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About the Author


Parbeer Grewal, MD

Dr. Grewal is the medical director at Rejuvenation Dermatology and Aesthetics in downtown Edmonton and is also an associate clinical professor at the University of Alberta in the division of dermatology. He obtained his undergraduate degree at the University of Alberta and also completed both his Doctor of Medicine (MD) degree and dermatology training at the University of Alberta too. He is also a consulting physician for the University of Alberta Hospital, the Royal Alexandra Hospital, the Grey Nuns Hospital and the Misericordia Hospital. Dr. Grewal has participated in over 60 clinical research trials for a multitude of dermatology conditions and medications. Dr. Grewal also serves on multiple national and international scientific advisory boards, is a distinguished peer reviewer for medical journals and has published both journal articles and book chapters in dermatology.

Special Supplement, Canadian Dermatology Today, August, 2021

Tildrakizumab in patients with metabolic syndrome: A novel approach

Tildrakizumab is a high-affinity, humanized, IgG1 k antibody targeting interleukin 23 p19 to treat patients with chronic plaque psoriasis.1 The Food and Drug Administration (FDA) approved ILUMYATM (tildrakizumab-asmn) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy in March 2018 and it has also been approved in Australia, Japan and numerous European countries. The approved recommended dosage of ILUMYATM in the United States is a subcutaneous injection of 100 mg at Weeks 0, 4, and every 12 weeks thereafter.2 In Canada, tildrakizumab has not yet been approved for the treatment of moderate-to-severe plaque psoriasis.

This article presents a fictitious case study of a patient who may be a good candidate for tildrakizumab and provides an underlying rationale for the choice of tildrakizumab in this clinical scenario.

A 39-year-old male presents to the office for a repeat visit for severe psoriasis. He has had psoriasis for 6 years and has failed topical therapy, and oral systemic agents. His past medical history is significant for obesity, hypertension, and impaired fasting glucose tolerance. His current medications include a multi-vitamin and an angiotensin receptor blocker. His family history is significant for obesity, hypertension, diabetes, and myocardial infarction. He travels quite frequently for work and, therefore is not able to commit to a phototherapy schedule. In choosing a biologic therapy, the new class of anti-IL23p19 agents have distinct clinical advantages that may be beneficial for this type of patient. 

Injection Frequency and Injection Site Reactions

Anti-IL23p19 agents, such as risankizumab and tildrakizumab, and anti-IL12/23 agents, like ustekinumab, have the longest interval between injections. All are dosed at week 0, week 4 and then every 12 weeks thereafter.2-4 As well, anti-IL23p19 agents have a lower incidence of injection site reactions (<0.5%) in comparison to agents like ixekizumab (7.7 to 10% from UNCOVER-3) and adalimumab5,6 


Anti-IL23p19 agents have high rates of clinical efficacy and durability. In reSURFACE 1 and reSURFACE 2, with tildrakizumab 100mg dosing, up to 64% of patients achieved a PASI 75 score, 35% achieved a PASI 90 score, 14% achieved a PASI 100 score and 59% achieved a PGA score of 0 or 1 at week 12 after 2 doses of drug.7 Over time, the durability of responses to tildrakizumab are very stable with most patients maintaining their responses and others achieving an even higher level of psoriasis clearance. At 148 weeks, using non-responder imputation, patients on tildrakizumab 100 mg dosing achieved a PASI 75 rate of 72.6%, a PASI 90 rate of 53.8% and a PASI 100 rate of 28.9%. These results are comparable to other anti-IL23p19 and anti-IL17 agents.5 

Cardiometabolic Effects

Patients with psoriasis have a higher degree of obesity (OR = 1.8), hypertension (OR = 1.58), diabetes (OR = 1.76) and dyslipidemia (OR = 1.04 to 5.55).8 Severe psoriasis by itself can also confer a 6.2% increased absolute risk of developing a major adverse cardiovascular event (MACE) compared to the general population.9 All of these factors combined, greatly increase the risk of cardiac and cerebrovascular events leading to significantly more morbidity and mortality in psoriasis patients.

