Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Continuation of Anti-TNF in Patients With Ulcerative Colitis in Remission Is Not Cost-effective Compared With Treatment Withdrawal: A Markov Model.

BACKGROUND AND AIMS: Anti-tumour necrosis factor alpha [anti-TNF] treatment accounts for 31% of health care expenditures associated with ulcerative colitis [UC]. Withdrawal of anti-TNF in patients with UC in remission may decrease side effects and infections, while promoting cost containment. Approximately 36% of patients relapse within 12-24 months of anti-TNF withdrawal, but reintroduction of treatment is successful in 80% of patients. We aimed to evaluate the cost-effectiveness of continuation versus withdrawal of anti-TNF in patients with UC in remission. METHODS: We developed a Markov model comparing cost-effectiveness of anti-TNF continuation versus withdrawal, from a health care provider perspective. Transition probabilities were calculated from literature, or estimated by an expert panel of 11 gastroenterologists. Deterministic and probabilistic sensitivity analyses were performed to account for assumptions and uncertainty. The cost-effectiveness threshold was set at an incremental cost-effectiveness ratio of €80,000 per quality-adjusted life-year [QALY]. RESULTS: At 5 years, anti-TNF withdrawal was less costly [-€10,781 per patient], but also slightly less effective [-0.04 QALY per patient] than continued treatment. Continuation of anti-TNF compared with withdrawal costs €300,390/QALY, exceeding the cost-effectiveness threshold. Continued therapy would become cost-effective if the relapse rate following anti-TNF withdrawal was ≥43% higher, or if adalimumab or infliximab [biosimilar] prices fell below €87/40 mg and €66/100 mg, respectively. CONCLUSIONS: Continuation of anti-TNF in UC patients in remission is not cost-effective compared with withdrawal. A stop-and-reintroduction strategy is cost-saving but is slightly less effective than continued therapy. This strategy could be improved by identifying patients at increased risk of relapse.

Temporal Trends in Surgical Resection Rates and Biologic Prescribing in Crohn's Disease: A Population-based Cohort Study.

BACKGROUND: The use of biologic therapy for Crohn's disease [CD] continues to evolve, however, the effect of this on the requirement for surgery remains unclear. We assessed changes in biologic prescription and surgery over time in a population-based cohort. METHODS: We performed a retrospective cohort study of all 1753 patients diagnosed with CD in Lothian, Scotland, between January 1, 2000 and December 31, 2017, reviewing the electronic health record of each patient to identify all CD-related surgery and biologic prescription. Cumulative probability and hazard ratios for surgery and biologic prescription from diagnosis were calculated and compared using the log-rank test and Cox regression analysis stratified by year of diagnosis into cohorts. RESULTS: The 5-year cumulative risk of surgery was 20.4% in cohort 1 [2000-2004],18.3% in cohort 2 [2005-2008], 14.7% in cohort 3 [2009-2013], and 13.0% in cohort 4 [2014-2017] p <0.001. The 5-year cumulative risk of biologic prescription was 5.7% in cohort 1, 12.2% in cohort 2, 22.0% in cohort 3, and 44.9% in cohort 4 p <0.001. CONCLUSIONS: The increased and earlier use of biologic therapy in CD patients corresponded with a decreasing requirement for surgery over time within our cohort. This could mean that adopting a top-down or accelerated step-up treatment strategy may be effective at reducing the requirement for surgery in newly diagnosed CD.

Assessment of Body Weight Changes in Patients with Inflammatory Bowel Diseases Initiating Biologic Therapy: A Prospective Cohort Study.

