Sustained Improvements in Clinical and Patient-Reported Outcomes and Quality of Life Through 5 Years Among Ixekizumab-Treated Patients with Complete Clearance of Scalp Psoriasis by Week 60.

INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe plaque psoriasis. Since scalp psoriasis can be burdensome and challenging to treat with non-systemic therapies, this post hoc analysis focused on scalp psoriasis in patients with moderate-to-severe plaque psoriasis and baseline scalp involvement. The analysis considered a holistic concept of clearance through 5 years of ixekizumab treatment. METHODS: Ixekizumab-treated patients with baseline scalp involvement were pooled from three multicenter, randomized, double-blind, placebo-controlled, phase 3 trials (integrated UNCOVER-1/2 and UNCOVER-3). Analyses were performed on a subpopulation of patients who achieved complete resolution of scalp psoriasis at Week 60 (i.e., Week 60 Psoriasis Scalp Severity Index [PSSI-0] responders) and on the overall patient population (i.e., Week 60 PSSI-0 responders and non-responders), which was used as a reference. Clinical outcomes (PSSI), patient-reported outcomes (Itch Numeric Rating Scale [NRS] score, Skin Pain Visual Analogue Scale [VAS]), quality of life (Dermatology Life Quality Index [DLQI]), and concurrent outcomes were assessed from baseline through 5 years. Descriptive statistics of observed data were reported. RESULTS: After 60 weeks of ixekizumab treatment, 88.4% (UNCOVER-1/2) and 75.9% (UNCOVER-3) of patients with baseline scalp involvement achieved complete clearance (PSSI-0) of scalp psoriasis. Substantial improvements in the clinical outcomes (PSSI), patient-reported outcomes (Itch NRS, Skin Pain VAS), and quality of life (DLQI) were achieved by Week 60 and sustained through Week 264 in the Week 60 PSSI-0 responders and in the overall patient population. Additionally, a significant proportion of Week 60 PSSI-0 responders achieved concurrent complete scalp and skin clearance and quality of life improvement through 5 years. CONCLUSIONS: Continued treatment with ixekizumab provided long-term sustained scalp clearance over 5 years to patients with moderate-to-severe plaque psoriasis and baseline scalp involvement, and holistic improvements occurred across clinical outcomes, patient-reported outcomes, and quality of life. CLINICAL TRIAL NUMBERS: NCT01474512 (UNCOVER-1), NCT01597245 (UNCOVER-2), and NCT01646177 (UNCOVER-3).

Outcomes for Psoriasis by Self-Identified Racial Groups in Ixekizumab Clinical Trials: A Pooled Analysis.

BACKGROUND: Biologics have shown promising outcomes in psoriasis clinical trials. However, there is a paucity of data exploring the potential differences in outcomes between self-identified racial groups. OBJECTIVE: To evaluate treatment response to ixekizumab in patients with psoriasis across different self-identified racial subgroups. METHODS: This study analyzed pooled data from 5 clinical studies (UNCOVER-1, UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) with patients of different self-identified racial subgroups, who were treated with an on-label dose of ixekizumab for psoriasis through 12 weeks. Treatment response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and static Physician’s Global Assessment response rates. Patient Global Assessment of Disease Severity, Itch Numeric Rating Scale, Skin Pain Visual Analog Scale, and Dermatology Life Quality Index were used to evaluate the patient-reported outcomes (PROs) and impact on quality of life (QoL). RESULTS: A total of 1825 ixekizumab-treated patients from 5 pooled studies were included. Consistent with the clinical outcomes from the overall population, all self-identified racial groups showed rapid improvement in PASI through Week 12, although the response was somewhat slower in American Indian/Alaska Native patients. Differences in PROs and QoL assessments were observed among racial groups, especially in patients who identified as Black/African American and American Indian/Alaska Native. CONCLUSION: Ixekizumab is effective through 12 weeks of treatment for psoriasis across different self-identified racial groups. Sample sizes for some racial groups were small (N≤12), therefore, further research is required to understand potential differences in psoriasis treatment with ixekizumab between various racial groups.J Drugs Dermatol. 2024;23(2):17-22.  doi:10.36849/JDD.7672.

Speed and Cumulative Responses According to Body Regions in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Ixekizumab (Interleukin-17A Antagonist) versus Guselkumab (Interleukin-23p19 Inhibitor).

