Treatment Patterns and Effectiveness of Tofacitinib in Patients Initiating Therapy for Rheumatoid Arthritis: Results From the CorEvitas Rheumatoid Arthritis Registry.

OBJECTIVE: This real-world analysis assessed baseline demographics/characteristics and treatment patterns/effectiveness in patients with rheumatoid arthritis (RA) initiating tofacitinib (TOF) in the US CorEvitas RA Registry. METHODS: The primary analysis of this study included patients with RA initiating TOF with a 12-month follow-up visit from November 2012 to January 2021. Outcomes included baseline demographics/characteristics and TOF initiation/discontinuation reasons, treatment patterns, and effectiveness (disease activity and patient-reported outcomes [PROs] at 12 months); the primary effectiveness outcome was Clinical Disease Activity Index low disease activity (CDAI LDA). All data, analyzed descriptively, were stratified by TOF regimen (monotherapy vs combination therapy), line of therapy (second- to fourth-line), time of initiation (2012-2014, 2015-2017, or 2018-2020), and dose (5 mg twice daily vs 11 mg once daily). RESULTS: Of 2874 patients with RA who initiated TOF, 1298 had a qualifying 12-month follow-up visit; of these, 43.1% were monotherapy and 66.5% were fourth-line therapy. Overall, tumor necrosis factor inhibitors (40.8%) were the most common treatment immediately prior to TOF initiation. The most common reason for TOF initiation (among those with a reason) was lack/loss of efficacy of prior treatment (67.7%). Overall, at 12 months, 31.9% and 10.1% had achieved CDAI LDA and remission, respectively; 22.4%, 10.4%, and 5% had achieved ≥ 20%, ≥ 50%, and ≥ 70% improvement in modified American College of Rheumatology core set measures, respectively; and improvements in PROs were observed. Effectiveness was generally similar across TOF stratifications. CONCLUSION: TOF effectiveness (CDAI LDA) was observed in a US real-world setting of patients with RA regardless of TOF regimen, line of therapy, time of initiation, and dose. (ClinicalTrials.gov: NCT04721808).

Adolescent and caregiver preferences for juvenile idiopathic arthritis treatment: a discrete-choice experiment.

BACKGROUND: This study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA). METHODS: We conducted a discrete-choice experiment among adolescents with JIA in the United States (US) (n = 197) and United Kingdom (UK) (n = 100) and caregivers of children with JIA in the US (n = 207) and UK (n = 200). In a series of questions, respondents chose between experimentally designed profiles for hypothetical JIA treatments that varied in efficacy (symptom control; time until next flare-up), side effects (stomachache, nausea, and vomiting; headaches), mode and frequency of administration, and the need for combination therapy. Using a random-parameters logit model, we estimated preference weights for these attributes, from which we derived their conditional relative importance. RESULTS: On average, respondents preferred greater symptom control; greater time until the next flare-up; less stomachache, nausea, and vomiting; and fewer headaches. However, adolescents and caregivers in the US were generally indifferent across varying modes and frequencies of administration. UK adolescents and caregivers preferred tablets, syrup, or injections to intravenous infusions. US and UK adolescents were indifferent between treatment with monotherapy or combination therapy; caregivers in the UK preferred treatment with combination therapy to monotherapy. Subgroup analysis showed preference heterogeneity across characteristics including gender, treatment experience, and symptom experience in both adolescents and caregivers. CONCLUSIONS: Improved symptom control, prolonged time to next flare-up, and avoidance of adverse events such as headache, stomachache, nausea, and vomiting are desirable characteristics of treatment regimens for adolescents with JIA and their caregivers.

Early Real-World Experience of Tofacitinib for Psoriatic Arthritis: Data from a United States Healthcare Claims Database.

