Therapeutic drug monitoring in patients with inflammatory bowel disease on ustekinumab.

OBJECTIVE: Therapeutic drug monitoring is used clinically to guide anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD), but its use for ustekinumab (UST) remains unclear. This study aimed to determine predictive variables of UST levels. METHODS: In this retrospective cohort of patients with IBD, UST trough levels were drawn at maintenance dosing. Relationships between UST trough levels and demographics, therapy, and outcomes were analyzed. Machine-learning models were used to infer combinatorial traits predictive of UST levels. RESULTS: Altogether 177 patients with IBD on UST had a mean UST trough level of 4.742 µg/mL. The injection schedule correlated significantly (P < 0.001) with UST levels. Naiveté to anti-TNFs correlated with higher UST levels (P = 0.048). Univariate analysis revealed that higher inflammatory biomarkers significantly correlated to lower UST levels and a lower Simple Endoscopic Score to Crohn's Disease to adequate UST levels (P = 0.018). Multivariate analysis identified body mass index (BMI), previous anti-TNF failure, and laboratory flare as predictors of UST levels with an area under the receiver operating characteristic curve (AUROC) of 0.72. The UST cut-off level of 5.77 µg/mL yielded a 0.79 AUROC, 80% sensitivity, and 81% specificity for predicting endoscopic remission of Crohn's disease. For the clinical remission end-point in ulcerative colitis, UST level of 4.73 µg/mL yielded a 0.69 AUROC, 53% sensitivity, and 86% specificity. CONCLUSIONS: Higher UST levels correlated with less disease activity. BMI was an important consideration for UST response as well. Therefore, UST dose adjustments to reach target levels may optimize response.

Clinical efficacy, drug sustainability and serum drug levels in Crohn's disease patients treated with ustekinumab - A prospective, multicenter cohort from Hungary.

INTRODUCTION: Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort. METHODS: Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. RESULTS: A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI<150 and C-reactive protein<10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y. CONCLUSION: Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required.

Evaluation of ustekinumab trough levels during induction and maintenance therapy with regard to disease activity status in difficult to treat Crohn disease patients.

ABSTRACT: Ustekinumab (UST) is approved for the treatment of moderate and severe Crohn disease (CD). Therapeutic drug monitoring (TDM) can help monitor the therapeutic effects of biologics. Therefore, the aim of this study was to evaluate the clinical outcomes of UST-treated CD patients and to determine the UST trough level in clinical and corticosteroid-free remission.This retrospective study included patients with moderate and severe active disease (AD) treated intravenously with a weight-adapted induction dose of UST. The maintenance therapy consisted of 90 mg UST subcutaneously at week 8 and thereafter every 8 or 12 weeks, depending on the clinical response. Clinical and corticosteroid-free remission, Harvey-Bradshaw-Index (HBI), UST trough level, and further laboratory parameters were measured just before the injection of UST at each follow-up evaluation until week 40.37 CD patients with a median HBI of 9 at week 0 were included in the study. Starting from 24% at the beginning of the monitoring period, and 38% of patients at the end of the monitoring period were treated with an 8-week interval (P = .18). There was a significant improvement in clinical (P = .0004), corticosteroid-free remission (P = .03), and HBI (P < .0001) from week 0 until the end of the observation period. The serum UST trough level decreased significantly from 2.0 at week 8 to 0.3, in the maintenance therapy and 0.4 µg/ml at the end of the therapy (P < .0001). Neither UST trough level nor levels of C-reactive protein (CRP) or fecal calprotectin (FC) were associated with disease outcome. Concomitant immunomodulator therapy did not appear to affect the UST trough level or clinical course.UST is an effective treatment option for difficult-to-treat patients with CD. UST trough levels may not be associated with treatment efficacy or the prediction of treatment outcomes in patients with CD. Further prospective randomized trials should be conducted to evaluate whether UST trough levels are associated with treatment outcomes in patients with CD.

Endoscopic Activity and Serum TNF-α Level at Baseline Are Associated With Clinical Response to Ustekinumab in Crohn's Disease Patients.

