Commentary
In patients with moderate-to-severe plaque psoriasis, biologic therapy has become a mainstay of treatment. Of recent agents, tildrakizumab is a monoclonal antibody targeting interleukin-23 (IL-23) that has been approved for treatment of moderate-to-severe plaque psoriasis in several countries worldwide [1]. While phase III clinical trials and subsequent open-label extension studies have evaluated its efficacy and safety, real-world evidence involving patients from routine clinical practice is limited [1, 2]. While our group previously reported real-world drug survival outcomes of up to 3 years with tildrakizumab, this subset analysis focuses on its effectiveness and safety [1].
We included adult patients with plaque psoriasis that received tildrakizumab from 14 centers in Canada, Spain, Italy, Portugal, and Switzerland. Patients were initiated on tildrakizumab as per standard dosing. The study design has been previously described [1]. The primary effectiveness outcome measured was absolute Psoriasis Area and Severity Index (PASI) score. A modified Non-Responder Imputation (mNRI) analysis was applied for response-related discontinuation. Safety was measured via adverse events (AEs). The study was conducted using anonymized and deidentified data in adherence with ethical standards with institutional research board (IRB) approval at the academic institutions involved.
This analysis identified 517 patients. The mean age was 50.1 (SD ± 15.8) years with 61.5% (318/517) being male (Table 1); 74.1% (383/517) and 35% (181/517) patients had previously utilized conventional systemic therapy/phototherapy or biologics, respectively. We identified 426, 315, and 148 patients who continued tildrakizumab at year 1, 2, and 3, respectively.
Table 1.
Baseline demographic and clinical characteristics for adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab
| Demographic and clinical characteristics | Value |
|---|---|
| Sex, n (%) | |
| Male | 318 (61.5) |
| Female | 199 (38.5) |
| Baseline age (years), mean ± SD | 50.1 ± 15.8 |
| Disease duration (years), mean ± SD | 16.8 ± 12.5 |
| Baseline BMI, mean ± SD | 26.3 ± 4.3 |
| Comorbidities, n (%) | |
| Hypertension | 137 (26.5) |
| Dyslipidemia | 126 (24.4) |
| Obesity | 70 (13.5) |
| PsA | 42 (8.1) |
| Latent tuberculosis | 50 (9.7) |
| Hepatitis B | 13 (2.5) |
| Hepatitis C | 12 (2.3) |
| Inflammatory bowel disease | 4 (0.8) |
| Smoking status, n (%) | |
| Smoker | 133 (25.7) |
| Previous treatments, n (%) | |
| Phototherapy | 146 (28.2) |
| Systemic non-biologic therapy | 383 (74.1) |
| Methotrexate† | 201 (39.1) |
| Cyclosporine† | 150 (29) |
| Retinoids† | 96 (18.6) |
| Apremilast† | 11 (2.1) |
| Systemic biologic therapy | 181 (35) |
| Adalimumab‡ | 113 (21.9) |
| Secukinumab‡ | 37 (7.2) |
| Ustekinumab‡ | 37 (7.2) |
| Etanercept‡ | 36 (6.7) |
| Ixekizumab‡ | 24 (4.6) |
| Risankizumab‡ | 16 (3.1) |
| Guselkumab‡ | 11 (2.1) |
| Infliximab§ | 10 (1.9) |
| Brodalumab‡ | 8 (1.6) |
| Certolizumab‡ | 2 (0.4) |
| Bimekizumab‡ | 1 (0.2) |
| Number of prior biologic treatments | |
| 1 | 117 (22.6) |
| 2 | 40 (7.7) |
| ≥ 3 | 24 (4.6) |
| Baseline PASI, mean ± SD | 11.5 ± 6 |
BMI body mass index; n number of patients meeting criteria; PASI psoriasis area and severity index; PsA psoriatic arthritis; SD standard deviation
†Oral route ‡subcutaneous route §intravenous route
At 1 year (n = 426), 87.6% (373/426), 69.3% (295/426), and 50% (213/426) achieved absolute PASI scores ≤ 3, ≤ 1, and 0, respectively. At 2 years (n = 315), 80.3% (253/315), 63.2% (199/315), and 51.1% (161/315) achieved absolute PASI scores ≤ 3, ≤ 1, and 0, respectively. Finally, at 3 years (n = 148), 78.4% (116/148), 61.5% (91/148), and 48% (71/148) reached absolute PASI scores ≤ 3, ≤ 1, and 0, respectively (Table 2). Achievement of PASI ≤ 3 (at years 1 and 3) was found to be significantly higher in biologic-naïve versus biologic-experienced patients (Supplementary Table 1, Supplementary Table 2). Response rates were not impacted by obesity (BMI ≥ 30) status (Supplementary Table 2). During treatment, 3.1% (16/517) underwent dose escalation of tildrakizumab (from 100 to 200 mg), and 1.4% (7/517) used concomitant systemic therapies.