INTRODUCTION: When assessing the effect of a therapy for psoriasis (PsO), it is important to consider speed of response and cumulative response. However, responses among biologics may differ by body regions. This post hoc analysis compares speed of response and cumulative response for ixekizumab (IXE), an interleukin-17A antagonist, and guselkumab (GUS), an interleukin-23p19 inhibitor, in different body regions of patients with moderate-to-severe plaque PsO participating in the IXORA-R study, up to week 24. METHODS: The IXORA-R design has been previously described. Patients received the respective on-label dosing of IXE or GUS. The median time to first Psoriasis Area and Severity Index (PASI) 50, 75, 90, and 100 response (50%, 75%, 90%, and 100% improvement from baseline, respectively) and the cumulative days with clear skin for PASI 50, 75, 90, and 100 responses were assessed in four body regions: head, trunk, upper extremities, and lower extremities. RESULTS: A total of 1027 patients were enrolled and received IXE (N = 520) or GUS (N = 507). Median time to first PASI 50, 75, 90, and 100 response was shortest in the head region, followed by the remaining body regions in both IXE and GUS cohorts. In each body region, IXE was significantly faster than GUS (p < 0.001) in achieving PASI 50, 75, 90, and 100. Through 24 weeks, the number of days with clear skin for PASI 90 and 100 was greater in the head region, followed by trunk, upper extremities, and lastly lower extremities in both IXE and GUS cohorts. In each body region, through 24 weeks, patients on IXE experienced a significantly higher number of days with clear skin for PASI 50, 75, 90, and 100 than patients on GUS (p < 0.01). CONCLUSIONS: As compared to GUS, IXE provided a faster skin clearance and more days with clear skin in all body regions of patients with moderate-to-severe plaque PsO through 24 weeks. TRIAL REGISTRATION NUMBER: https://www. CLINICALTRIALS: gov/ : NCT03573323 (IXORA-R).

Psoriasis, a long-term, inflammatory skin disease, impacts patient's lives, and response to treatment varies depending on the body region affected. Here, we assessed the speed of response and cumulative response through 24 weeks in different body regions (head, trunk, upper extremities, and lower extremities) of patients with moderate-to-severe plaque psoriasis treated with currently approved therapies: ixekizumab (IXE), an interleukin-17A antagonist, or guselkumab (GUS), an interleukin-23p19 inhibitor. We calculated the speed of response as the number of weeks to achieve first skin clearance, based on the Psoriasis Area and Severity Index (PASI) tool, and the cumulative response as the number of days with clear skin throughout the 24-week period. We found that the head region achieved skin clearance fastest and had a higher number of days with clear skin compared to the trunk, upper extremities, and lower extremities, in both groups of patients treated with IXE or GUS. Compared to GUS, IXE provided faster skin clearance and a higher number of days with clear skin in all body regions. For example, the head region of patients treated with IXE, as compared to GUS, achieved complete skin clearance twofold faster and experienced 18.7% more days of complete skin clearance. In conclusion, treatment with IXE through 24 weeks provided a faster response and a higher cumulative response than treatment with GUS in all four body regions of patients with moderate-to-severe plaque psoriasis.

Network meta-analyses comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis at 24-28 and 48-52 weeks.

BACKGROUND: Available network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided comparisons up to 1 year. OBJECTIVE: We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP. METHODS: Bayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24-28 and 48-52. RESULTS: For the NMA at weeks 24-28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval [CrI] 35.2-58.0), followed by brodalumab (37.1%; 95% CrI 17.1-62.2) and bimekizumab (30.3%; 95% CrI 12.7-53.9). For the NMA at weeks 48-52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1-93.4), followed by adalimumab (75.6%; 95% CrI 61.5-87.3) and brodalumab (71.9%; 95% CrI 38.4-93.2). CONCLUSION: Among biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP.

Number Needed to Treat Network Meta-Analysis to Compare Biologic Drugs for Moderate-to-Severe Psoriasis.