INTRODUCTION: This study characterized real-world demographic and baseline clinical characteristics, as well as treatment persistence and adherence, in patients with psoriatic arthritis (PsA) who had newly initiated tofacitinib treatment. METHODS: This retrospective cohort study included patients aged 18 years or older in the IBM MarketScan™ US database with at least one tofacitinib claim (first = index) between December 14, 2017 and April 30, 2019; PsA diagnoses on/within 12 months pre-index; and no diagnoses of rheumatoid arthritis any time pre-index. Patients were continuously enrolled for 12 months pre-index and 6 months post-index, with no pre-index claims for tofacitinib. Patient demographic and clinical characteristics on the day of index, and history of advanced treatments (including tofacitinib monotherapy or combination therapy), were recorded. Outcomes at 6 months post-index included tofacitinib persistence (less than 60-day gap without tofacitinib treatment) and adherence (proportion of days covered [PDC] and medication possession ratio 80% or higher). RESULTS: Of the 10,354 patients with tofacitinib claims within the study period, 318 patients with PsA met the inclusion criteria. More than 60% of patients received tofacitinib monotherapy post-index, with a mean duration of PsA of 760.5 days at index. For patients who received tofacitinib combination therapy post-index, methotrexate was the most common concomitant conventional synthetic disease-modifying antirheumatic drug. At 6 months post-index, persistence was similar in patients receiving tofacitinib monotherapy (69.8%) versus combination therapy (73.1%); adherence (as measured by PDC ≥ 0.8) was numerically lower in patients receiving tofacitinib monotherapy (56.8%) versus combination therapy (65.5%). CONCLUSIONS: This analysis of US-based claims data described patients who had newly initiated tofacitinib treatment an average of 2 years after PsA diagnosis, with approximately two-thirds of patients receiving tofacitinib monotherapy. Observed rates of tofacitinib persistence were similar across patients who received tofacitinib monotherapy and combination therapy 6 months after initiation; adherence rates were numerically lower in patients receiving monotherapy.

Tofacitinib is a drug approved to treat patients with psoriatic arthritis (PsA) that has been shown to improve PsA symptoms and quality of life in controlled clinical trials. However, there is not much information on everyday use of tofacitinib outside of clinical trials in the USA. This study is one of the first to describe the characteristics of patients with PsA in the USA who take tofacitinib, including their typical age, sex, where they live, how long they have had PsA, and how they use tofacitinib. Use of tofacitinib included how patients followed tofacitinib prescription timings and dose (adherence) and how long they took tofacitinib for after it was prescribed (persistence). We used data collected from a US health insurance claims database (IBM MarketScan™) for patients with PsA and at least one claim for tofacitinib. In total, 318 patients were included and over 60% of them received tofacitinib therapy only (monotherapy; no conventional synthetic disease-modifying antirheumatic drug [csDMARD] therapy). For patients treated with both tofacitinib and a csDMARD (combination therapy), methotrexate was the most common drug prescribed. Six months after their first prescription of tofacitinib, around 70% of patients were still taking tofacitinib (monotherapy or combination therapy). However, a slightly lower number of patients taking tofacitinib monotherapy were taking it as originally instructed (adherence 57%), compared with those taking tofacitinib combination therapy (adherence 66%). Our results provide valuable information on the use of tofacitinib in US real-life settings outside of clinical trials and could help to improve the quality of care for patients with PsA.

Relationships of dermatologic symptoms and quality of life in patients with psoriatic arthritis: analysis of two tofacitinib phase III studies.

OBJECTIVES: Evaluate relationships between changes in dermatologic assessments and quality of life (QoL) measures; quantify dermatologic symptom severity impacts on QoL in patients with psoriatic arthritis (PsA) treated with tofacitinib. METHODS: Data were from two phase III studies; patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg every other week, or placebo advancing to tofacitinib 5 or 10 mg BID at Month 3. Repeated measures longitudinal models assessed relationships between dermatologic assessments (predictors) Itch Severity Item (ISI), Physician's Global Assessment of Psoriasis (PGA-PsO), and Patient's Global Joint and Skin Assessment-Visual Analog Scale-Psoriasis question (PGJS-VAS-PsO), and QoL measures (outcomes) Dermatology Life Quality Index (DLQI) and Short Form-36 Health Survey Version 2 (SF-36v2). Models included one predictor and one outcome. RESULTS: Direct, approximately linear relationships existed between predictors and outcomes. ISI/PGA-PsO/PGJS-VAS-PsO improvements from baseline of ≥3/≥2/≥40-mm VAS corresponded with clinically meaningful DLQI improvements; improvements from baseline of ≥4/≥3/≥40-mm VAS generally corresponded with clinically meaningful improvements across component scores and all SF-36v2 domains. CONCLUSIONS: Substantial links exist between dermatologic symptoms and QoL in patients with PsA, potentially informing patient-centered care and research. Rheumatologists should be aware of dermatologic manifestations and QoL impacts in patients with PsA. CLINICALTRIALS.GOV: NCT01877668; NCT01882439.

Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis.

BACKGROUND: Increases in lipid levels and cancers with tofacitinib prompted a trial of major adverse cardiovascular events (MACE) and cancers in patients with rheumatoid arthritis receiving tofacitinib as compared with a tumor necrosis factor (TNF) inhibitor. METHODS: We conducted a randomized, open-label, noninferiority, postauthorization, safety end-point trial involving patients with active rheumatoid arthritis despite methotrexate treatment who were 50 years of age or older and had at least one additional cardiovascular risk factor. Patients were randomly assigned in a 1:1:1 ratio to receive tofacitinib at a dose of 5 mg or 10 mg twice daily or a TNF inhibitor. The coprimary end points were adjudicated MACE and cancers, excluding nonmelanoma skin cancer. The noninferiority of tofacitinib would be shown if the upper boundary of the two-sided 95% confidence interval for the hazard ratio was less than 1.8 for the combined tofacitinib doses as compared with a TNF inhibitor. RESULTS: A total of 1455 patients received tofacitinib at a dose of 5 mg twice daily, 1456 received tofacitinib at a dose of 10 mg twice daily, and 1451 received a TNF inhibitor. During a median follow-up of 4.0 years, the incidences of MACE and cancer were higher with the combined tofacitinib doses (3.4% [98 patients] and 4.2% [122 patients], respectively) than with a TNF inhibitor (2.5% [37 patients] and 2.9% [42 patients]). The hazard ratios were 1.33 (95% confidence interval [CI], 0.91 to 1.94) for MACE and 1.48 (95% CI, 1.04 to 2.09) for cancers; the noninferiority of tofacitinib was not shown. The incidences of adjudicated opportunistic infections (including herpes zoster and tuberculosis), all herpes zoster (nonserious and serious), and adjudicated nonmelanoma skin cancer were higher with tofacitinib than with a TNF inhibitor. Efficacy was similar in all three groups, with improvements from month 2 that were sustained through trial completion. CONCLUSIONS: In this trial comparing the combined tofacitinib doses with a TNF inhibitor in a cardiovascular risk-enriched population, risks of MACE and cancers were higher with tofacitinib and did not meet noninferiority criteria. Several adverse events were more common with tofacitinib. (Funded by Pfizer; ORAL Surveillance ClinicalTrials.gov number, NCT02092467.).

Itch as Major Mediator of Effect of Tofacitinib on Health-Related Quality of Life in Psoriatic Arthritis: A Mediation Analysis.

Patients with psoriatic arthritis (PsA) experience impaired health-related quality of life (HRQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA, which has been associated with improvements in dermatologic endpoints in patients with PsA. To assess the extent to which tofacitinib affects patient HRQoL via improvements in dermatologic symptoms, including itch, data were pooled from patients with PsA who received tofacitinib in phase III studies (NCT01866668 and NCT01882439). Mediation modeling assessed the indirect effects (via Itch Severity Item [ISI] and Physician's Global Assessment of Psoriasis [PGA-PsO]) and direct effects (via all other factors) of tofacitinib treatment on dermatology-specific HRQoL (measured by Dermatology Life Quality Index [DLQI]). In the initial model, the treatment effect on DLQI was largely mediated by itch (ISI; p < 0.0001) and PGA-PsO (p < 0.01). The model was re-specified to assess the indirect effects only of itch and PGA-PsO on DLQI. Here, 17.7% of the treatment effect on DLQI was attributable to PGA-PsO (p = 0.0006), and 82.3% to itch (p < 0.0001). Tofacitinib-dependent improvements in DLQI were primarily mediated by itch relief, in addition to improvements in PGA-PsO.

Efficacy and safety of tofacitinib modified-release 11 mg once daily plus methotrexate in adult patients with rheumatoid arthritis: 24-week open-label phase results from a phase 3b/4 methotrexate withdrawal non-inferiority study (ORAL Shift).

