S.P. Menting

Composition of Innate Lymphoid Cell Subsets in the Human Skin: Enrichment of NCR+ ILC3 in Lesional Skin and Blood of Psoriasis Patients

Innate lymphoid cells (ILCs) are increasingly appreciated as important regulators of tissue homeostasis and inflammation. However, their role in human skin remains obscure. We found that healthy peripheral blood CD117(+) ILC3, lacking the natural cytotoxicity receptor (NCR) NKp44 (NCR(-) ILC3), CD117(-)NCR(-)CRTH2(-)CD161(+) ILC1, and CRTH2(+) ILC2, express the skin-homing receptor cutaneous lymphocyte antigen (CLA). NCR(+) ILC3 were scarce in peripheral blood. Consistently, we identified in normal skin ILC2 and NCR(-) ILC3, a small proportion of CD161(+) ILC1, and hardly any NCR(+) ILC3, whereas NCR(+) ILC3 were present in cultured dermal explants. The skin ILC2 and NCR(+) ILC3 subsets produced IL-13 and IL-22, respectively, upon cytokine stimulation. Remarkably, dermal NCR(-) ILC3 converted to NCR(+) ILC3 upon culture in IL-1β plus IL-23, cytokines known to be involved in psoriatic inflammation. In line with this observation, significantly increased proportions of NCR(+) ILC3 were present in lesional skin and peripheral blood of psoriasis patients as compared with skin and blood of healthy individuals, respectively, whereas the proportions of ILC2 and CD161(+) ILC1 remained unchanged. NCR(+) ILC3 from skin and blood of psoriasis patients produced IL-22, which is regarded as a key driver of epidermal thickening, suggesting that NCR(+) ILC3 may participate in psoriasis pathology.

Drug survival is not significantly different between biologics in patients with psoriasis vulgaris: a single‐centre database analysis

Drug survival depends on several factors such as dosing, effectiveness, quality‐of‐life improvement and safety, and could be seen as an overall marker for treatment success. Such data for biologics in psoriasis treatment are sparse.

Developing a Therapeutic Range of Adalimumab Serum Concentrations in Management of Psoriasis: A Step Toward Personalized Treatment

IMPORTANCE Adalimumab has proven to be effective in suppressing psoriasis disease activity and is administered in a standard dose. OBJECTIVE To establish a therapeutic range for adalimumab trough levels in the treatment of plaque-type psoriasis, leading to a more personalized treatment. DESIGN, SETTING, AND PARTICIPANTS A multicenter, prospective, observational, daily practice cohort study conducted at an academic hospital with affiliated secondary care hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2). Both cohorts included adult patients treated with adalimumab for plaque-type psoriasis. Cohort 1 comprised 73 patients who were being treated with adalimumab for more than 24 weeks until 401 weeks. In cohort 2 (n = 62), serum samples were obtained between weeks 24 and 52 of treatment. INTERVENTIONS Before the start of adalimumab therapy and at time of serum sampling, Psoriasis Area and Severity Index (PASI) scores were determined. MAIN OUTCOMES AND MEASURES Adalimumab trough level and PASI score at the time of serum sampling to determine the receiver-operator characteristics analyses and concentration effect curve. RESULTS By means of receiver-operator characteristics analyses with an area under the curve of 0.756 (SD, 0.046; 95% CI, 0.666-0.847) and a sensitivity of 78% and a specificity of 70%, 3.51 mg/L was established as the lower margin for the therapeutic range. By means of a concentration effect curve, 7 mg/L was established as the upper margin. One-third of patients had an adalimumab trough concentration exceeding 7 mg/L. CONCLUSIONS AND RELEVANCE A therapeutic range of adalimumab trough levels of 3.51 mg/L to 7.00 mg/L, which corresponds to an optimal clinical effect, was identified. In one-third of patients, it was observed that trough concentrations exceeded the therapeutic window. Based on the established range, a therapeutic algorithm for adalimumab treatment for patients with psoriasis can be developed and validated in a prospective patient cohort. By identifying this range, a step has been taken toward a more rational use of biological therapy in psoriasis. Developing a therapeutic algorithm may lead to less overtreatment of patients and cost savings.

An increased risk of non-melanoma skin cancer during TNF-inhibitor treatment in psoriasis patients compared to rheumatoid arthritis patients probably relates to disease-related factors

Concerns exist about a risk of non‐melanoma skin cancer (NMSC) in psoriasis patients and rheumatoid arthritis (RA) patients treated with TNF‐inhibitors. However, current data also show that in some psoriasis patients, NMSC is diagnosed relatively short after the start of TNF‐inhibitors, which suggests that these NMSC can be explained by previous therapies instead of by TNF‐inhibitor therapy.

The correlation of clinical efficacy, serum trough levels and antidrug antibodies in ustekinumab‐treated patients with psoriasis in a clinical‐practice setting

Several therapeutic antibodies are available for the treatment of chronic plaque type psoriasis. Ustekinumab (a monoclonal IL12/23 antagonist) is one of these antibodies (1) and it is currently being investigated for other indications. For adalimumab (a monoclonal tumour necrosis factor α antagonist) a positive correlation has been observed between adalimumab trough levels and clinical efficacy, both showing a negative correlation with anti-drug antibodies (ADA) to adalimumab (present in 49% of patients) (2). In rheumatoid arthritis, a therapeutic range for adalimumab trough level has been established, which can eventually lead to a more personalised way of administering adalimumab (3). This article is protected by copyright. All rights reserved

Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial

BackgroundThe introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases.MethodsThis is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past.DiscussionOPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy.Trial registrationNTR4499. Registered on 7 April 2014.

Procollagen-3 N-terminal peptide measurements for the detection of liver fibrosis in methotrexate-treated patients with psoriasis: Daily practice use and clinical implications

In the past, a varying incidence of liver fibrosis, which was attributed to methotrexate (MTX) treatment for psoriasis, has been reported.(1-5) However, recent reports show lower incidences of liver fibrosis in this group, and a low or absent risk attributable to MTX.(6,7) Dawwas et al. found that end-stage liver disease related to MTX was very uncommon (0.07% of 158 904 liver transplant patients), and that features of the metabolic syndrome were prevalent in those affected.(6) This article is protected by copyright. All rights reserved