INTRODUCTION: Number needed to treat (NNT) estimates are a practical metric to help identify the most effective therapies. Our objective is to compare 11 biologic drugs for moderate-to-severe psoriasis in terms of NNT. METHODS: The NNT data were obtained from a Bayesian network meta-analysis of 42 double-blind, randomized, phase 3 clinical trials for 11 biologics (adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab). We determined NNT to achieve Psoriasis Area and Severity Index (PASI) 75/90/100 responses at weeks 4, 8, 12, 16, and 48/52 and Dermatology Life Quality Index (DLQI) response 0, 1 at week 12. RESULTS: Highest efficacy (lowest NNT) was with brodalumab and ixekizumab for PASI 90 at weeks 4, 8, and 12; ixekizumab for PASI 90/100 at week 16; and brodalumab for PASI 100 at week 12. After 48/52 weeks, risankizumab had the highest efficacy for PASI 90/100 overlapping with guselkumab, brodalumab, and ixekizumab for PASI 90 and with brodalumab and ixekizumab for PASI 100. Ixekizumab had the highest efficacy for DLQI (0,1) at week 12. CONCLUSIONS: Brodalumab and ixekizumab had the lowest NNTs for achieving PASI responses at early time points and were not significantly different than risankizumab and guselkumab after 48/52 weeks.

Early Response is Associated With Stable Long-Term Response in Psoriasis Patients Receiving Ixekizumab or Ustekinumab.

BACKGROUND: The identification of early treatment factors that predict the long-term success of maintenance therapy for psoriasis may help optimize individual therapy. OBJECTIVE: To determine early treatment response rates to ixekizumab and ustekinumab and assess whether early response was associated with stable long-term response to these treatments in patients with moderate-to-severe psoriasis. METHODS: This post hoc subgroup analysis of the IXORA-S study (NCT02561806) measured disease severity using the Psoriasis Area Severity Index (PASI) and determined the percentage of patients treated with ixekizumab or ustekinumab who showed PASI 50 at week 2 or 4 (early response) and assessed whether early response was associated with maintaining complete (PASI 100) or almost complete (PASI 90) skin clearance at 80% of monthly visits during weeks 16−52 of treatment (stable response). Nonresponder imputation was used for missing PASI response status. RESULTS: A numerically higher portion of patients treated with ixekizumab were early responders and were significantly more likely to achieve a stable PASI 90 response (P<.0001) or PASI 100 response (P<.0001) than patients treated with ustekinumab. Patients treated with ixekizumab or ustekinumab who were early responders were more likely to achieve a stable response of PASI 90 or 100 (odds ratio>1). CONCLUSION: In patients with moderate-to-severe psoriasis treated with ixekizumab or ustekinumab, early response was a significant factor in maintaining stable complete or almost complete skin clearance. Therefore, rapid response is a clinically relevant factor to consider when optimizing individual therapeutic strategies. J Drugs Dermatol. 2022;21(2):122-126. doi:10.36849/JDD.6063.

Sustained High Efficacy and Favorable Safety Over Five Years in Patients With Burdensome Psoriasis (UNCOVER-1/UNCOVER-2).

BACKGROUND: Long-term efficacy, safety, and quality of life with ixekizumab (IXE) through 5 years in UNCOVER-1 and UNCOVER-2 patients with baseline scalp, nail, or palmoplantar psoriasis were assessed. METHODS: Patients included in this intent-to-treat subanalysis had baseline involvement in at least one of the three anatomic areas (scalp, fingernail, or palmoplantar locations) and 1) received IXE through week 60, with a 160-mg starting dose 80 mg Q2W through week 12 and Q4W thereafter, 2) achieved a static Physician’s Global Assessment score of 0 or 1 at week 12, and 3) completed week 60 and continued treatment with IXE Q4W or were escalated to Q2W during the long-term extension. Efficacy outcomes (e.g., percent improvement in Psoriasis Scalp Severity Index [PSSI], Nail Psoriasis Severity Index [NAPSI], Palmoplantar Psoriasis Area and Severity [PPASI], and Dermatology Life Quality Index [DLQI]) were summarized by descriptive statistics through week 264. RESULTS: Patients rapidly achieved and sustained improvements in scalp, nail, and palmoplantar psoriasis for up to 5 years with IXE. Patients achieved complete clearance at year 5: observed (scalp, 82%; nail, 73%; palmoplantar, 96%) and mNRI (scalp, 77%; nail, 67%; palmoplantar, 85%). Up to 80% of patients reported DLQI 0,1 responses at week 12, which were sustained through week 264. No increases in the number of annual treatment-emergent adverse events were observed from years 1–5. CONCLUSION: Patients receiving IXE for 5 years sustained high rates of improvement in scalp, nail, and palmoplantar psoriasis, with a long-term quality of life benefit with no unexpected safety signals. J Drugs Dermatol. 2021;20(8):880-887. doi:10.36849/JDD.6101.