OBJECTIVES: To report the efficacy, safety and patient-reported outcome measures (PROs) of tofacitinib modified-release 11 mg once daily plus methotrexate in patients with rheumatoid arthritis (RA) from the open-label phase of Oral Rheumatoid Arthritis Trial (ORAL) Shift. METHODS: ORAL Shift was a global, 48-week, phase 3b/4 withdrawal study in patients with moderate to severe RA and an inadequate response to methotrexate. Patients received open-label tofacitinib modified-release 11 mg once daily plus methotrexate; those who achieved low disease activity (LDA; Clinical Disease Activity Index (CDAI)≤10) at week 24 were randomised to receive blinded tofacitinib 11 mg once daily plus placebo (ie, blinded methotrexate withdrawal) or continue with blinded tofacitinib 11 mg once daily plus methotrexate for another 24 weeks. Efficacy, PROs and safety from the open-label phase are reported descriptively. RESULTS: Following screening, 694 patients were enrolled and received tofacitinib plus methotrexate in the open-label phase. At week 24, 527 (84.5%) patients achieved CDAI-defined LDA. Improvements from baseline to weeks 12 and 24 were generally observed for all efficacy outcomes (including measures of disease activity, and response, LDA and remission rates) and PROs. Adverse events (AEs), serious AEs and discontinuations due to AEs were reported by 362 (52.2%), 20 (2.9%) and 41 (5.9%) patients, respectively. No deaths were reported. CONCLUSIONS: Tofacitinib modified-release 11 mg once daily plus methotrexate conferred improvements in disease activity measures, functional outcomes and PROs, with most (84.5%) patients achieving CDAI-defined LDA after 24 weeks of open-label treatment; the safety profile was generally consistent with the historic safety profile of tofacitinib.Funded by Pfizer Inc; NCT02831855.

Impact of baseline body mass index on the efficacy and safety of tofacitinib in patients with psoriatic arthritis.

OBJECTIVES: This post-hoc analysis explored the impact of body mass index (BMI) on tofacitinib efficacy/safety in patients with active psoriatic arthritis (PsA). METHODS: Data were pooled from two phase 3 studies (NCT01877668; NCT01882439). Analyses included patients randomised to tofacitinib 5/10 mg twio times a day or placebo, stratified by baseline BMI: <25 kg/m2, ≥25-<30 kg/m2, ≥30-<35 kg/m2 or ≥35 kg/m2. Endpoints (month 3): American College of Rheumatology (ACR20/50/70), Health Assessment Questionnaire-Disability Index (HAQ-DI) and Psoriasis Area and Severity Index (PASI) 75 response rates; dactylitis/enthesitis resolution rates; changes from baseline Short Form-36 Health Survey version 2 (SF-36v2) Physical/Mental Component Summary (PCS) scores and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score. Safety was also reported. RESULTS: Analysis included 710 patients; 43.8% were obese (BMI ≥30 kg/m2). Tofacitinib demonstrated higher efficacy response rates at month 3, compared with placebo, regardless of baseline BMI. Generally, ACR20/50/70 and HAQ-DI response rates, enthesitis resolution rates and changes from baseline in SF-36v2 PCS score and FACIT-F total score (month 3) were reduced in patients with baseline BMI ≥35 kg/m2 versus patients with lower BMIs. Elevated alanine aminotransferase/aspartate aminotransferase levels were reported in patients with baseline BMI ≥35 kg/m2 receiving tofacitinib 5 mg but not 10 mg two times a day. CONCLUSION: Tofacitinib demonstrated greater efficacy than placebo in patients with PsA, regardless of baseline BMI. For all treatment arms, reduced efficacy was observed in patients with baseline BMI ≥35 kg/m2. Safety was generally comparable across BMI categories, although the effect of tofacitinib on liver enzymes in patients with baseline BMI ≥35 kg/m2 was inconclusive.

Characterization of Patients with Psoriasis in Challenging-to-Treat Body Areas in the Corrona Psoriasis Registry.

