Tildrakizumab efficacy and safety are not altered by metabolic syndrome status in patients with psoriasis: Post hoc analysis of 2 phase 3 randomized controlled studies (reSURFACE 1 and reSURFACE 2)
Authors: Mark G. Lebwohl, Craig L. Leonardi, Nehal N. Mehta, Alice B. Gottlieb, Alan M. Mendelsohn, Jeff Parno, Stephen J. Rozzo, Alan Menter
Journal: Journal of the American Academy of Dermatology (2019)

To the Editor: This post hoc analysis evaluated tildrakizumab efficacy, durability of response, and safety in patients with moderate to severe chronic psoriasis with vs without metabolic syndrome (MetS) using pooled data from 2 phase 3, double-blind, randomized, placebo-controlled studies, reSURFACE 1 (A Study to Evaluate the Efficacy and Safety of Subcutaneous MK-3222, Followed by an Optional Long-Term Safety Extension Study, in Participants With Moderate-to-Severe Chronic Plaque Psoriasis [MK-3222-010]; NCT01722331) and reSURFACE 2 (A Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab [SCH 900222/MK-3222] in Participants With Moderate-to-Severe Chronic Plaque Psoriasis Followed by a Long-term Extension Study [MK-3222-011]; NCT01729754). Methods were previously described1Reich K. Papp K.A. Blauvelt A. et al.Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials.Lancet. 2017; 390: 276-288Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar and are summarized in the Supplemental material (available at https://data.mendeley.com/datasets/fj89yr8c9s/1). Patients with vs without MetS had higher prevalence of pre-existing cardiovascular disease and diabetes and higher median baseline weight and body mass index (Supplemental Table I; available at https://data.mendeley.com/datasets/fj89yr8c9s/1). Six patients (4.1%) with MetS (n = 5 tildrakizumab 100 mg; n = 1 tildrakizumab 200 mg) and 25 patients (4.5%) without MetS (n = 12 tildrakizumab 100 mg; n = 13 tildrakizumab 200 mg) did not complete the study. Percentages of patients with ≥75% improvement on the Psoriasis Area and Severity Index (PASI 75 responders) at weeks 12 and 52 were comparable between patients with and without MetS for both tildrakizumab doses (Fig 1). Percentages of PASI 90 (Supplemental Fig 1, A; available at https://data.mendeley.com/datasets/fj89yr8c9s/1) and PASI 100 (data not shown) responders through week 52 were similar regardless of MetS status for both tildrakizumab doses. Tildrakizumab efficacy through week 52 was maintained comparably in patients with and without MetS. Reductions in mean PASI from baseline were similar regardless of MetS status for both tildrakizumab doses (Supplemental Fig 1, B; available at https://data.mendeley.com/datasets/fj89yr8c9s/1). Percentages of patients with ≥1 serious adverse event (AE) and those with ≥1 serious infection were similar in patients with and without MetS (Table I). The most common serious AEs for patients with vs without MetS were gastrointestinal and cardiac disorders after tildrakizumab 100 mg and injury/procedural complications and nervous system disorders after tildrakizumab 200 mg. Fatal AEs occurred in 2 patients with MetS (both tildrakizumab 100 mg) and 2 patients without MetS (1 per tildrakizumab dose).Table IPatients with treatment-emergent adverse events and serious adverse events by metabolic syndrome (MetS) status through week 64∗Data are presented as number (%) by Medical Dictionary for Regulatory Activities system organ class. Patients may have had ≥1 serious adverse events.Adverse eventsTildrakizumab 100 mgTildrakizumab 200 mgWithout MetS (n = 290)With MetS (n = 79)Without MetS (n = 263)With MetS (n = 67)Total treatment-emergent adverse events222 (76.6)67 (84.8)212 (80.6)57 (85.1)Total serious adverse events21 (7.2)8 (10.1)20 (7.6)7 (10.4) Cardiac02 (2.5)†1 