Psoriasis Severity Assessment Combining Physician and Patient Reported Outcomes: The Optimal Psoriasis Assessment Tool.

INTRODUCTION: Psoriasis Area Severity Index (PASI) assessment is complex and time-consuming. A simpler assessment measure more sensitive to changes in symptom severity and predictive of patients' quality of life (Dermatology Life Quality Index, DLQI) is needed. This study aims to evaluate the Optimal Psoriasis Assessment Tool (OPAT) as an alternative to PASI. METHODS: This integrated analysis of three UNCOVER trials (NCT01474512, NCT01597245, and NCT01646177) randomized patients (N = 3866) with moderate-to-severe psoriasis to subcutaneously administered ixekizumab 80 mg Q2W or Q4W, or placebo or etanercept 50 mg Q2W. Pearson correlations were computed for clinical and patient-reported measures with PASI and DLQI. RESULTS: As the correlations with PASI and BSA were high and not much higher when adding severity, body surface area (BSA) was used for the clinical measure. BSA was the main measure influencing OPAT. Week 12 regression analyses results showed that PASI had a higher correlation with BSA combined with patient assessments than with BSA alone. Sensitivity analyses were also completed for PASI 75 and 90. For DLQI, correlations with the combined measures were even stronger than with BSA alone. A comprehensive model selection procedure was conducted, which illustrated that the two-term models are preferred. CONCLUSION: The OPAT is a simple and time-saving alternative to PASI. It can be derived using BSA and patient-reported assessments having strong correlation with PASI and moderate correlation with DLQI.

Dynamic Visual Representation of Clinical Efficacy of Ixekizumab in Psoriasis.

INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is an approved treatment for plaque psoriasis. This study aimed to use animated visualizations as a tool to simplify complex data from ixekizumab clinical trials. METHODS: Animated visualizations were developed to show outcomes from ixekizumab clinical trials and a Bayesian network meta-analysis of 11 approved biologics. The visualizations simultaneously highlighted both aggregate scores and the individual progression of patients over the course of treatment. RESULTS: The animations provided key messages and information from the complex data in efficient and scientific ways that were also visually pleasing and simple to understand. The animations highlighted (1) rapid reduction in disease severity from baseline; (2) sustained efficacy of ixekizumab in the treatment of skin and nail psoriasis; (3) side-by-side comparisons of treatment efficacy and clinical improvement across trials; (4) simultaneous visual presentation of individual results with summary response over time; and (5) indirect comparison of relative treatment effects with other biologics based on Bayesian network meta-analysis. CONCLUSION: The rapid and sustained efficacy of ixekizumab in the treatment of psoriasis was demonstrated using multiple dynamic visualizations with different clinical endpoints. Animated visualizations provided a simpler and more comprehensive understanding of complex data than conventional static figures.

Effect of Ixekizumab on Patient Reported Outcomes and Quality of Life in Patients With Moderate-to-Severe Plaque Psoriasis: 5-Year Results from the UNCOVER-1 and -2 Studies.

OBJECTIVE: We describe patient-reported outcomes and quality of life through 5 years of treatment in patients with moderate-to-severe plaque psoriasis in the UNCOVER-1 and -2 studies. METHODS: This analysis included patients who were randomized to ixekizumab every 2 weeks then received ixekizumab every 4 weeks during the maintenance period, and who achieved static physician global assessment (0,1) at week 12, completed week 60, and entered the long-term extension period (weeks 60–264). Outcomes measures included responses in itch numeric rating scale (NRS), skin pain visual analog scale (VAS), and dermatology life quality index (DLQI) (0,1), and mean change from baseline in short form health survey (SF-36) mental (MCS) and physical component summaries (PCS), psoriasis skin appearance bothersomeness (PSAB), and work productivity activity impairment (WPAI). RESULTS: At week 264 in UNCOVER-1 and -2, the observed itch NRS ≥4 responses were 82.4% and 93.1%, respectively, the itch NRS=0 responses were 51.7% and 58.5%, respectively, the skin pain VAS=0 responses were 59.3% and 63.1%, respectively, and the DLQI (0,1) responses were 75.0% and 88.1%, respectively. The observed mean changes from baseline at week 264 in UNCOVER-1 and UNCOVER-2 were 3.4 and 6.5, respectively, for SF-36 MCS, 4.4 and 4.8, respectively, for SF-36 PCS, and -21.3 and -22.0, respectively, for PSAB. WPAI psoriasis item scores improved from baseline in both UNCOVER-1 and -2. CONCLUSION: Ixekizumab provided clinically meaningful and sustained improvements in itch, skin pain, DLQI, PSAB, SF-36 PCS, SF-36 MCS, and WPAI through 5 years of treatment in patients with moderate-to-severe plaque psoriasis. J Drugs Dermatol. 20(4):394-401. doi:10.36849/JDD.5821Visit the JDD Psoriasis Resource Center for more.