BACKGROUND: Prior studies have inconsistently suggested that biologic therapy may be associated with weight gain in inflammatory bowel disease patients (IBD). Our aim was to compare weight gain across different biologic therapy classes with distinct mechanisms of action. METHODS: This prospective cohort study recruited patients with moderate to severe IBD initiating outpatient biologic therapy with anti-TNF (infliximab, adalimumab), vedolizumab, or ustekinumab. Weight measurements were performed at weeks 0, 14, 30, and 54. Changes in weight between baseline and each of the follow-up visits were modeled as a continuous variable, and multivariate regression assessed the independent effect of therapeutic class on this outcome. RESULTS: Our study enrolled 269 patients (163 CD, 106 UC) initiating biologic therapy [99 anti-TNF (37%), 122 vedolizumab (45%), 48 ustekinumab (18%)]. From baseline, the weight significantly increased at week 14 with a mean of 0.36 kg (± 3.8 kg, p = 0.004) and continued to increase compared to baseline with 0.96 kg (± 3.9 kg, p < 0.001) and 1.29 kg (± 4.2 kg, p < 0.001) at week 30 and 54, respectively. On univariate and multivariable analysis, no significant differences between any of the biologic therapies for weight gain were seen at any time point (weight gain anti-TNF: 0.31 kg, 1.06 kg, 1.33 kg; VDZ: 0.30 kg, 0.83 kg, 1.10 kg; UST: 0.63 kg, 1.21 kg, 2.31 kg at wk 14, wk 30, and wk 54, respectively). None of the disease activity parameters showed any statistical association with weight gain. CONCLUSION: There was no difference in weight gain among the different biologic therapeutic classes.

Improved effectiveness from individualized dosing of self-administered biologics for the treatment of moderate-to-severe psoriasis: a 5-year retrospective chart review from a Spanish University Hospital.

Background: Biologics for moderate-to-severe psoriasis are expensive and treatment substitutions may vastly increase cost. Moreover, administration regimens in routine practice may differ from recommended guidelines.Objectives: To evaluate long-term effectiveness, regimen, drug-survival, and efficiency of self-administered biologics in clinical practice.Methods: We performed a 5-year retrospective study in 72 patients (44 ± 14 years old) with moderate-to-severe psoriasis at the University Hospital La Plana (Vila-real, Spain), treated with subcutaneous biologics. We determined the effectiveness (PASI 75 or PASI < 5), and drug-survival using Kaplan-Meier estimates, and analyzed reasons for treatment interruption, drug substitution patterns, and costs.Results: Etanercept was less effective (45%) than ustekinumab (85%) and adalimumab (71%). In 15% of patients, optimal responses were maintained despite dose intervals lengthening. Drug-survival was significantly lower for etanercept than for the other biologics (p < .005). Most adalimumab and etanercept discontinuations were due to adverse events or lack of effectiveness; for ustekinumab the causes were unrelated to drug effects. Ustekinumab was 100% effective as a secondary biologic.Conclusion: Ustekinumab was the safest and most efficient treatment. Etanercept showed the highest treatment failure rate, incurring higher costs. Dosage individualization according to patient needs improves the therapy efficiency, reducing therapeutic failure and derived costs.

A Cost-per-Number Needed to Treat Analysis Assessing the Efficiency of Biologic Drugs in Moderate to Severe Plaque Psoriasis. / Evaluación de la eficiencia de los tratamientos biológicos en la psoriasis moderada a grave en España: análisis de coste por número necesario a tratar (NNT).