The concern with using biologic therapy in this group of patients, is that metabolic syndrome itself can lower the patient’s response to these biologic agents resulting in lower PASI responses and more long-term drug failure.10 However, the efficacy of tildrakizumab was the same, irrespective of patients having pre-existent metabolic syndrome. In general, patients with metabolic syndrome had higher body weight, BMI, cardiovascular disease and diabetes mellitus, compared with patients without metabolic syndrome in tildrakizumab studies. The efficacy of both tildrakizumab 100- and 200-mg doses was maintained over 148 weeks of the study without evidence of reduced drug survival in patients with metabolic syndrome.11-14 

Recent studies using biologic therapy have sought to elucidate the relationship between the reduction of systemic inflammation and by extension the mitigation of cardiometabolic events associated with untreated psoriasis. A recent study in JAMA Cardiology, that followed psoriasis patients from 2013-2019, analyzed 134 patients (82 on biologic therapy and 52 with skin-directed therapy). The investigators measured coronary inflammation via computed tomography angiography (CTA) by assessing fat attenuation index (FAI). The results demonstrated that patients on biologic therapy had greater improvements in PASI scores and only they had reduction of high sensitivity CRP scores (HS-CRP) as evaluated by FAI.15 Another recent publication by Elbanawi et al in 2019 followed 121 patients who were all biologic naïve at baseline (89 biologic, 32 topical/light) and at 1 year of follow up, found a 5% reduction in coronary plaque build-up in the biologic group.16

A recent paper by Mehta (2019) showed clinically relevant numerical decreases in fasting glucose, triglycerides, and systolic blood pressure over time in patients treated with tildrakizumab.17 Cautious extrapolation would suggest that using tildrakizumab might be efficacious regardless of underlying metabolic syndrome status. Lebwohl et al (2020) came to a similar conclusion after a post-hoc analysis of reSURFACE 1 and reSURFACE 2 noting that the efficacy, safety and drug survival of tildrakizumab was comparable in psoriasis irrespective of underlying metabolic syndrome.18

A recent study presented at the 28th European Academy of Dermatology and Venereology Congress (EADV) illustrated the benefits of tildrakizumab for patients with psoriasis with comorbid metabolic syndrome. Over 3 years, 75% to 100% skin clearance was reached and sustained equally in patients with and without metabolic syndrome. Metabolic syndrome is determined by elevated blood pressure, body mass index/obesity, triglycerides, glucose, and low HDL cholesterol levels.19

In reSURFACE 1, 69% and 71% of patients with and without metabolic syndrome achieved PASI 75, respectively; 42% and 51% of patients with and without metabolic syndrome achieved PASI 90, respectively; and 27% and 23% of patients with and without metabolic syndrome achieved PASI 100, respectively at week 12. In reSURFACE 2, 73% and 79% of patients achieved PASI 75; 57% and 60% achieved PASI 90; and 34% and 32% achieved PASI 100, respectively at week 12.5

In our fictitious patient case, there would be confidence in using an agent that works in spite of metabolic syndrome and works to perhaps lower risk factors at the same time.


Over 148 weeks of therapy, the rate of treatment emergent adverse events for tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept were 35.2, 37.2, 148.6 and 148.6 events per 100 patient years. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, bronchitis, and sinusitis. Overall, there were low rates of severe infections, malignancies, and MACE for treatment with tildrakizumab over a 148-week period. All adverse events were comparable to placebo and there were no new or unexpected adverse events concerning candida infections, exacerbation of inflammatory bowel disease, suicidal ideation or behavior or any other treatment emergent adverse event.5


In conclusion, tildrakizumab is an effective, durable, and safe therapy with a convenient injection frequency. There is robust data to suggest that tildrakizumab works well in those with metabolic syndrome and may lower the risk of metabolic disease itself leading to improved patient outcomes. Based on these known facts, our patient may greatly benefit from tildrakizumab therapy. 