Long-term efficacy and safety of ixekizumab: A 5-year analysis of the UNCOVER-3 randomized controlled trial.

OBJECTIVE: To report the efficacy and safety of the approved ixekizumab (IXE) dose over 5 years from UNCOVER-3 (NCT01646177). METHODS: Patients (N = 1346) were randomized 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or every 4 weeks after an initial dose of IXE 160 mg, respectively. At week 12, patients entered the long-term extension period with dosing of IXE every 4 weeks and could escalate to every 2 weeks after week 60. Efficacy was reported for the IXE every 2 weeks/every 4 weeks group of the intent-to-treat population. Safety was reported for patients who received at least 1 dose of IXE every 2 or every 4 weeks. RESULTS: Using modified nonresponder imputation, 78.8%/67.1%/46.2% of patients receiving the approved dose of IXE every 2 weeks/every 4 weeks (n = 385) achieved ≥75%, ≥90%, or 100% improvement from baseline in the Psoriasis Area and Severity Index, respectively, at week 264; static Physician's Global Assessment score of 0/1 and 0 responses were 69.2% and 45.3%, respectively. Infections were the most observed treatment-emergent adverse event (72.7% of patients). LIMITATIONS: Lack of comparison treatment group after week 12. CONCLUSION: IXE demonstrates sustained efficacy and consistent safety through 264 weeks in patients using the approved dose.

Epidemiology of psoriasis in hard-to-treat body locations: data from the Danish skin cohort.

BACKGROUND: Having psoriasis in hard-to-treat areas, i.e. the scalp, face, palms, soles, nails, and genitals, respectively, can impair patients' quality of life. We investigated the prevalence of hard-to-treat body locations of psoriasis, and described patients' clinical and demographic characteristics, and quality of life impacts in a population-based cohort. METHODS: We performed a cross-sectional study using a total of 4016 adults (≥18 years) with psoriasis from the Danish Skin Cohort. Groups were compared to patients without involvement of hard-to-treat areas. RESULTS: The most frequently affected hard-to-treat area was the scalp (43.0%), followed by the face (29.9%), nails (24.5%), soles (15.6%), genitals (14.1%), and palms (13.7%), respectively. Higher prevalence was generally seen with increasing psoriasis severity. Among all patients 64.8, 42.4, and 21.9% of patients had involvement of ≥1, ≥2, or ≥ 3 hard-to-treat areas. Those with involvement of certain hard-to-treat areas such as hands, feet, and genitals had clinically relevant DLQI impairments. Having involvement of one hard-to-treat area was significantly associated with other hard-to-treat areas affected even after adjusting for age, sex, and psoriasis severity. CONCLUSION: Psoriasis commonly affects hard-to-treat locations, even in patients with mild disease. For some of these areas, patient-reported disease burden, e.g. as measured by DLQI, is impaired.

Injection Site Reactions in the Federal Adverse Event Reporting System (FAERS) Post-Marketing Database Vary Among Biologics Approved to Treat Moderate-To-Severe Psoriasis.

INTRODUCTION: Biologics used to treat moderate-to-severe plaque psoriasis may cause injection site reactions (ISRs) characterized by erythema, edema, itch, and sometimes pain. The Federal Adverse Event Reporting System (FAERS) is a repository of spontaneous post-marketing reports of adverse events (AEs) that are reported to the US Food and Drug Administration (FDA). Our objective was to perform a pharmacovigilance analysis of FAERS reports of ISRs associated with the use of subcutaneously administered biologic products approved to treat moderate-to-severe plaque psoriasis. METHODS: The products included in our assessment were adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab. Reports from the date of US approval for each biologic as treatment for plaque psoriasis through 2 years were included using the search term "injection site." RESULTS: The results show that the FAERS database contained reports of ISRs for all of the included biologics during the 2 years following FDA approval. The most common reports on ISRs were on pain, irritation, and erythema for adalimumab; reaction, pain, and erythema for etanercept; erythema, pain, and reaction for ixekizumab; bruising, pain, hemorrhage for secukinumab; and pain, induration, and swelling for ustekinumab. FAERS does not include data on total patient exposure; therefore, ISR rates could not be calculated. CONCLUSIONS: Specific ISRs varied among the biologic therapies assessed. The findings presented could be helpful when patients consider switching therapies due to ISRs. FUNDING: Eli Lilly and Company.