Table 2.
Effectiveness and safety outcomes for tildrakizumab treatment in adult patients with moderate-to-severe plaque psoriasis
| Effectiveness and safety outcomes | Value |
|---|---|
| Effectiveness outcomes at 1 year | n/N (%) |
| PASI ≤ 3 | 373/426 (87.6) |
| PASI ≤ 1 | 295/426 (69.3) |
| PASI 0 | 213/426 (50) |
| Effectiveness outcomes at 2 years | |
| PASI ≤ 3 | 253/315 (80.3) |
| PASI ≤ 1 | 199/315 (63.2) |
| PASI 0 | 161/315 (51.1) |
| Effectiveness outcomes at 3 years | |
| PASI ≤ 3 | 116/148 (78.4) |
| PASI ≤ 1 | 91/148 (61.5) |
| PASI 0 | 71/148 (48) |
| Mean ± SD | |
| PASI after 1 year of treatment | 1.1 ± 2 |
| PASI after 2 years of treatment | 1.2 ± 0.5 |
| PASI after 3 years of treatment | 1.3 ± 2.1 |
| Safety outcomes | n/N (%) |
| Treatment-emergent adverse events of special interest | |
| Infection | 29/517 (5.6) |
| Infection leading to hospitalization | 1/517 (0.2) |
| Injection site reaction | 3/517 (0.6) |
| Malignancy | 2/517 (0.4) |
| Carcinoid tumor | 1/517 (0.2) |
| Follicular lymphoma | 1/517 (0.2) |
| Heart failure | 1/517 (0.2) |
| Hepatic abnormalities | 0/517 (0) |
n number of patients meeting criteria; PASI psoriasis area and severity index; PASI75 75% improvement in psoriasis area and severity index from baseline; SD standard deviation
In this cohort of patients, 10.8% (56/517) experienced treatment-emergent AEs (TEAEs) (Table 2, Supplementary Table 3). Of these, infection was most common (5.6%, 29/517), with 0.2% (1/517) of patients requiring hospitalization. Malignancy was documented in 0.4% (2/517) of patients. Injection site reaction was documented in 0.6% (3/517). Regarding cardiac AEs, one patient (0.2%) received a new diagnosis of heart failure (New York Heart Association Functional Class III) during tildrakizumab treatment. No hepatic abnormalities were observed. Eighty-eight (17%) patients discontinued tildrakizumab with reasons including lack of efficacy (9.5%, 49/517) and AEs (2.3%, 12/517: infection [n = 6]; malignancy [n = 2]; lymphocytosis [n = 1], myalgia [n = 1]; uncontrolled dyslipidemia [n = 1]; alopecia areata [n = 1]). Safety data were further explored in our previously reported drug survival analysis [1].