BACKGROUND: Real-world studies evaluating patients with challenging-to-treat localizations of psoriasis (scalp, nail, and palmoplantar) are limited. OBJECTIVE: To characterize patients with versus without psoriasis in challenging-to-treat areas seen in routine US clinical practice. METHODS: This retrospective observational study included all adult patients with psoriasis enrolled in the Corrona Psoriasis Registry between April 2015 and May 2018 who initiated a biologic therapy at registry enrollment. Patients were stratified by the presence of scalp, nail, or palmoplantar psoriasis (nonmutually exclusive groups). Patient demographics, clinical char-acteristics, disease activity, and patient-reported outcome measures (pain, fatigue, itch, EuroQol visual analog scale [EQ VAS], Dermatology Life Quality Index [DLQI], and Work Productivity and Activity Impairment questionnaire [WPAI]) were assessed at registry enrollment and compared between patients with versus without each challenging-to-treat area using nonparametric Kruskal-Wallis tests for continuous variables and χ2 or Fisher exact tests for categorical variables. Generalized linear regression models were used to estimate differences in disease activity and patient-reported outcomes between patients with versus without each challenging-to-treat area. RESULTS: Among 2,042 patients with psoriasis (mean age [±SD], 49.6 ± 14.7 years; 51.5% male), 38.4% had psoriatic arthritis (PsA), 38.1% had scalp psoriasis, 16.0% had nail psoriasis, 10.9% had palmoplantar psoriasis, and 26.2% had a combination of ≥2 challenging-to-treat areas and PsA; only 34.2% had body plaque psoriasis without PsA or challenging-to-treat areas. Patients in all challenging-to-treat groups reported higher (mean [95% CI]) itch (scalp, 58.01 [57.62-58.40] vs. 54.35 [53.99-54.72]; nail, 56.42 [56.02-56.81] vs. 55.59 [55.20-55.97]; palmoplantar, 60.22 [59.86-60.59] vs. 55.15 [54.79-55.54]) and lower EQ VAS (scalp, 68.12 [67.78-68.48] vs. 69.46 [69.12-69.81]; nail, 66.21 [65.89-66.55] vs. 69.48 [69.14-69.83]; palmoplantar, 66.21 [66.07-66.75] vs. 69.29 [68.94-69.94]) scores than those without the respective challenging-to-treat localization. Patients with nail or palmoplantar psoriasis reported higher pain, fatigue, and DLQI scores than those without. Higher proportions of patients with scalp or palmoplantar psoriasis reported work impairment compared with those without. CONCLUSION: Two-thirds of patients with psoriasis who initiated biologic therapy had PsA and/or ≥1 challenging-to-treat area. Patients with challenging-to-treat areas had worse patient-reported outcome scores than those without, indicating a significant burden of challenging-to-treat areas on patients' quality of life.

Secukinumab rapidly improves EQ-5D health status in patients with psoriasis: Pooled analysis from four phase 3 trials.

BACKGROUND: Patients with psoriasis experience decreased health-related quality of life due to physical and psychological burdens. OBJECTIVE: To assess the effect of a highly effective psoriasis treatment (secukinumab) on domains of the 3-level EuroQol 5 Dimensions questionnaire (EQ-5D-3L) in patients with moderate-to-severe psoriasis who reported problems at baseline. METHODS: This pooled analysis of four phase 3 clinical trials (ERASURE [NCT01365455], FIXTURE [NCT01358578], FEATURE [NCT01555125], and JUNCTURE [NCT01636687]) included patients with moderate-to-severe psoriasis randomized to receive placebo or secukinumab 300 mg and who reported problems in the EQ-5D-3L domains of mobility, self-care, usual activities, pain/discomfort, or anxiety/depression at baseline. Percentage of patients reporting problems in each domain were compared at Weeks 4, 8, and 12 between patients receiving secukinumab 300 mg and placebo. RESULTS: At baseline, 570 patients receiving secukinumab 300 mg and 579 receiving placebo reported ≥1 problem in the EQ-5D-3L domains. Patients receiving secukinumab 300 mg reported improvements in all 5 domains at Weeks 4, 8, and 12 compared with placebo (all p < .0001). CONCLUSION: These findings provide additional evidence of the quality-of-life impairment in patients with moderate-to-severe psoriasis and highlight the improvement across all EQ-5D-3L domains among patients treated with secukinumab.

Prediction of early clinical response in patients receiving tofacitinib in the OCTAVE Induction 1 and 2 studies.