event of coronary artery stenosis and 1 event of myocardial infarction in patients with cardiovascular history.01 (1.5)‡1 patient had atrial fibrillation and mitral valve incompetence. Ear and labyrinth1 (0.3)000 Endocrine1 (0.3)000 Eye0001 (1.5)§1 event of cataract. Gastrointestinal3 (1.0)2 (2.5)‖1 event of hemorrhoids thrombosed and pancreatitis.2 (0.8)0 General/administration site conditions01 (1.3)¶1 event of noncardiac chest pain.2 (0.8)0 Hepatobiliary1 (0.3)01 (0.4)0 Infections and infestations3 (1.0)1 (1.3)#1 event of erysipelas.3 (1.1)1 (1.5)1 event of diverticulitis. Injury, poisoning, procedural complications3 (1.0)02 (0.8)2 (3.0) 2 events of tendon rupture. Musculoskeletal, connective tissue1 (0.3)1 (1.3)1 event of cervical spinal stenosis.3 (1.1)0 NeoplasmsBenign, malignant, and unspecified (including cysts and polyps).4 (1.4)03 (1.1)1 (1.5)1 event of squamous cell carcinoma of skin. Nervous system1 (0.3)002 (3.0)1 event of radiculopathy and sciatica. Psychiatric2 (0.7)000 Reproductive system and breast001 (0.4)0∗ Data are presented as number (%) by Medical Dictionary for Regulatory Activities system organ class. Patients may have had ≥1 serious adverse events.† 1 event of coronary artery stenosis and 1 event of myocardial infarction in patients with cardiovascular history.‡ 1 patient had atrial fibrillation and mitral valve incompetence.§ 1 event of cataract.‖ 1 event of hemorrhoids thrombosed and pancreatitis.¶ 1 event of noncardiac chest pain.# 1 event of erysipelas.∗∗ 1 event of diverticulitis.†† 2 events of tendon rupture.‡‡ 1 event of cervical spinal stenosis.§§ Benign, malignant, and unspecified (including cysts and polyps).‖‖ 1 event of squamous cell carcinoma of skin.¶¶ 1 event of radiculopathy and sciatica. Open table in a new tab Infection was the most commonly reported treatment-emergent AE. Incidence was similar in patients with and without MetS receiving tildrakizumab 100 mg and numerically higher in patients with and without MetS receiving tildrakizumab 200 mg. The incidence of cardiovascular events did not vary by MetS status, and there were no reports of diabetes worsening after treatment (Supplemental Table II; available at https://data.mendeley.com/datasets/fj89yr8c9s/1). Weight increases through week 28 were limited (∼1 kg on average) in patients with and without MetS across both tildrakizumab doses. Exposure-adjusted rates of tier 1 treatment-emergent AEs were comparable across doses regardless of MetS status (Supplemental Table III; available at https://data.mendeley.com/datasets/fj89yr8c9s/1). These post hoc analyses were not powered for statistical analyses based on MetS status, and populations were not matched for smoking history and other potential cofactors. Although abdominal obesity is more highly correlated with MetS risk factors relative to body mass index,2National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.Circulation. 2002; 106: 3143-3421Crossref PubMed Scopus (11286) Google Scholar the latter was used because abdominal obesity data were not collected. Sample sizes for patients with MetS were relatively small. Further evaluation of the effect of weight only on treatment efficacy and safety was not feasible because only 25 patients with a body mass index of <30 kg/m2 met ≥3 criteria for MetS. Despite limitations, these results suggest efficacy, safety, and drug survival of tildrakizumab are comparable in patients with psoriasis regardless of MetS status. The authors thank the patients who took part in this study. Editorial assistance was provided by Georgia Bakirtzi, PhD, of JK Associates, Inc, part of the Fishawack Group of Companies; and Judith M. Phillips, DVM, PhD, of AlphaBioCom, LLC; and was funded by Sun Pharmaceutical Industries, Inc.