Our real-world absolute PASI outcomes for tildrakizumab at years 1 and 3 are comparable to NRI outcomes from open-label extension studies (reSURFACE 1 and reSURFACE 2) at weeks 52 and weeks 148 [2]. A similar study from Italy (n = 136) is the longest real-world follow-up of tildrakizumab to date, which demonstrated 84.4% achievement of PASI ≤ 2 [3]. For 3 years, our safety data were consistent with open-label extension studies at the same timepoint, including for TEAEs of special interest [4, 5]. Of note, in our previous analysis of this cohort, we identified a real-world drug survival of 91.3% at 1 year, 85.3% at 2 years, and 82.4% at 3 years for patients, revealing that tildrakizumab is favorably tolerated in the long term and further supporting our effectiveness/safety results [1]. Study limitations include its small sample size, retrospective nature, a lack of available laboratory monitoring data, and a lack of available effectiveness metrics aside from PASI. Overall, our real-world data support the long-term use of tildrakizumab for plaque psoriasis.
Supplementary Information
Below is the link to the electronic supplementary material.
Author Contributions
Tiago Torres and Jensen Yeung contributed to concept and design, data collection, statistical analysis, and drafting of the manuscript. Orhan Yilmaz contributed to data collection. Siddhartha Sood, Ronald Bernard Vender, Vimal H Prajapati, Luis Puig, Matteo Megna, Angelo Valerio Marzano, Paolo Gisondi, Jose Manuel Carrascosa, Esteban Dauden, Mar Llamas-Velasco, Anna Balato, Barbara Guerra Leal, Francesca Prignano, Francesco Bellinato, Gianmarco Silvi. Eugenia Veronica Di Brizzi, Luca Potestio, Carlo Giovanni Carrera, Anna López-Ferrer, Elena Del-Alcazar, Asfandyar Mufti, Lara Valeska Maul, Stefano Piaserico, and Julia Tatjana Maul contributed to data collection and drafting of the manuscript.
Funding
No funding or sponsorship was received for this study or publication of this article.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Conflict of interest
Tiago Torres has been an advisor, consultant, investigator and/or speaker for AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius Kabi, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz, and UCB. Tiago Torres, Luis Puig, Paolo Gisondi, Jose Manuel Carrascosa, and Anna Lopez-Ferrer are members of the editoral board of Dermatology and Therapy. Tiago Torres, Luis Puig, Paolo Gisondi, Jose Manuel Carrascosa, and Anna Lopez-Ferrer were not involved in the selection of peer reviewers for the manuscript or any of the subsequent editorial decisions. Francesca Prignano served as advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Eli-Lilly, Janssen, Novartis, Biogen, Sanofi Genzyme, UCB, and Boehringer-Ingelheim. Esteban Dauden has the following conflict of interests: Advisory Board member, consultant, grants, research support, participation in clinical trials, honorarium for speaking, with the following pharmaceutical companies: Abbvie/Abbott, Almirall, Amgen-Celgene, Johnson & Johnson/Janssen-Cilag, Leo-Pharma, Novartis, Pfizer, MSD-Schering-Plough, Lilly, UCB, Brystol-Myers and Boehringer-Ingelheim. Mar Llamas-Velasco has the following conflict of interests: Advisory Board member, consultant, grants, research support, participation in clinical trials, honorarium for speaking, with the following pharmaceutical companies: Abbvie/Abbott, Almirall, Amgen-Celgene, Boehringer-Ingelheim, Brystol-Myers, Cantabria Labs, Johnson & Johnson/Janssen-Cilag, Leo-Pharma, Kyowa-Kirin, Novartis, Lilly, UCB. Anna Balato has served as speaker and/or has received fees from Abbvie, Almirall, Amgen, BI, BMS, Eli-Lilly, Janssen, Leo-Pharma, Novartis, Sanofi, UCB. Matteo Megna has acted as a speaker or consultant for Almirall, Abbvie, Amgen, Bristol Myers Squibb, Eli Lilly, Leo Pharma, Janssen, Novartis, and UCB. Luis Puig has received consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius-Kabi, Horizon (DSMB), J&J Innovative Medicine, Leo-Pharma, Lilly, Novartis, Pfizer, Samsung-Bioepis, STADA, Sun-Pharma, and UCB. Angelo Valerio Marzano reports consultancy/advisory boards disease-relevant honoraria from AbbVie, Amgen, Boehringer-Ingelheim, Bristol Myers