Evaluation of Changes in Skin and Joint Outcomes and Associated Treatment Changes in Psoriatic Arthritis (PsA): Experience From the Corrona PsA/SpA Registry.

OBJECTIVE: To characterize skin severity and joint activity outcomes and associated treatment changes in patients with psoriatic arthritis (PsA) through 12 months of follow-up after enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry. METHODS: Patients ≥ 18 years of age with a diagnosis of PsA and a history of psoriasis between March 21, 2013, and September 30, 2016, were enrolled (n = 647). Demographics, clinical features, and treatment characteristics were collected and stratified by skin severity and joint activity. Change in joint and skin from enrollment to the 12-month visit was classified by change in category of Clinical Disease Activity Index (CDAI) or body surface area (BSA). Tests of association evaluated the relationship between changes in therapy and changes in skin severity and joint activity. RESULTS: Patients with improvement in both joint activity and skin severity saw the largest median reduction in both CDAI and BSA, while those who worsened in both had the greatest median increase in both CDAI and BSA. The majority of PsA patients (> 50%) had no change in skin severity regardless if they had reduced therapy (50%), no therapy changes (54%), or increased therapy (56%; P = 0.5875). However, there was a significant association between changes in therapy and changes in joint activity (P < 0.001). Patients who increased therapy were more likely to have improvement in joint activity (32%) compared to patients who reduced therapy (22%) or had no therapy changes (11%). CONCLUSION: The clinical implication for our findings suggests the assessment and incorporation of both skin and joint components may be advisable.

Understanding the association between skin involvement and joint activity in patients with psoriatic arthritis: experience from the Corrona Registry.

Objective: To compare the characteristics of patients with psoriatic arthritis among patient groups stratified by degree of skin and joint involvement, and to evaluate the relationship between skin severity and joint activity. Methods: Body surface area (BSA) and Clinical Disease Activity Index (CDAI) at enrolment were analysed. Patient characteristics were stratified by skin severity and joint activity. Baseline patient characteristics, clinical and disease characteristics and patient-reported outcomes were compared. The strength of the relationship of skin severity and joint activity was evaluated using methods for categorical variables (χ2 test, Cramer's V) and continuous variables (linear regression). Results: 1542 adult patients in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry enrolled between 21 May 2013 and 20 September 2016 were analysed. Most patients in the BSA >3%/CDAI moderate/high subgroup had worse clinical and patient-reported outcomes. A significant (p<0.001) modest association (Cramer's V=0.1639) between skin severity and joint activity was observed among all patients at enrolment. Patients with higher skin severity were two times more likely to have higher joint involvement (OR 2.27, 95% CI 1.71 to 3.01). A significant linear relationship between CDAI and BSA was observed. Effect modification showed this linear relationship was modified by age, gender, insurance, work status, current therapy, Health Assessment Questionnaire, Nail visual analogue scale, minimal disease activity, dactylitis count, patient-reported pain and fatigue. Conclusion: Skin severity is modestly correlated with joint activity, and patients with higher skin severity are two times more likely to have increased joint involvement. Clinicians need to address both skin severity and joint activity in treatment decisions.

Treatment patterns, adherence, and persistence among psoriasis patients treated with biologics in a real-world setting, overall and by disease severity.

PURPOSE: Describe treatment patterns by disease severity among biologic-treated psoriasis patients. MATERIALS AND METHODS: We selected our study cohort in the IQVIA PharMetrics Plus adjudicated claims database linked to Electronic Health Record data from Modernizing Medicine Data Services. Patients were classified as having mild, moderate, or severe psoriasis based on a hierarchy of available severity measures. Patients were followed for 360 days to assess combination therapy, therapy switching and restarting, adherence and persistence. RESULTS: The cohort comprised 2130 biologic-treated patients (mean age: 47.6 years; 45.4% female); 447 (21%) had available disease severity measures. Compared to patients with mild (N = 282) psoriasis, more patients with moderate (N = 116) or severe (N = 49) disease used combination therapy (21.3% vs. 34.5% and 32.7%, respectively), switched therapies (12.1% vs. 19.8% and 22.4%), and discontinued biologics (18.4% vs. 27.6% and 36.7%). Mean adherence was <75% by Medication Possession Ratio (MPR) (73.9%) and Proportion of Days Covered (PDC) (70.2%). Overall, 52.2% had a mean MPR >80%. Mean persistence to biologics was 297.6 days. Persistence and adherence decreased with increasing disease severity. CONCLUSIONS: Biologic-treated psoriasis patients had inadequate adherence (i.e., MPR <80%) and modest persistence to biologics, with moderate and severe patients demonstrating lower adherence and persistence than mild patients.