BACKGROUND AND OBJECTIVES: Psoriasis is a chronic inflammatory skin disease with an estimated prevalence in Spain of 2.3% of the population. Approximately 30% of patients have moderate-to-severe forms. Treatment with biologic agents is proving to be a step forward in the management of the disease, although these treatments are very expensive. The objective of this study was to determine the efficiency, in terms of cost per number needed to treat (NNT), of the biologic drugs available in Spain for the treatment of moderate to severe plaque psoriasis. METHODS: NNT data were obtained from a network meta-analysis that included all randomized clinical trials of biologic drugs sold in Spain. The cost of each treatment was calculated based on the approved dosage for the first year of treatment, as indicated in the Summary of Product Characteristics. These data were used to calculate the cost per NNT of the drugs for various PASI scores (75, 90, and 100). A sensitivity analysis was performed taking into consideration only the PASI-response measurement time (after 10, 12, or 16 weeks, depending on the drug). RESULTS: The order of efficiency, from most to least efficient, in the case of a PASI 75 response was ixekizumab > ustekinumab 45mg > ustekinumab 90mg > secukinumab > infliximab > etanercept > adalimumab. The order for PASI 90 was ixekizumab >secukinumab >ustekinumab 45mg > ustekinumab 90mg > infliximab > adalimumab > etanercept. The order for PASI 100 was ixekizumab > secukinumab > infliximab > ustekinumab 90mg > ustekinumab 45mg > adalimumab > etanercept. The sensitivity analysis showed some changes in the order, depending on the response-assessment period. CONCLUSIONS: The findings show a link between the efficacy of the biologic therapies available in Spain for the treatment of moderate-to-severe plaque psoriasis and their efficiency. Ixekizumab had the lowest cost per NNT for all PASI-response scores (75, 90, and 100) during the first year of treatment.

Dose increase beyond labelled dose of biologics is associated with incremental pharmacy costs: results from a real-world study in the UK.

Background: There is limited evidence regarding biologics dosing patterns and its costs among psoriasis patients in the United Kingdom (UK). Objective: This retrospective study assessed biologics dose increase beyond labelled dose and associated UK pharmacy costs in moderate to severe psoriasis patients. Methods: Adult psoriasis patients on biologic prescription for ≥12 continuous months between January 2010 and March 2015 with their diagnosis recorded in the UK Hospital Treatment Insights Database within one month of such prescription were included. The proportion of patients receiving ≥30% higher the average daily maintenance dose as per the UK product label, and associated 12-month costs were reported. Results: The study included 362 patients, receiving adalimumab (48%), etanercept (17%), ustekinumab (12%), and infliximab (23%). Beyond labelled dose increase was noted in 14% adalimumab, 20% etanercept, 18% ustekinumab and 28% infliximab patients with an associated mean annual extra cost per patient of £7936, £5912, £2422 and £2275, respectively. Conclusion: Dose increase beyond labelled dose of biologics was commonly observed in moderate to severe psoriasis in the UK and resulted in substantial annual incremental pharmacy costs.

Tight controlled dose reduction of biologics in psoriasis patients with low disease activity: a randomized pragmatic non-inferiority trial.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disorder for which several targeted biologic therapies became available in the last 10 years. Data from patients with rheumatoid arthritis revealed that dose tapering combined with tight control of disease activity is successful. For psoriasis patients the lowest effective dose of biologics needs to be determined. The objective was to assess whether dose tapering of biologics guided by Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI) scores in psoriasis patients with controlled disease activity is non-inferior (NI) to usual care. METHODS/DESIGN: This is a multicenter, pragmatic, randomized, non-inferiority trial with cost- effectiveness analysis. One hundred and twenty patients with stable low disease activity (PASI ≤ 5 and DLQI ≤ 5) for at least 6 months with a stable use of adalimumab, etanercept or ustekinumab will be randomized 1:1 to the dose reduction group or usual care. In the dose reduction group, the treatment intervals will be prolonged stepwise, resulting in a 33% and 50% dose reduction, respectively. Disease activity is monitored every three months with PASI and DLQI. In case of flare the treatment is adjusted to the previous effective dose. The primary outcome (PASI) at 12 months will be analyzed with ANCOVA in which the baseline PASI will be included as covariate to gain efficiency. The secondary outcomes include number of and time to disease flares, health-related quality of life, serious adverse events, and costs. DISCUSSION: With this study we want to assess whether disease activity guided dose reduction of biologics can be achieved for psoriasis patients with low stable disease activity, without losing disease control. By using the lowest effective dose of biologics, we expect to minimize side effects and save costs. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov ( NCT 02602925 ). Trial registration date October 9 2015.

Economic Impact of Above-Label Dosing with Etanercept, Adalimumab, or Ustekinumab in Patients with Psoriasis.