Squibb, Incyte, Leopharma, Novartis, Pfizer, Sanofi, and UCB. Paolo Gisondi has been a consultant and/or speaker for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. Idolazzi served as consultant and/or speaker for AbbVie, Amgen, Biogen, Merck Sharp & Dohme, Eli Lilly, Novartis, Celgene, and Sandoz Girolomoni served as consultant and/or speaker for AbbVie, Abiogen, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol-Meyers Squibb, Celltrion, Eli Lilly, Genzyme, Leo Pharma, Novartis, OM Pharma, Pfizer, Regeneron, Samsung, Sandoz, and UCB. Carlo Giovanni Carrera has served as a board participant or speaker for Abbvie, Lilly, Janssen, Novartis, Celgene, Almirall, and Leopharma. Anna López Ferrer has received payments or honoraria for educational events, support to attend meetings, and participation in advisory boards or consultancies from Abbvie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Johnson and Johnson, Eli Lilly, Leo Pharma, Novartis and UCB. Stefano Piaserico has been a consultant and/or speaker for Abbvie, Almirall, Amgen, Bristol Myers, Janssen, LEO Pharma, Eli Lilly, Merck Sharp Dohme, Novartis, Pfizer, Sandoz, and UCB. Prof. Julia-Tatjana Maul has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Incyte, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, and UCB. Lara Valeska Maul has served as advisor and/or received speaking fees and/or grants and/or participated in clinical trials sponsored by Almirall, Amgen, Bristol-Myers Squibb (BMS), Canfield, Eli Lilly, Incyte, L’ Oreal, Merck Sharp & Dohme (MSD), Novartis, Pierre Fabre, Roche, and Sanofi outside of the submitted work. Ronald Vender has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, Aralez, Arcutis, Astellas, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Centocor, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Innovaderm, Janssen, Kabi-Care, LEO Pharma, Merck, Novartis, Palladin, Pfizer, Regeneron, Sandoz, Sun Pharma, Takeda, UCB, and Viatris-Mylan. Vimal H. Prajapati has been an advisor, consultant, and/or speaker for AbbVie, Actelion, Amgen, Apogee Therapeutics, Aralez, Arcutis, Aspen, Bausch Health, BioJAMP/JAMP Pharma, BioScript Solutions, Boehringer Ingelheim, Bristol Myers Squibb, Canadian Psoriasis Network, Celgene, Celltrion, Cipher, CorEvitas, Eczema Society of Canada, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte, J&J Innovative Medicine, Janssen, Johnson & Johnson, LEO Pharma, Medexus, Novartis, Organon, Paladin, Pediapharm, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Tribute, and UCB; investigator for AbbVie, AnaptysBio, Apogee Therapeutics, Apollo Therapeutics, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, J&J Innovative Medicine, Janssen, LEO Pharma, Nektar Therapeutics, Nimbus Lakshmi, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Reistone, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and Vyne Therapeutics; and received grants from AbbVie, Bausch Health, Janssen, LEO Pharma, Novartis, and Sanofi Genzyme. Jensen Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, Anacor, Arcutis, Astellas, Bausche, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Coherus, Dermira, Forward, Fresenius Kabi, Galderma, Incyte, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and Xenon. Asfandyar Mufti has been a speaker for AbbVie and Janssen. Jose-Manuel Carrascosa has received consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, J&J. Leo-Pharma, Lilly, Novartis, Pfizer, Pfizer, Galderma, Sanofi and UCB. The remaining authors (Siddhartha Sood, Orhan Yilmaz, Jose Manuel Carrascosa, Gianmarco Silvi, Eugenia Veronica Di Brizzi, Barbara Guerra Leal, Elena Del-Alcazar, Francesca Bellinato, Luca Potestio) have no relevant disclosures of interest to declare.
Ethical Approval
The study was conducted using anonymized and deidentified data in adherence with ethical standards with institutional research board (IRB) approval at academic insitutions involved.
Footnotes
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References
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Associated Data
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Supplementary Materials
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.