Treatment patterns among patients with psoriasis using a large national payer database in the United States: a retrospective study.

AIM: To characterize treatment patterns of psoriasis patients in a large US managed care database. MATERIALS AND METHODS: Adults with newly-diagnosed psoriasis were identified from July 3, 2006-August 31, 2014. Patients had continuous enrollment with medical and pharmacy benefits for ≥6 months prior to and ≥1 year following the index date. The index date was the point at which any of the following inclusion criteria were satisfied: first psoriasis diagnosis by a dermatologist, ≥ 2 psoriasis diagnoses ≥30 days apart, or a diagnosis of psoriasis followed by a claim for psoriasis therapy. Of primary interest was to measure and describe the following psoriasis treatment patterns: utilization rates, time to treatment discontinuation, and lines of therapy for various therapeutic classes of pharmacologic therapies. RESULTS: From the 128,308 patients identified, 53% were female, mean ± SD age was 50 ± 16 years, with median 3 years follow-up. Topicals were received by 86% of patients, non-biologic systemics by 13%, biologics by 6%, phototherapy by 5%, and 13% received no psoriasis-related medication. Median time from index to first treatment was 0 days for topical, 6 months for non-biologic systemic, and 6 months for biologic. Of those treated, first-line therapies included topical (95%), non-biologic systemic (4%), and biologic (2%). For those with second-line treatment, non-biologic systemic (71%) and biologic (30%) therapies were more common. The most common treatment pattern was topicals only (83%), while all other patterns comprised <5% of the treatment patterns observed. LIMITATIONS: Like other observational studies, limitations to consider when interpreting results include the 6-month pre-index period of no psoriasis or the psoriasis medication claim may not perfectly select only incident user of psoriasis medications, claims-based algorithms may not accurately represent true treatment patterns, absence of over-the-counter medications data, and having no trend analyses over time or between groups. CONCLUSIONS: While the majority of patients with psoriasis initiated a pharmacological therapy, a significant portion did not have a claim for any psoriasis medication. Topical treatments are the most commonly used treatments for psoriasis. Non-biologic systemic and biologic therapies were rarely used first line, but became more common in later lines of treatment.

Medication adherence and persistence in patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis: a systematic literature review.

PURPOSE: Proper adherence and persistence to medications are crucial for better quality of life and improved outcomes in rheumatoid arthritis (RA), psoriasis (PsO), and psoriatic arthritis (PsA). We systematically describe current adherence and persistence patterns for RA, PsO, and PsA, with a focus on biologics and identifying factors associated with adherence and persistence. PATIENTS AND METHODS: Using various databases, a systematic literature review of US-based studies published from 2000 to 2015 on medication adherence and persistence to biologics and associated factors was conducted among patients with RA, PsO, and PsA. RESULTS: Using the medication possession ratio or the percentage of days covered >80%, RA and PsO adherence rates for etanercept, adalimumab, and infliximab ranged from 16% to 73%, 21% to 70%, and 38% to 81%, respectively. Using the criteria of a ≥45-day gap, RA persistence rates for etanercept, adalimumab, and infliximab ranged from 46% to 89%, 42% to 94%, and 41% to 76%, respectively. In PsO, persistence rates for etanercept and adalimumab ranged from 34% to 50% and 50% to 62%, respectively. Similar persistence rates were observed in PsA. Experienced biologics users showed better adherence and persistence. Younger age, female gender, higher out-of-pocket costs, greater disease severity, and more comorbidities were associated with lower adherence and persistence rates. Qualitative surveys revealed that nonpersistence was partly due to perceived ineffectiveness and safety/tolerability concerns. CONCLUSION: Biologic adherence and persistence rates in RA, PsO, and PsA in the United States were low, with significant opportunity for improvement. Various factors - including decrease in disease severity; reduction of comorbidities; lower out-of-pocket costs; refilling at specialty pharmacies; and awareness of drug effectiveness, safety, and tolerability - can inform targeted approaches to improve these rates.

Ixekizumab Pharmacokinetics, Anti-Drug Antibodies, and Efficacy through 60 Weeks of Treatment of Moderate to Severe Plaque Psoriasis.

Ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, is efficacious for moderate to severe plaque psoriasis. We examined relationships between serum ixekizumab concentrations, treatment-emergent anti-drug antibodies (TE-ADAs), and efficacy during 60 weeks of treatment in a randomized, controlled, phase 3 study. Steady-state ixekizumab serum trough concentrations were rapidly achieved and associated with high clinical responses at week 12 with a starting dose of 160 mg followed by 80 mg every 2 weeks. During the long-term extension period dosage of 80 mg every 4 weeks, stable serum trough concentrations maintained high clinical responses through week 60. Most (82.6%, 308/373) patients never developed TE-ADA. In TE-ADA-positive patients (17.4%, n = 65), variations in ADA titers, neutralizing capacity, and persistence were observed. Fifty-six patients (15%) developed low or moderate maximum titers, with serum concentrations and efficacy comparable to those of TE-ADA-negative patients. Nine patients (2.4%) developed high titers, with variable individual clinical responses; four of these nine patients achieved at least PASI 75 at week 60. Median serum concentrations in the TE-ADA-high titer group were generally comparable to the median serum concentrations in the lower titer groups. For most patients, TE-ADA had a negligible impact on ixekizumab serum concentrations and efficacy. Clinicaltrials.gov: NCT01646177.

Healthcare resource utilization and costs among psoriasis patients treated with biologics, overall and by disease severity.

AIMS: To describe healthcare resource utilization (HCRU) and costs among biologic-treated psoriasis patients in the US, overall and by disease severity. MATERIALS AND METHODS: IQVIA PharMetrics Plus administrative claims data were linked with Modernizing Medicine Data Services Electronic Health Record data and used to select adult psoriasis patients between April 1, 2010 and December 31, 2014. Eligible patients were classified by disease severity (mild, moderate, severe) using a hierarchy of available clinical measures. One-year outcomes included all-cause and psoriasis-related outpatient, emergency department, inpatient, and pharmacy HCRU and costs. RESULTS: This study identified 2,130 biologic-treated psoriasis patients: 282 (13%) had mild, 116 (5%) moderate, and 49 (2%) severe disease; 1,683 (79%) could not be classified. The mean age was 47.6 years; 45.4% were female. Relative to mild psoriasis patients, patients with moderate or severe disease had more median all-cause outpatient encounters (28.0 [mild] vs 32.0 [moderate], 36.0 [severe]), more median psoriasis-related outpatient encounters (6.0 [mild] vs 7.5 [moderate], 8.0 [severe]), and a higher proportion of overall claims for medications that were psoriasis-related (28% [mild] vs 37% [moderate], 34% [severe]). Relative to mild psoriasis patients, patients with moderate or severe disease had higher median all-cause total costs ($37.7k [mild] vs $42.3k [moderate], $49.3k [severe]), higher median psoriasis-related total costs ($32.7k [mild] vs $34.9k [moderate], $40.5k [severe]), higher median all-cause pharmacy costs ($33.9k [mild] vs $36.5k [moderate], $36.4k [severe]), and higher median psoriasis-related pharmacy costs ($32.2k [mild] vs $33.9k [moderate], $35.6k [severe]). LIMITATIONS: The assessment of psoriasis disease severity may not have necessarily coincided with the timing of biologic use. The definition of disease severity prevented the assessment of temporality, and may have introduced selection bias. CONCLUSIONS: Biologic-treated patients with moderate or severe psoriasis cost the healthcare system more than patients with mild psoriasis, primarily driven by higher pharmacy costs and more outpatient encounters.

Improvements in psoriasis within different body regions vary over time following treatment with ixekizumab.

BACKGROUND: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17 A. OBJECTIVE: Examine the efficacy of ixekizumab in clearing psoriasis within different body regions. METHODS: Data from 3 placebo- (PBO) or PBO- and etanercept (ETN)-controlled trials were integrated. Patients with moderate-to-severe psoriasis were randomized to 12 weeks of PBO (UNCOVER-1, -2, -3, N = 792; UNCOVER-2, -3, N = 361), 50 mg ETN twice weekly (N = 740), or 80 mg ixekizumab every 2 (IXE Q2W; N = 1169; N = 736) or 4 weeks (IXE Q4W; N = 1165; N = 733) after a 160-mg starting dose. RESULTS: Mean percent improvements in regional Psoriasis Area and Severity Index (PASI) were noted at Week 1 and increased through Week 12 in the IXE Q2W (approved dosing regimen) group for each body region. Week 12 improvements were 91.4% (head/neck); 92.8% (trunk); 89.9% (arms); and 88.7% (legs) (all regions p < .001 vs. PBO). Mean regional PASI improvements at Week 12 were ≥84.2% for ixekizumab versus ≤70.9% for ETN in all regions (p < .001). Scaling and thickness reduced faster than erythema. CONCLUSIONS: Within 12 weeks of ixekizumab treatment, all signs of psoriasis across all body regions reached clinically meaningful improvements, with the head/neck and trunk responding quicker than psoriasis of the arms and legs, especially with reduced scaling and thickness.