INTRODUCTION: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Outcome prediction based on early treatment response, along with clinical and laboratory variables, would be very useful for clinical practice. The aim of this study was to determine early variables predictive of responder status in patients with UC treated with tofacitinib. METHODS: Data were collected from patients treated with tofacitinib 10 mg twice daily in the OCTAVE Induction 1 and 2 studies (NCT01465763 and NCT01458951). Logistic regression and random forest analyses were performed to determine the power of clinical and/or laboratory variables to predict 2- and 3-point partial Mayo score responder status of patients at Weeks 4 or 8 after baseline. RESULTS: From a complete list of variables measured in OCTAVE Induction 1 and 2, analyses identified partial Mayo score, partial Mayo subscore (stool frequency, rectal bleeding, and Physician Global Assessment), cholesterol level, and C-reactive protein level as sufficient variables to predict responder status. Using these variables at baseline and Week 2 predicted responder status at Week 4 with 84-87% accuracy and Week 8 with 74-79% accuracy. Variables at baseline, Weeks 2 and 4 could predict responder status at Week 8 with 85-87% accuracy. CONCLUSION: Using a limited set of time-dependent variables, statistical and machine learning models enabled early and clinically meaningful predictions of tofacitinib treatment outcomes in patients with moderately to severely active UC.

Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: This post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson's Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients. RESULTS: Across csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients. CONCLUSIONS: This analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients' perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009).

US real-world effectiveness of secukinumab for the treatment of psoriasis: 6-month analysis from the Corrona Psoriasis Registry.

Objective: To examine the real-world effectiveness of secukinumab with regard to clinical and patient-reported outcomes (PROs) from enrollment to a 6-month follow-up visit in patients with psoriasis in the Corrona Psoriasis Registry.Methods: Eligible patients aged ≥ 18 years who initiated secukinumab at enrollment in the Corrona Psoriasis Registry and had a 6-month follow-up visit (window: 5-9 months) as of December 31 2017, were included in the analysis. Measures of disease severity and PROs were assessed in patients who maintained secukinumab treatment at the 6-month follow-up visit.Results: Of the 144 patients who initiated secukinumab at enrollment and had a 6-month follow-up visit, 118 (81.9%) maintained secukinumab treatment at 6 months and demonstrated significant improvements in affected body surface area (BSA) and 5-point Investigator's Global Assessment (IGA) score (all p < .01). The majority of patients were biologic experienced (89.8%). In addition, patients reported significant improvements in quality of life, as well as in pain, itch, fatigue, work productivity, and daily activities (all p < .01).Conclusions: Secukinumab significantly improved disease severity and PROs after 6 months of follow-up in this real-world study, which is consistent with other current real-world studies.

Exploration of the Product of the 5-Point Investigator's Global Assessment and Body Surface Area (IGA × BSA) as a Practical Minimal Disease Activity Goal in Patients with Moderate-to-Severe Psoriasis.

BACKGROUND/AIMS: In the treat-to-target era, psoriasis disease activity measures that can be easily performed in routine clinical practice are needed. This retrospective pooled analysis explored cutoff values of the product of the 5-point Investigator's Global Assessment and percentage of affected body surface area (IGA × BSA) correlating with achievement of minimal disease activity (MDA). METHODS: Post hoc analysis of the phase 3 clinical trials ERASURE, FIXTURE, FEATURE, and JUNCTURE was conducted to determine associations between IGA × BSA and 2 MDA definitions (Psoriasis Area and Severity Index [PASI] 90 and Dermatology Life Quality Index [DLQI] 0/1, or PASI score ≤1 or BSA <3%) in patients with moderate-to-severe psoriasis receiving secukinumab 300 mg. For each definition of MDA, a range of possible cutoff values of IGA × BSA was examined at each time point. The optimal cutoff value was determined using Youden index (YI), calculated as (sensitivity + specificity - 1). RESULTS: For MDA defined as PASI 90 and DLQI 0/1, optimal IGA × BSA cutoffs were 2.10 at week 12 (YI, 0.60; sensitivity, 0.78; specificity, 0.82), 1.02 at week 24 (YI, 0.55; sensitivity, 0.73; specificity, 0.82), and 1.00 at week 52 (YI, 0.65; sensitivity, 0.79; specificity, 0.86). For MDA defined as PASI score ≤1 or BSA <3%, optimal IGA × BSA cutoffs were 2.98 at week 12 (YI, 0.91; sensitivity, 0.99; specificity, 0.92), 2.80 at week 24 (YI, 0.94; sensitivity, 0.99; specificity, 0.95), and 3.00 at week 52 (YI, 0.96; sensitivity, 1.00; specificity, 0.96). CONCLUSION: IGA × BSA could be a valid measure highly associated with achievement of MDA.