1. Galluzzo, Marco, et al. “Tildrakizumab for treating psoriasis.” Expert opinion on biological therapy 17.5 (2017): 645-657.

2. FDA product monograph tildrakizumab;

3. FDA product monograph ustekinumab;

4. FDA product monography Risankizumab;

5. Reich, K., et al. “Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (re SURFACE 1 and re SURFACE 2) through 148 weeks.” British Journal of Dermatology 182.3 (2020): 605-617.

6. Gordon KB et al. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med 2016; 375:345-356.

7. Reich, Kristian, et al. “Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials.” The Lancet 390.10091 (2017): 276-288.

8. Puig, Lluís. “Cardiometabolic comorbidities in psoriasis and psoriatic arthritis.” International journal of molecular sciences 19.1 (2018): 58.

9. Mehta, Nehal N., et al. “Attributable risk estimate of severe psoriasis on major cardiovascular events.” The American journal of medicine 124.8 (2011): 775-e1.

10. Jacobi, Arnd, Stephan J. Rustenbach, and Matthias Augustin. “Comorbidity as a predictor for drug survival of biologic therapy in patients with psoriasis.” International journal of dermatology 55.3 (2016): 296-302.

11. Gottlieb et al. “Effect of metabolic syndrome on efficacy and safety in patients with psoriasis treated with etanercept or tildrakizumab: Post hoc analysis of 2 phase 3 clinical studies (reSURFACE 1 and reSURFACE 2)”; Presented at the 28th European Academy of Dermatology and Venerology (EADV) Congress, October 9–13, 2019, Madrid, Spain

12. Gottlieb et al. “Tildrakizumab Efficacy by Metabolic Syndrome Status in Psoriasis: Post Hoc Analysis of 3-Year Data from the Phase 3 reSURFACE 2 Study”; Presented at the 28th European Academy of Dermatology and Venerology (EADV) Congress, October 9–13, 2019, Madrid, Spain

13. Lebwohl et al. “ Relationship of Serum Glucose to Efficacy and Safety of Tildrakizumab Treatment for Psoriasis in Patients With and Without Metabolic Syndrome from reSURFACE 1 and reSURFACE 2”; Presented at the 28th European Academy of Dermatology and Venerology (EADV) Congress, October 9–13, 2019, Madrid, Spain

14. Lebwohl et al. “Tildrakizumab Efficacy by Metabolic Syndrome Status in Psoriasis: Post Hoc Analysis of 3-Year Data from the Phase 3 reSURFACE 1 Study”; Presented at the 28th European Academy of Dermatology and Venerology (EADV) Congress, October 9–13, 2019, Madrid, Spain

15. Dufour, Justine, et al. “Recent Advances in Evaluating Impact of Biologic Therapy for Moderate-Severe Psoriasis on Cardiovascular Events and Atherosclerotic Plaque Formation.” Journal of Cutaneous Medicine and Surgery 24.2 (2020): 209-210.

16. Elnabawi, Youssef A., et al. “Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study.” Cardiovascular research 115.4 (2019): 721-728.

17. Menter MA, Mehta NN, Lebwohl MG, et al. “The Effect of Tildrakizumab on Cardiometabolic Risk Factors in Psoriasis by Metabolic Syndrome Status: Post Hoc Analysis of Two Phase 3 Trials (ReSURFACE 1 and ReSURFACE 2)”. J Drugs Dermatol. 2020;19(8):703-708. doi:10.36849/JDD.2020.5337

18. Lebwohl MG, Leonardi CL, Mehta NN, et al. 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). J Am Acad Dermatol. 2020;82(2):519-522.

19.  Gottlieb, Alice B., and Frank Dann. “Comorbidities in patients with psoriasis.” The American journal of medicine 122.12 (2009): 1150-e1.