BACKGROUND: Patients with moderate-to-severe psoriasis may be treated with above-label doses of biologics in an attempt to optimize outcomes. Dose escalation will have an effect on the cost of treatment. OBJECTIVE: To examine costs related to above-label use of etanercept, adalimumab, and ustekinumab among patients with moderate-to-severe psoriasis. METHODS: A retrospective study was performed using a large U.S. claims database. Patients were included in the study if they were aged ≥ 18 years with a diagnosis of psoriasis (excluding psoriatic arthritis) and had at least 1 medication fill for etanercept, adalimumab, or ustekinumab between January 1, 2011, and June 30, 2012. In addition, patients were required to have continuous enrollment for 12 months before, and 18 months after, the first biologic use (index biologic) during the maintenance period (defined as the period following the induction period in which each agent was titrated to its recommended maintenance dose per label) and at least 1 prescription filled for the index biologic during the 18 months after the maintenance period. Extensive above-label use was defined as taking an above-label dose (at least 10% higher than indicated in the label) for ≥ 180 days over a 12-month period following the maintenance period. Percentages of patients with extensive above-label use, mean number of days of above-label use, and additional costs associated with extensive above-label use (abovelabel cost minus on-label cost) were examined. RESULTS: The study included 3,310 patients who started treatment with etanercept (n = 1,443), adalimumab (n = 1,447), or ustekinumab (n = 420). Extensive above-label use occurred in 20.0% of etanercept patients, 2.6% of adalimumab patients, and 14.8% of ustekinumab patients. The mean duration of extensive above-label use was roughly similar for the 3 biologics (mean days [±SD]: 282 [±55] for etanercept, 279 [±57] for adalimumab, and 305 [±43] for ustekinumab). Additional annual costs per patient because of extensive above-label use were $19,458 for etanercept, $18,972 for adalimumab, and $21,045 for ustekinumab. Total additional annual costs were $5,623,362 for etanercept, $701,964 for adalimumab, and $1,304,790 for ustekinumab. CONCLUSIONS: Psoriasis patients treated with etanercept, adalimumab, or ustekinumab had extensive above-label use over the 12-month follow-up period, which subsequently led to higher costs. DISCLOSURES: Novartis Pharmaceuticals Corporation sponsored this study and the resultant publication. BioScience Communications provided medical writing and editorial support, which was also funded by Novartis Pharmaceuticals Corporation. Feldman was engaged by Novartis Pharmaceuticals as a paid clinical expert and scientific advisor for this study. He has received research support and speaking and/or consulting fees from AbbVie, Advance Medical, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Caremark, Celgene, Eli Lilly, Galderma, GSK/Stiefel, Informa, Janssen, LEO Pharma, Merck, Merz, Mylan, National Biological, National Psoriasis Foundation, Pfizer, Qurient, Suncare Research, UpToDate, and Valeant; is the founder and majority owner of www.DrScore.com ; and is founder and part owner of Causa Research. Zhao, Herrera, Tian, and Li are employees of Novartis Pharmaceuticals. Zhou is a paid consultant for Novartis Pharmaceuticals and is an employee of KMK Consulting. Study concept and design were contributed by Feldman, Zhao, Herrera, and Li. Zhou and Li were responsible for data collection. Data were interpreted by Feldman and Zhao, with assistance from Zhou, Herrera, Tian, and Li. The manuscript was written primarily by Feldman and Zhao, with assistance from Zhou and Li. The manuscript was revised by Feldman and Zhao, assisted by Zhou, Herrera, Tian, and Li. Portions of this work were presented at the 34th Anniversary Fall Clinical Dermatology Conference in Las Vegas, Nevada, October 1-4, 2015.

Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: Results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]).