BACKGROUND AND AIMS: The therapeutic efficacy and safety of ustekinumab for Crohn's disease (CD) have been reported from randomized controlled trials and real-world data. However, there are few studies describing the identification of patients most suitable for ustekinumab therapy. The aim of this study was to prospectively evaluate the patients receiving ustekinumab and identify predictors of the treatment efficacy. METHODS: Patients with moderate to severe active CD scheduled to receive ustekinumab were enrolled. The responders and nonresponders were compared at weeks 0, 8, 24, and 48 by evaluating patient demographics, simple endoscopic scores (SES-CD), ustekinumab and cytokine concentrations, and cellular fractions. RESULTS: The clinical response and clinical remission rates in the 22 enrolled patients were 59.1% and 31. 8% at week 8, 68.2% and 45.5% at week 24, and 54.4% and 40.9% at week 48, respectively. There were no significant differences in patients' demographic and disease characteristics at baseline between responders and nonresponders. A combination of low SES-CD and high serum TNF-α concentration at baseline showed a good correlation with the clinical response. Serum TNF-α concentration was decreased because of the therapy. The ratio of CD4+TNF-α cells at baseline was significantly higher in responders than in nonresponders; however, the ratios of CD45+CD11b+TNF-α and CD45+CD11c+TNF-α cells were not different. The ratio of CD4+ TNF-α cells decreased with the treatment in the responders but not in the nonresponders. CONCLUSIONS: The combination of 2 factors, namely higher serum TNF-α concentration and lower SES-CD at baseline, may assist clinicians in selecting the appropriate therapy for patients with moderate to severe CD.

Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study.

Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2-4.2) and in 10.6% (95% CI = 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 µg/ml [95% CI = -1.190 to -0.30] and -0.74 µg/ml [95% CI = -1.09 to -0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0-9.9] and 1.9 [95% CI = 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn's disease - a regional multi-center pilot study.

BACKGROUND AND AIM: The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn's disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16. METHODS: Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration. RESULTS: Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001). CONCLUSION: Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation.

Development of a Mass Spectrometry-Based Method for Quantification of Ustekinumab in Serum Specimens.

BACKGROUND: Ustekinumab (UST) is a human monoclonal antibody used to treat moderate-to-severe Crohn disease by blocking the interleukin-12/23 pathway. Although an optimized therapeutic concentration of UST is associated with clinical response and improved prognosis, the availability of clinical laboratory methods for UST monitoring is limited. Furthermore, the commercially available methods are immunoassays that are prone to interference of antidrug antibodies. This study aimed to develop a liquid chromatography-tandem mass spectrometry method for quantification of UST in human serum specimens. METHODS: A tryptic peptide that is specific to the heavy chain variable region of UST was selected. Quantification of UST was performed by selective reaction monitoring on a quadrupole TQ-XS with an internal standard. After digestion with trypsin, peptides were separated by reverse-phase C18 liquid chromatography; peptides were detected by MS/MS, and analyte to internal standard peak area ratios were used for the quantification. Finally, serum samples from patients treated with UST were collected at trough levels (n = 66). RESULTS: The assay showed a broad dynamic range with linearity between 0.4 and 20 mg/L (R = 0.995). The lower limit of quantification was found to be 0.4 mg/L. The reproducibility was tested with 3 different UST concentrations (2, 8, and 16 mg/L). The coefficients of intra-assay and interassay variations were 2.2%-4.0% and 2.7%-5.3%, respectively. UST serum concentrations of 2-16 mg/L were stable for up to 14 days when specimens were left at room temperature (20°C). CONCLUSIONS: The newly developed LC/MS-based method was shown to be feasible for UST quantification. This analytical approach may lead to individualized dosing and improved patient care.

Ustekinumab Serum Trough Levels May Identify Suboptimal Responders to Ustekinumab in Crohn's Disease.

