Evaluation of sPGA x 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 x 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 x sPGA. Rank correlations between BSA x 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 x sPGA, 93.8%; for 90% reduction in PASI: BSA, 86.9%; BSA x sPGA, 88.2%. The 75% reduction in PASI positive and negative predictive values were higher for BSA x sPGA versus BSA; for 90% reduction in PASI, positive predictive value was lower and negative predictive value was higher for BSA x sPGA versus BSA. Receiver operating characteristic curve analyses identified the most accurate percentage changes in BSA and BSA x 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 x 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

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 mu g/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 ( 5 and = 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 nonsignificant, 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. (First Release Nov 15 2009; J Rheumatol 2010;37:141-8; doi:10.3899/jrheum.090411

Baseline Glucocorticoid Dose and Bone Mineral Density Response with Teriparatide or Alendronate Therapy in Patients with Glucocorticoid-induced Osteoporosis

ABSTRACT. Objective. This post-hoc analysis studied the effect of baseline glucocorticoid dose on the 18-month bone mineral density (BMD) response to teriparatide 20 µg/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 (≤ 5 mg/day), medium (> 5 and < 15 mg/day), or high (≥ 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 nonsignificant, 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). Glucocorticoids effectively treat inflammatory conditions but are associated with an array of side effects 1 , including secondary osteoporosis 2 . The pathophysiology of glucocorticoid-induced osteoporosis (GIO) involves multiple mechanistic pathways, including early increases in bone resorption along with decreased bone formation, and alterations in bone microarchitecture 3 . Daily or cumulative oral glucocorticoid doses are related to decreased bone mass and the occurrence of fractures 2,4 . However, patients treated with oral glucocorticoids experience fractures at a higher bone mineral density (BMD) than patients with postmenopausal osteoporosis 5 , and the fracture risk is greater than predicted by decreased bone mass alone 6 , suggesting that glucocorticoids can also negatively affect bone quality 1,2,5 . Other mechanisms of bone fragility, such as osteocyte apoptosis and reduced repair of local defects, may contribute to the increased fracture risk observed in patients treated with chronic glucocorticoids 7 . Current guidelines for management of GIO include assessment of patients for osteoporosis risk factors prior to initiating glucocorticoid therapy, concomitant use of calcium and vitamin D supplements, and for prolonged treatment of the underlying disease, minimizing the glucocorticoid dose and/or tapering the glucocorticoid dose in low disease Conclusion

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)

Abstract 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)

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

<p><b>Background:</b> Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17 A.</p> <p><b>Objective:</b> Examine the efficacy of ixekizumab in clearing psoriasis within different body regions.</p> <p><b>Methods:</b> 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, <i>N</i> = 792; UNCOVER-2, -3, <i>N</i> = 361), 50 mg ETN twice weekly (<i>N</i> = 740), or 80 mg ixekizumab every 2 (IXE Q2W; <i>N</i> = 1169; <i>N</i> = 736) or 4 weeks (IXE Q4W; <i>N</i> = 1165; <i>N</i> = 733) after a 160-mg starting dose.</p> <p><b>Results:</b> 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 <i>p</i> < .001 vs. PBO). Mean regional PASI improvements at Week 12 were ≥84.2% for ixekizumab versus ≤70.9% for ETN in all regions (<i>p <</i> .001). Scaling and thickness reduced faster than erythema.</p> <p><b>Conclusions:</b> 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.</p