Health Care Utilization and Cost Associated with Biologic Treatment Patterns Among Patients with Moderate to Severe Psoriasis: Analyses from a Large U.S. Claims Database.

BACKGROUND: Discontinuation or switching of biologic treatment among patients with psoriasis imposes a great economic burden. OBJECTIVE: To assess the health care utilization and costs associated with nonswitchers, switchers, and discontinuers of biologics among patients with moderate to severe psoriasis. METHODS: Patients aged ≥ 18 years with ≥ 1 pharmacy claim for a biologic (adalimumab, etanercept, infliximab, and ustekinumab) between January 1, 2012, and June 30, 2015 (identification period), were identified in the Truven Health Analytics MarketScan Commercial and Medicare Supplemental databases. At the time of biologic initiation (index date), eligible patients were continuously enrolled with medical and pharmacy claims for ≥ 1 year before (baseline period) and ≥ 1 year after the index date (follow-up period). Patients had ≥ 1 psoriasis diagnosis and had no pharmacy claims for the index biologic during the baseline period. Patients were categorized into 3 mutually exclusive groups based on their biologic treatment pattern during the 1-year follow-up period: nonswitchers (patients who remained on their index biologic), switchers (patients who had a prescription for a biologic therapy other than their index biologic), and discontinuers (patients who had gaps in prescription claims [> 90 days for adalimumab, infliximab, and etanercept; > 120 days for ustekinumab]). Descriptive analyses were used to summarize baseline patient demographics, clinical characteristics, resource utilization, and health care costs (inflated to 2016 costs) across the 3 groups. Adjusted health care resource utilization and costs during the 1-year follow-up were estimated, controlling for age, sex, geographic region, insurance plan type, index drug, index year, Charlson Comorbidity Index score, resource utilization, total health care costs, and nonbiologic medications during the baseline period. RESULTS: Of the 8,710 patients with psoriasis included in the study, 5,000 (57.4%) were categorized as nonswitchers, 1,001 (11.5%) as switchers, and 2,709 (31.1%) as discontinuers. Emergency department and inpatient visits, respectively, were more common among switchers (adjusted incidence rate ratio [95% CI]: 1.10 [0.93-1.30] and 1.13 [0.84-1.53]) and discontinuers (1.50 [1.34-1.63] and 2.05 [1.70-2.48]) than among nonswitchers. Compared with nonswitchers, switchers had higher adjusted mean total health care costs (mean difference [95% CI]: $10,120 [$8,235-$12,033]), which were driven by increased prescription costs ($8,988 [$7,535-$10,610]) and medical costs ($2,746 [$1,090-$4,677]). Conversely, the adjusted mean total health care cost for discontinuers was lower than that for nonswitchers (mean difference [95% CI]: -$18,611 [-$20,254, -$17,025]) due to reduced prescription costs (-$20,486 [-$21,319, -$19,636]); however, discontinuers had a higher mean medical cost ($3,729 [$1,970-$5,527]). CONCLUSIONS: Switching or discontinuing biologics resulted in higher health care utilization and increased medical costs than remaining on the same biologic. These updated findings highlight the clinical and economic effects of discontinuing or switching biologic therapies in patients with psoriasis in clinical practice and may inform treatment and/or formulary decision making. DISCLOSURES: This study was sponsored by Novartis Pharmaceuticals Corporation. Feldman has received consulting, speaking, and/or research support from Novartis, AbbVie, Celgene, Sun Pharma, Janssen, Lilly, and Ortho. Tian and Germino are employees of Novartis. Wang was an employee of KMK Consulting and worked as a consultant for Novartis at the time of this study. Portions of this work were presented at the 2017 Fall Clinical Dermatology Conference; October 12-15, 2017; Las Vegas, NV; the 2017 Las Vegas Dermatology Seminar; November 2-4, 2017; Las Vegas, NV; and the 2018 American Academy of Dermatology Annual Meeting; February 16-20, 2018; San Diego, CA.