Rapid Response of Biologic Treatments of Moderate-to-Severe Plaque Psoriasis: A Comprehensive Investigation Using Bayesian and Frequentist Network Meta-analyses.

INTRODUCTION: Rapid improvement of psoriasis is valued by patients and should be considered to be an important factor in treatment selection. We investigated Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) response rates within the first 12 weeks of treatment to compare the rapid response of 11 biologic therapies for moderate-to-severe psoriasis using Bayesian and Frequentist network meta-analyses (NMA). METHODS: A systematic literature review was conducted to identify phase 3, double-blind, randomized, controlled trials for adult patients with moderate-to-severe psoriasis treated with interleukin (IL)-17 (brodalumab, ixekizumab, secukinumab), IL-12/-23 (ustekinumab), IL-23 (guselkumab, risankizumab, tildrakizumab), or tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab). Outcome measures extracted from 32 publications were ≥ 75, ≥ 90, or 100% improvement in PASI score (PASI 75, PASI 90, or PASI 100, respectively) at weeks 2, 4, 8, and 12 and DLQI    (0,1), where score (0,1) indicates no effect on patient's life, at week 12. Bayesian NMA (BNMA) used fixed-treatment effect and random-baseline effect, normal independent models. Frequentist NMA (fNMA) was conducted as sensitivity analyses to test the robustness of the findings. RESULTS: Based on BNMA and fNMA, brodalumab and ixekizumab showed the most rapid treatment effects on PASI 75 at weeks 2, 4, and 8 and on PASI 90 and PASI 100 at weeks 2, 4, 8, and 12; ixekizumab overlapped with risankizumab on PASI 75 at week 12. Brodalumab, ixekizumab, and secukinumab yielded higher DLQI (0,1) gains at week 12 compared to all of the other biologics studied. Additional measures of quality of life were not assessed in this report. CONCLUSIONS: Ixekizumab and brodalumab provide the most rapid response and earliest clinical benefit at week 2 among all of the biologics studied, including other biologic treatments such as secukinumab, ustekinumab, guselkumab, adalimumab, and etanercept. BNMA and fNMA results showed similar relative effect estimates and treatment rankings. FUNDING: Eli Lilly and Company.

Evaluation of sPGA × BSA as an Outcome Measure and Treatment Target for Clinical Practice.

Clinical outcome measures are becoming more important in psoriasis treatment. Reliable and standardized measures of severity feasible for clinical practice are needed. Our objective was to investigate body surface area (BSA) and the product of BSA and static Physician Global Assessment (sPGA) (ie, BSA × sPGA) as potential proxy measures for PASI scores. Data were pooled from three multicenter, randomized, double-blind, placebo-controlled, phase 3 trials of ixekizumab in patients with moderate to severe psoriasis (UNCOVER-1, -2, -3; N = 3,866). Assessments included the Psoriasis Area and Severity Index (PASI), BSA, and BSA × sPGA. Rank correlations between BSA × sPGA and PASI were stronger than between BSA and PASI (baseline, r = 0.759 vs. r = 0.707; week 12, r = 0.959 vs. r = 0.924). Week 12 concordance rates with PASI responses were as follows: for 75% reduction in PASI: BSA, 86.2%; BSA × sPGA, 93.8%; for 90% reduction in PASI: BSA, 86.9%; BSA × sPGA, 88.2%. The 75% reduction in PASI positive and negative predictive values were higher for BSA × sPGA versus BSA; for 90% reduction in PASI, positive predictive value was lower and negative predictive value was higher for BSA × sPGA versus BSA. Receiver operating characteristic curve analyses identified the most accurate percentage changes in BSA and BSA × sPGA as 66% and 83% for a 75% reduction in PASI cutoff and 84% and 94% for a 90% reduction in PASI, respectively. These results suggest that BSA and BSA × sPGA are viable tools for use as a PASI proxy by real-world practitioners and may be appropriate measurements for use in clinical practice for treat-to-target strategies.

