There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the University Medical Center Utrecht and Groningen, the Netherlands, were analysed. NMSC after oral immunosuppressive treatment was reported in 18 patients (3.2%). The standardized incidence ratio for developing SCC was 13.1 (95% confidence interval (95% CI) 6.5-19.7). Patients developing NMSC were older at the start of therapy (p<0.001) and data lock (p<0.001) compared with patients without NMSC. No significant differences were found in sex, cumulative days of oral immunosuppressive drugs and follow-up between these groups (p=0.42, p=0.88, and p=0.34, respectively). In interpreting these results it is important to include other factors, such as lack of association between treatment duration and tumour development and the long interval between treatment discontinuation and tumour development in some patients.

Data regarding the efficacy and safety of methotrexate (MTX) in adults with localized scleroderma (LoS) is scarce. This study gathered data from a retrospective cohort of adult patients with LoS (n?=?107), treated with MTX (1993-2015). MTX drug survival and predictors thereof were analysed. After 1 and 2 years, 26% and 63% of patients stopped MTX due to disease remission, respectively. Patients with younger age at MTX initiation (hazard ratio (HR) 1.159 (95% confidence interval (CI) 1.052-1.277)) and those with no other autoimmune diseases (HR 3.268 (95% CI 1.334-8.009)) more often stopped MTX due to disease remission. In addition, 24% of patients stopped MTX due to treatment failure within one year. Patients with circumscribed superficial LoS (HR 0.221 (95% CI 0.081-0.601)) experienced treatment failure less often than those with other LoS subtypes. Finally, adding folic acid (HR 0.184 (95% CI 0.079-0.425)) and reducing treatment delay (HR 1.056 (95% CI 1.004-1.112)) could be the most important factors in minimizing MTX treatment failure in LoS in clinical practice.

Background:Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine.Methods:To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment.Results:A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02–3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6–positive and HLA-Cw6–negative patients (P = 0.164).Conclusions:The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.

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 registration NTR4499. Registered on 7 April 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1777-y) contains supplementary material, which is available to authorized users.