BACKGROUND: Comparing effectiveness of biologics in real-world settings will help inform treatment decisions. OBJECTIVES: We sought to compare therapeutic responses among patients initiating infliximab, adalimumab, or etanercept versus ustekinumab during the Psoriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: Proportions of patients achieving a Physician Global Assessment score of clear (0)/minimal (1) and mean decrease in percentage of body surface area with psoriasis were evaluated at 6 and 12 months. Adjusted logistic regression (Physician Global Assessment score 0/1) and analysis of covariance (percentage of body surface area with psoriasis) were performed to determine treatment factors associated with effectiveness. RESULTS: Of 2541 new users on registry, 2076 had efficacy data: ustekinumab (n = 1041), infliximab (n = 116), adalimumab (n = 662), and etanercept (n = 257). Patients receiving tumor necrosis factor-alpha(-α) inhibitors were significantly less likely to achieve Physician Global Assessment score 0/1 versus ustekinumab (infliximab [odds ratio {OR} 0.396, P < .0001], adalimumab [OR 0.686, P = .0012], etanercept [OR 0.554, P = .0003] at 6 months and infliximab [OR 0.449, P = .0040] at 12 months). Mean decrease in percentage of body surface area with psoriasis was significantly greater for ustekinumab versus adalimumab (point estimate 1.833, P = .0020) and etanercept (point estimate 3.419, P < .0001) at 6 months and versus infliximab (point estimate 3.945, P = .0005) and etanercept (point estimate 2.778, P = .0007) at 12 months. LIMITATIONS: Treatment selection bias and limited data for doing adjustments are limitations. CONCLUSIONS: In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-α inhibitors studied for the majority of comparisons at 6 and 12 months.

Efficiency of biological therapies in patients with moderate to severe psoriasis: impact of a pharmacotherapeutic protocol.

BACKGROUND: It is not clear how to best use biologics in the treatment of psoriasis. Our objective was to assess use of a protocol for biological therapies (BT) in psoriasis. METHODS: A consensus protocol was established that included the indications for BT and dose optimization. Patient's characteristics, effectiveness, and cost of BT were analyzed before and after the implementation with two cross-sectional studies to assess its impact. RESULTS: About 106 were treated before the protocol and 118 patients were treated after. After implementing the protocol, the dose was reduced in 43.4% of the patients receiving adalimumab, in 37.5% for etanercept, in 28.6% for infliximab, and in 14.7% for ustekinumab. No statistically significant differences were found in PASI score after the implementation of the protocol, except for the percentage of patients that achieved PASI 75 with ustekinumab, which was slightly higher. The global yearly savings achieved with the protocol implementation were 115,969 €. CONCLUSIONS: The protocol helped to increase the efficiency of BT, with decreasing doses of BT without affecting treatment effectiveness.

The cost-effectiveness of ustekinumab for moderate-to-severe psoriasis.

Given its chronicity and impact on quality of life, psoriasis is a costly disease. As new and better treatments are developed, the cost of treating psoriasis has risen. In this drug profile, the authors discuss ustekinumab, its pharmacokinetics, safety profile, and direct and indirect costs to determine its cost-efficacy. The authors searched PubMed with specific search phrases for clinical trials investigating this issue over 5 years. Eleven articles analyzed cost-effectiveness of ustekinumab, and the references of these articles were included. Studies limited to 12 weeks reported that ustekinumab may not be cost-effective as it has high cost per injection and is costly when loading doses are required. Studies that went beyond 12 weeks documented that, with ustekinumab's infrequent dosing, it is cost-effective during the maintenance period.

Dose Modification in Biologic Therapy for Moderate to Severe Psoriasis: A Descriptive Analysis in a Clinical Practice Setting.