Response to Tetanus and Pneumococcal Vaccination Following Administration of Ixekizumab in Healthy Participants.

BACKGROUND: Ixekizumab (IXE) is an interleukin (IL)-17A antagonist approved for the treatment of adults with moderate-to-severe psoriasis. OBJECTIVE: The objective of this study was to determine if the immune response to tetanus and pneumococcal vaccines in healthy subjects administered IXE was noninferior to control. METHODS: In a randomized, open-label, parallel-group study, adult subjects received vaccinations alone (N = 42, control) or in combination with 160 mg IXE subcutaneously 2 weeks prior to vaccination and 80 mg IXE on the day of vaccination (N = 41, IXE). Response to tetanus vaccination was defined as anti-tetanus antibodies ≥ 1.0 IU and a ≥ 1.5-fold increase if baseline was ≤ 1.0 IU or a ≥ 2.5-fold increase if baseline was > 1.0 IU. Response to pneumococcal vaccination was defined as a ≥ 2-fold increase from baseline in anti-pneumococcal antibodies against > 50% of the 23 serotypes. The primary outcomes were the percentages of patients with a response to the tetanus and pneumococcal vaccines 4 weeks after vaccination. A noninferiority analysis of IXE to control using a 40% margin was evaluated for the primary outcomes. Safety and pharmacokinetics were also assessed. RESULTS: IXE (38 completers) was noninferior to control (41 completers) based on the difference in the proportion of responders to tetanus [1.4%; 90% confidence interval (CI) - 16.6 to 19.2] and pneumococcal (- 0.8%; 90% CI - 12.9 to 11.0) vaccines. Twenty subjects (14 IXE, six control) reported 43 mild treatment-emergent adverse events. CONCLUSION: IXE does not suppress the humoral immune response to non-live vaccines and was well tolerated in healthy subjects. ClinicalTrial.gov identifier: NCT02543918.

Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis.

BACKGROUND: Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS: We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS: In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS: In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known. (Funded by Eli Lilly; UNCOVER-1, UNCOVER-2, and UNCOVER-3 ClinicalTrials.gov numbers NCT01474512, NCT01597245, and NCT01646177, respectively.).

A cost savings approach to SPRED1 mutational analysis in individuals at risk for neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a clinically diagnosed autosomal dominant disorder requiring routine clinical management, particularly during the pediatric years. An overlapping disorder, Legius syndrome, at times is clinically indistinguishable from NF1 and results in a small percentage of individuals being mischaracterized. Distinguishing these two entities is increasingly important for prognosis, reproductive planning, and clinical management. The goal of our study was to evaluate the cost impact of genetic testing for patients with solely pigmentary findings. The costs of genetic testing in patients aged 1.5-18 years were modeled using a simulated population, assuming the clinical management approach of a single NF1 clinic. Two genetic testing algorithms (SPRED1 testing alone, and NF1 mutation analysis with reflex to SPRED1) were compared against a baseline of no genetic testing. The cost for SPRED1 mutation analysis for each individual meeting NF1 diagnostic criteria without neoplastic or boney manifestation, when compared to the no-testing approach with routine follow-up mutations between the ages of 10 and 14 years, was minimal (range of $4-$16). Based on the clinical practice of one NF1 clinic, we found that the cost difference to perform SPRED1 mutation analysis on individuals who meet diagnostic criteria for NF1 without neoplastic or boney manifestation were minimal. Therefore it is important that "when to test decisions" remain a physician/patient discussion, as individual benefits may be greatest at a different age than when it is most cost efficient.

Fatty metastatic lesions in 2 patients with renal clear-cell carcinoma.

This is a case report of 2 patients with previously resected renal cell carcinoma who present with unusual fatty lesions that proved to be metastases.