INTRODUCTION: The aim of this study was to evaluate the association between serum ustekinumab (UST) trough levels and response to induction and maintenance UST treatment in refractory Crohn's Disease (CD) patients. METHODS: We performed a prospective study including CD patients who received UST from September 2015 to January 2017. Patients received 90 mg of UST subcutaneously at weeks 0, 4, and 12, then every 8 weeks. Two cohorts of patients were analyzed: an induction cohort and a maintenance cohort. We evaluated clinical, biological, and imaging/endoscopic response to UST treatment. UST trough levels and anti-UST antibodies were dosed at weeks 12 and 28 in the induction cohort, and at a single time point in the maintenance cohort. RESULTS: Forty-nine patients were enrolled in the maintenance cohort. Mean concentrations of UST were 1.88 ± 1.40 µg/mL. UST trough levels were not significantly different in patients with or without clinical, biological, or imaging/endoscopic responses to UST treatment (p > 0.11). Twenty-three consecutive patients were included in the induction cohort. At week 12, mean UST concentrations were 1.45 ± 1.15 µg/mL. Patients with a biological response to UST treatment had significant higher serum UST trough concentration (median 1.72 µg/mL) than non-responders (median 0.56 µg/mL, p = 0.02). A UST trough level ≥ 1.10 µg/mL at week 12 was associated with a biological response to UST treatment at 6 months. CONCLUSION: UST trough levels were associated with a biological response at the end of the induction phase. In patients with low levels of UST, optimization treatment may be necessary to obtain a sustained response.

Clinical relevance of innovative immunoassays for serum ustekinumab and anti-ustekinumab antibody levels in Crohn's disease.

BACKGROUND AND AIM: Ustekinumab is a human monoclonal antibody to the p40 subunit of human IL-12/IL-23. The purpose of this report is to verify the newly developed immunoassays for serum ustekinumab and anti-ustekinumab antibody (AUA) concentrations and assess their clinical utility. METHODS: Serum ustekinumab trough levels and AUA levels were measured using new immunoassays in 38 patients with Crohn's disease under ustekinumab maintenance injection. RESULTS: Mean ustekinumab trough levels were 2.54 ± 2.1 µg/mL, and 3 of 38 patients (7.9%) were positive for AUAs. There was no association between ustekinumab trough levels and AUA levels. The optimal trough level of ustekinumab to maintain negative C-reactive protein levels (≤ 0.3 mg/dL) was 1.67 µg/mL determined by receiver operating characteristic curve analysis. Ustekinumab trough level negatively but significantly correlated with C-reactive protein, erythrocyte sedimentation rate, and Crohn's disease activity index and positively and significantly correlated with serum albumin levels. Ustekinumab trough levels were significantly higher in biologics-naïve patients than in biologics-experienced patients, although there was no difference in AUA levels. CONCLUSIONS: We developed new assays for serum ustekinumab trough and AUA levels. These assays might provide new insights into therapeutic drug monitoring-based management of Crohn's disease patients under ustekinumab therapy.

Concentrations of Ustekinumab During Induction Therapy Associate With Remission in Patients With Crohn's Disease.

Ustekinumab is approved for treatment of Crohn's disease (CD).1,2 Few data are available to assess the usefulness of monitoring inflammatory biomarkers and therapeutic drug monitoring to predict response to ustekinumab. We conducted a prospective study to assess the relationships between these parameters and the clinical outcome at week 16 in active CD patients receiving ustekinumab.

Usefulness and correlation with clinical response of serum ustekinumab levels measured at 6 weeks versus 12 weeks.

BACKGROUND: Monitoring serum drug levels has been proposed as a useful tool for improving and personalizing the management of psoriasis. However, in the case of ustekinumab the usefulness of such monitoring was not demonstrated when drug levels were measured at week 12. OBJECTIVES: To evaluate the correlation of serum ustekinumab levels measured at weeks 6 and 12 with clinical response. METHODS: In a prospective cohort study, we enrolled patients with psoriasis treated with ustekinumab 45 mg every 12 weeks for at least 24 weeks. We measured serum ustekinumab levels at weeks 6 and 12 in each patient. Using the absolute PASI score, response to treatment was defined as optimal (≤1), excellent (≤3), appropriate (>3 and ≤5), or inappropriate (>5). RESULTS: About 54 serum samples from 27 patients were analyzed. No correlation was found between serum drug levels and absolute PASI at week 12. At week 6, an inverse linear correlation was found (p = .0001). Moreover, serum levels at week 6 were higher in patients with optimal, excellent and appropriate responses than in patients with an inappropriate response. CONCLUSIONS: Assessment of ustekinumab serum levels at week 6 could provide useful information in routine clinical practice.

Drug Levels in the Maternal Serum, Cord Blood and Breast Milk of a Ustekinumab-Treated Patient with Crohn's Disease.