INTRODUCTION: In biologic therapy, dose modification in carefully selected patients when psoriasis is in remission could reduce treatment costs and the risks associated with drug exposure. MATERIAL AND METHODS: Observational, descriptive, crosssectional study, performed in January 2014, of 112 patients with moderate to severe psoriasis who had been on biologic therapy for at least 6 months. The therapeutic objective in all cases was to achieve and maintain a 75% reduction in Psoriasis Area and Severity Index (PASI 75). All the patients had started treatment with the standard regimen. During treatment, the dose had been reduced in patients who achieved the therapeutic objective and escalated in those who failed to respond adequately to standard doses. RESULTS: At the time of the study, 42.9% of the patients were receiving the standard dose, 50% were on a reduced dose, and 7.1% were on an escalated regimen. The agent with which the dose was most often reduced was adalimumab (57.7%), and the agents with which therapy was most often escalated were ustekinumab (17.9%) and infliximab (12.5%). Patients who received reduced doses had significantly longer-standing disease (P=.049) and longer treatment duration with the same biologic agent (P=.009). In the group that did not fulfill the criteria for dose reduction, the proportion of patients with psoriatic arthritis was significantly higher (P=.023). Cost savings were as follows: 21.5% with adalimumab, 13.8% with etanercept, .9% with ustekinumab, and .55% with infliximab. CONCLUSIONS: Patients with longer-standing disease and longer treatment duration with the same biologic agent were significantly more likely to be candidates for dose reduction. The proportion of patients with psoriatic arthritis was greater in the group of patients who did not fulfill the conditions for dose reduction. The overall cost saving achieved using the dose modification algorithm described in this study was 13%. Controlled studies are needed to define the profile of the patients best suited for dose reduction strategies without loss of treatment efficacy.

Patterns of medication utilization and costs associated with the use of etanercept, adalimumab, and ustekinumab in the management of moderate-to-severe psoriasis.

BACKGROUND: Dose escalations of biologic agents may be attempted in the management of moderate-to-severe psoriasis. This has implications for the real-world cost of treatment. OBJECTIVE: To examine the utilization patterns and costs associated with the use of etanercept, adalimumab, and ustekinumab among patients with moderate-to-severe psoriasis. METHODS: This was a retrospective cross-sectional study. Patients with 2 or more medical claims with a diagnosis of psoriasis (excluding psoriatic arthritis) who were enrolled in large employer-sponsored health plans (including a pharmacy benefit) in the United States from January 2007 to March 2012 were identified and extracted from the MarketScan Commercial Encounters Database. Patients aged at least 18 years were required to have 2 or more pharmacy claims for etanercept, adalimumab, or ustekinumab; the index date was the first biologic fill date. Demographics and comorbidities were identified during the 1-year pre-index period, and medication utilization and costs were evaluated in the 1-year post-index period after a titration period according to the product prescribing information (2 weeks to 12 weeks). Medication utilization parameters such as dose escalation, dose reduction, persistence, switching, discontinuation, and restarts were assessed at 6, 9, and 12 months from the end of the dose titration window. RESULTS: A total of 4,309 patients were included with a mean average age of 46 years, and 55% were male. Fifty-seven percent of the patients were started on etanercept, 39% on adalimumab, and 5% on ustekinumab. Patients had substantial dose escalation rates (etanercept: 41%; adalim-umab: 37%; ustekinumab: 36%, P less than 0.05) and discontinuation rates (etanercept: 35%; adalimumab: 27%; ustekinumab: 16%, P less than 0.05) over the 12-month post-titration period. Many patients also restarted the same biologic (etanercept: 37%; adalimumab: 10%; ustekinumab: 6%, P less than 0.05) or switched to another biologic (etanercept: 15%; adalimumab: 10%; ustekinumab: 5%, P less than 0.05) over the 12-month post-titration period. The persistence rates over 12 months were 19%, 53%, and 71% for etanercept, adalimumab, and ustekinumab, respectively (P less than 0.05). Close to one-third of the patients at 6 months and 39% at 12 months postdose titration experienced a dose escalation. Approximately half of the patients who experienced a dose escalation also had a discontinuation or a dose reduction over the 12-month post-titration period. CONCLUSIONS: Over one-third of psoriasis patients experienced a dose escalation of their biologic agents, and most of the dose escalation occurred during the first 6 months. Restarting, switching, and discontinuing index biologics were also common.