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.

The Static Physician's Global Assessment of Genitalia: A Clinical Outcome Measure for the Severity of Genital Psoriasis.

Introduction: Genital psoriasis is a common but frequently overlooked manifestation of psoriasis with a considerable impact on patients' quality of life. Currently no validated clinical trial outcome measures exist to assess genital psoriasis severity that meet regulatory agency requirements. Methods: This study describes the development of the static Physician's Global Assessment of Genitalia (sPGA-G) scale, a clinical outcome measure for the assessment of genital psoriasis severity that accounts for the erythematous clinical presentation of genital psoriasis. The reliability of the sPGA-G was evaluated using scores collected from clinician assessments of photographs of genital psoriasis cases. Scores were collected from 10 academic and clinical experts in genital psoriasis and 95 clinician assessors who participated in either in-person (n=28) or online (n=67) sPGA-G training modules. Results: The sPGA-G had a high inter-rater reliability (IRR, measured by Kendall's W) for expert raters (W=0.856, P less than 0.0001), in-person assessors (W=0.822, P less than 0.0001), and online assessors (W=0.678, P less than 0.0001). IRR was also high for all clinical assessors combined, (W=0.714, P less than 0.0001). Discussion: This study demonstrates that the sPGA-G is an intuitive and reliable clinical outcome measure that specifically measures the severity of genital psoriasis. J Drugs Dermatol. 2017;16(8):793-799.

Does Teriparatide Improve Femoral Neck Fracture Healing: Results From A Randomized Placebo-controlled Trial.

BACKGROUND: There is a medical need for therapies that improve hip fracture healing. Teriparatide (Forteo(®)/ Forsteo(®), recombinant human parathyroid hormone) is a bone anabolic drug that is approved for treatment of osteoporosis and glucocorticoid-induced osteoporosis in men and postmenopausal women at high fracture risk. Preclinical and preliminary clinical data also suggest that teriparatide may enhance bone healing. QUESTIONS/PURPOSES: We wished to test the hypotheses that treatment with teriparatide versus placebo would improve femoral neck fracture healing after internal fixation as measured by (1) frequency of revision surgery, (2) radiographic fracture healing, and (3) other outcomes including pain control, gait speed, and safety. METHODS: We initiated two separate, but identically designed, clinical trials to meet FDA requirements to provide substantial evidence to support approval of a new indication. The two prospective, randomized double-blind, placebo-controlled Phase III studies were designed to evaluate the effect of subcutaneous teriparatide (20 µg/day) for 6 months versus placebo on fracture healing at 24 months. The trials were conducted concurrently with a planned enrollment of 1220 patients per trial. However, enrollment was stopped owing to very slow patient accrual, and an a priori decision was made to pool the results of those studies for statistical analyses before study completion; pooling was specified in both protocols. Randomization was stratified by fixation (sliding hip screw or multiple cancellous screws) and fracture type (displaced or nondisplaced). An independent Central Adjudication Committee reviewed revision surgical procedures and radiographs. A total of 159 patients were randomized in the two trials (81 placebo, 78 teriparatide). The combined program had very low power to detect the originally expected treatment effect but had approximately 80% power to detect a larger difference of 12% between treatment groups for risk of revision surgery. RESULTS: The proportion of patients undergoing revision surgery at 12 months was 14% (11 of 81) in the placebo group versus 17% (13 of 78) in the teriparatide group. Central Adjudication Committee review excluded two of these patients treated with placebo from the primary analysis. After exclusions, the proportion of patients who did not undergo revision surgery at 12 months (primary endpoint) was not different between the study and placebo groups, at 88% in the placebo group (90% CI, 0.79-0.93) versus 84% in the teriparatide group (90% CI, 0.75-0.90; p = 0.743). There also were no differences between groups in the proportion of patients achieving radiographic fracture healing at 12 months (75% [61 of 81] placebo versus 73% [57 of 78] teriparatide; odds ratio, 0.89; 90% CI, 0.46-1.72; p = 0.692) or in measures of pain control (such as pain during ambulation, 92% [55 of 62] placebo versus 91% [52 of 57] teriparatide; odds ratio, 0.91; 90% CI, 0.25-3.37; p = 0.681). The frequency of patients reporting adverse events was 49% [40 of 81] in the placebo group versus 45% [35 of 78] in the teriparatide group (p = 0.634) during the 6-month treatment period. CONCLUSIONS: The small sample size limited this study's power to detect potential differences, and the results are exploratory. With the patients available, teriparatide did not decrease the risk of revision surgery, improve radiographic signs of fracture healing, or decrease pain compared with the placebo. The adverse event data observed were consistent with the teriparatide safety profile. Functional and health outcome data from the studies may help improve our understanding of patients recovering from femoral neck fractures. Further large controlled studies are required to determine the effect of teriparatide on fracture healing. LEVEL OF EVIDENCE: Level II, prospective study.