Ustekinumab [UST] therapy during pregnancy has not yet been extensively evaluated in patients with Crohn's disease. Here, we present the case of a 24-year-old woman with therapy-refractory Crohn's disease, who was treated with UST until Week 30 of pregnancy and successfully delivered a healthy baby boy, who had normal development in the follow-up period of one year. The cord blood UST level was markedly higher than the measured maternal serum drug level. The trough level in the breast milk after re-initiating postpartum UST therapy was initially in the same range as the corresponding serum trough level, and then decreased during maintenance therapy. This is one of the first reports describing the drug levels in the breast milk after re-initiating UST treatment in a Crohn's disease patient.

Subcutaneous rather than intravenous ustekinumab induction is associated with comparable circulating drug levels and early clinical response: a pilot study.

BACKGROUND: Ustekinumab (USK) is licenced for intravenous induction and subcutaneous (S/C) maintenance in Crohn's disease. AIM: To evaluate ustekinumab trough concentrations and clinical response with exclusive subcutaneous ustekinumab induction. METHODS: Patients with Crohn's disease who initiated treatment with subcutaneous ustekinumab at a single academic centre were included in this pilot study. A dosage of 360 mg ustekinumab was given subcutaneously in divided doses; 180 mg at Week 0, 90 mg at Week 1 and 90 mg at Week 2, with corresponding ustekinumab trough concentrations assessed to Week 8. The primary outcome measures were trough serum ustekinumab levels and clinical remission at Week 8. Secondary outcome measures were trough serum ustekinumab levels at Week 1 & 2 and changes in C-reactive protein, albumin and faecal calprotectin at Week 8. RESULTS: Nineteen patients were included. Median Week 8 ustekinumab trough concentrations were 6.1 µg/mL (Inter-quartile range 4-9.8 µg/mL). There was a significant improvement in Harvey Bradshaw index from Week 0 (median HBI 5; interquartile range 2-8) to Week 8 (median HBI 1; interquartile range 0-3) (P = 0.002). C-reactive protein levels did not change significantly but faecal calprotectin improved significantly; median faecal calprotectin at Week 0 was 533 µg/g; at Week 8, it was 278 µg/g (P = 0.038). CONCLUSIONS: Ustekinumab trough concentrations are comparable whether ustekinumab induction treatment was administered subcutaneously or intravenously. A significant improvement in symptoms and faecal calprotectin was noted. These results support the use of subcutaneous induction as an alternative if there are barriers to intravenous induction.

Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Therapeutic drug monitoring (TDM) has emerged as a useful tool to optimize the use of drug therapies in adults with inflammatory bowel disease (IBD), including both Crohn's disease (CD) and ulcerative colitis (UC), especially during the use of biological therapies, for which the pharmacokinetics and pharmacodynamics are highly variable among patients. Fewer data exist in children. This review examines the current literature on TDM in pediatric IBD. RECENT FINDINGS: Drug clearance is affected by a number of patient and disease factors. For thiopurines, adjusting dosing by monitoring 6-thioguanine (6TGN) and 6-methylmercaptopurine ((6MMP) levels is demonstrated to maximize response and minimize toxicity, while monitoring metabolite levels when treating with anti-tumor necrosis factor (anti-TNF) remain controversial. While in adults the use of TDM in the setting of loss of response to anti-TNF therapy is established, in children, only a small number of studies exist, but these too have encouraging results. There are however, conflicting data regarding the optimal timing of TDM, comparing "reactive" monitoring and "proactive" monitoring. No such data exist in pediatrics. TDM is cost-effective, and dose reduction may represent a safety benefit. There are limited adult data for use of TDM for the newer biologics, vedolizumab and ustekinumab, but early results suggest similarly promising utility. The use of TDM in pediatric IBD is increasing in clinical practice, with similar efficacy to adults demonstrated in children with loss of response to anti-TNF therapy. More prospective studies are needed in children to examine proactive monitoring and utility of TDM with newer biologics.

Ustekinumab Drug Levels in Maternal and Cord Blood in a Woman With Crohn's Disease Treated Until 33 Weeks of Gestation.

