has a strong degree of reproducibility and consistency in the evaluation of patients with HS.

INTRODUCTION: Prior studies have reported that hidradenitis suppurativa (HS) is accompanied by a myriad of physical and mental conditions. However, given the small sample sizes and the limited number of pre-selected comorbidities, these studies do not provide a complete picture of the comorbidity burden of HS in the USA. Moreover, the relationship between HS severity and comorbidity burden has yet to be characterized. Using a large US claims database, we estimated the comorbidity burden associated with HS, stratified by disease severity.

METHODS: A retrospective matched cohort design was used. Patients with HS were classified into two severity cohorts (milder and more severe) using an empirical algorithm based on treatments received. The comorbidity burden was compared between each HS cohort and their matched HS-free cohort, and between patients with milder vs. those with more severe forms of HS.

RESULTS: Several physical and mental comorbidities were found to be more prevalent in both cohorts of patients with milder and more severe forms of HS than in their matched HS-free cohorts. The comorbidity burden also increased greatly as the disease progressed to more severe forms.

CONCLUSIONS: The results of this study highlight the complexity of the comorbidity burden of HS patients and the need for a multidisciplinary approach to optimize the management of HS and its numerous associated comorbidities.

FUNDING: AbbVie, Inc.