An observational study to assess back pain in patients with severe osteoporosis treated with teriparatide versus antiresorptives: An Indian subpopulation analysis.

BACKGROUND: One year, prospective, observational study in an Indian subpopulation to assess back pain in patients with severe osteoporosis treated with teriparatide or antiresorptives in a clinical setting. MATERIALS AND METHODS: One hundred and nineteen teriparatide-naοve Indian men and postmenopausal women (mean age 68.0 years) with previous osteoporotic vertebral fracture participated. Patients were assessed at baseline, 6-and 12-months to evaluate relative risk (RR) of new/worsening back pain using the Back Pain Questionnaire. The incidence of back pain and changes in back pain severity were assessed using the visual analog scale (VAS); Health outcomes were assessed using the euroquol-5 dimensions (EQ-5D) questionnaire. All tests were conducted with a two-sided alpha of 0.05. RESULTS: Of 562 overall patients, 57, 60, and 2 Indian patients received teriparatide, antiresorptive, or teriparatide and antiresorptive, respectively. Baseline disease characteristics were slightly worse for antiresorptive-treated patients, whereas teriparatide-treated patients were older with more comorbidities. At 6-months, the incidence of new/worsening back pain was 5.3% for teriparatide-treated patients versus 4.4% for antiresorptive-treated patients (RR: 1.00, 95% confidence interval: 0.68, 1.48); the incidence of severe back pain was 0% versus 12.5% (P = 0.017); in these treatment groups, respectively. Mean VAS change scores (mean ± standard deviation [SD]) were - 1.9 ± 1.73 versus - 1.4 ± 1.77, and mean EQ-5D change scores were 4.2 ± 27.20 versus 9.9 ± 26.23 at 6-months. At 6 months, more teriparatide-treated patients felt better (89% vs. 61%; P = 0.001) and were at least very satisfied with their treatment (30% vs. 9%; P = 0.011). CONCLUSION: Teriparatide-treated Indian patients had similar new/worsening back pain risk and minimal risk of severe back pain compared with antiresorptive-treated patients at 6-months.

Baseline glucocorticoid dose and bone mineral density response with teriparatide or alendronate therapy in patients with glucocorticoid-induced osteoporosis.

OBJECTIVE: This post-hoc analysis studied the effect of baseline glucocorticoid dose on the 18-month bone mineral density (BMD) response to teriparatide 20 microg/day or alendronate 10 mg/day in 387 patients with glucocorticoid-induced osteoporosis (GIO) from a randomized, double-blind trial. METHODS: Lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were measured at baseline and 18 months. Mean baseline glucocorticoid dose was categorized as low (< or = 5 mg/day), medium (> 5 and < 15 mg/day), or high (> or = 15 mg/day). RESULTS: Baseline LS, FN, and TH BMD were similar between groups, and between glucocorticoid dose categories within each group. LS BMD increases at the low, medium, and high glucocorticoid doses were 8.1%, 6.6%, and 4.6%, respectively, with teriparatide, and 3.6%, 2.8%, and 2.3% with alendronate. Analyzed as a continuous variable, higher glucocorticoid doses had a negative, but non-significant, effect on the percentage increase in LS BMD in both groups. Glucocorticoid dose did not significantly affect FN or TH BMD increases in either group. Across the 3 glucocorticoid dose categories, the overall LS BMD increases were different for both treatments combined (p = 0.033), but the relative differences between the treatment groups were not different (interaction, p = 0.52). CONCLUSION: Teriparatide and alendronate increased LS and hip BMD across a range of baseline glucocorticoid doses. LS BMD increases with teriparatide were greater in the low-dose category than in the high-dose category. Overall LS BMD increases were significantly greater with teriparatide compared with alendronate, which may reflect the respective anabolic and antiresorptive mechanisms of action. Clinical Trial Registry Number: NCT00051558.