A 35-year old woman with ileocolonic, perianal, and vulval Crohn's disease was treated with subcutaneous ustekinuamb [USK] throughout pregnancy. Dose intervals were shortened from 6-weekly to 4-weekly to maintain clinical remission. The last dose of USK was administered at 33 weeks of gestation, and a healthy baby boy was delivered by caesarean section at 37 weeks. Maternal trough USK levels remained stable during pregnancy. Cord blood USK levels were nearly 2-fold higher than contemporaneous maternal serum levels. To our knowledge, this is the first report of maternal and cord USK levels in a patient with Crohn's disease.

Optimization of biologic therapy in Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a manifestation of inflammatory bowel disease (IBD), which can result in significant morbidity. Biologic therapy with anti-TNF medication has been effective in treating inflammation and reducing complications in CD. It is important for clinicians to have better knowledge of the various biologic therapies including mechanisms of action and optimization strategies. AREAS COVERED: The review describes optimization of biologic therapy in CD including different mechanisms of loss of response, therapeutic drug monitoring in CD, clinical implications and management strategies which utilize drug monitoring, and areas of future development and research in optimization of biologic therapy. EXPERT OPINION: Achieving adequate levels of the drug (antibody unbound) is one of the most important determinants of attaining clinical remission and mucosal healing. Drug level is also critical in determining if a patient requires combination therapy with an immunomodulator. Certain populations, including those with active perianal disease, may require higher serum levels to achieve healing or closure. Treat to target level is an algorithm that is not universally accepted and more data is need. Additionally, there are numerous assays that don't always correlate, especially regarding measuring anti-drug antibodies.

Challenges in longitudinal exposure-response modeling of data from complex study designs: a case study of modeling CDAI score for ustekinumab in patients with Crohn's disease.

Informative exposure-response modeling of clinical endpoints is important in drug development to identify optimum dose and dosing regimens. Despite much recent progress in mechanism-based longitudinal modeling of clinical data, challenges remain in clinical trials of diseases such as Crohn's disease, where a commonly used composite endpoint Crohn's Disease Activity Index (CDAI) has considerable variation in its administration and scoring between different assessors and complex study designs typically include maintenance phases with randomized withdrawal re-randomizations and other response driven dose adjustments. This manuscript illustrates the complexities of exposure-response modeling of such composite endpoint data through a latent-variable based Indirect Response model framework for CDAI scores using data from three phase III trials of ustekinumab in patients with moderate-to-severe Crohn's Disease. Visual predictive check was used to evaluate model performance. Potential impacts of the study design on model development and evaluation of the E-R relationship in the induction and maintenance phases of treatment are discussed. Certain biases appeared difficult to overcome, and an autocorrelated residual error model was found to provide improvement.

Prolongation of Biologic Dosing Intervals in Patients With Stable Psoriasis: A Feasibility Study.

BACKGROUND: Biologics are usually licensed according to the "one dose fits all" principle. It is therefore suspected that a significant number of patients with psoriasis are overtreated. However, evidence for successful dose reduction of biologics in psoriasis is scarce. The aim of this study was to investigate whether the dosing interval of 3 biologics, adalimumab, etanercept, or ustekinumab could be prolonged successfully in patients with plaque psoriasis. METHODS: In a prospective exploratory cohort study, 59 patients with psoriasis on maintenance treatment with adalimumab, etanercept, or ustekinumab were included. After a run-in period of 6 weeks, the dosing interval of the biologics was prolonged according to a predefined schedule. Our primary objective was to determine the proportion of patients who could maintain a successful prolongation of the per label dosing interval. Secondary objectives were to evaluate the predictive value of baseline serum trough concentrations for successful dosing interval prolongation and to explore the feasibility of dosing interval prolongations in off-label-treated patients. RESULTS: In the per label group, 7 out of 16 (44%) adalimumab patients, 5 out of 16 (31%) etanercept patients, and 2 out of 10 (20%) ustekinumab patients achieved a successful dosing interval prolongation. Baseline serum trough concentrations did not differ significantly between patients with successful dosing interval prolongation and failures. In the off-label group, prolongation in patients with already extended intervals was unsuccessful. For patients with shortened intervals, minor prolongation was successful in 3 out of 17 (17.6%) patients. CONCLUSIONS: Prolongation of the per label biologic dosing interval was feasible in approximately 30% of patients with psoriasis with stable minimal disease activity and can reduce costs in clinical practice. Baseline serum trough concentrations were not predictive for successful dosing interval prolongation.