Safety
Tildrakizumab treatment was generally well tolerated. TEAEs reported through week 28 are summarized in Table 2. TEAEs occurred in 31 (56.4%) patients; the most frequently reported were skin and subcutaneous tissue disorders (20.0%), infections and infestations (14.5%), musculoskeletal and connective tissue disorders (10.9%), and gastrointestinal disorders (10.9%). No TEAEs of tuberculosis, opportunistic infections, or inflammatory bowel disease occurred in this study. Serious TEAEs occurred in 3 (5.5%) patients (COVID-19 infection, cerebrovascular accident, immunoglobulin A nephropathy; n = 1 each). No TEAEs were considered related to tildrakizumab treatment. One AE of transitional cell carcinoma (1.8%) before week 28 led to discontinuation after week 28.
DISCUSSION
This week 28 interim analysis of data from a 64-week, Phase 4 trial provides insights into the effectiveness and safety of tildrakizumab treatment in community practice patients with moderate-to-severe plaque psoriasis. Significant clinical improvement from baseline was observed at week 28 based on PASI response thresholds, with low disease activity based on absolute PASI score, BSA, sPGA, and BSA x sPGA. No new safety concerns were identified.
Both clinical improvement and disease activity are important indicators of treatment effectiveness. Improvement is desirable to patients, especially those with a large disease burden at baseline; however, a patient with high baseline disease severity who experiences 90% improvement may still have clinically significant disease after treatment. Conversely, a patient with moderate disease severity at baseline may have very acceptable low disease severity after treatment despite not achieving response thresholds such as the PASI 90. The results of our study emphasize that real-world tildrakizumab treatment is effective in terms of both clinical improvement and disease activity.
There is a knowledge gap regarding the real-world effectiveness of biologic therapies for plaque psoriasis compared with the efficacy and safety observed in clinical trials. Randomized clinical trials enroll select patient populations with stringent inclusion and exclusion criteria. In contrast, real-world studies provide valuable insights from a patient-centric perspective and allow physicians and the greater medical community to see the effects of treatments from a far more generalizable context.12 The results of this real-world analysis are consistent with those of the Phase 3 reSURFACE 1 and reSURFACE 2 clinical trials. In reSURFACE 1 and reSURFACE 2, 77% and 73%, respectively, of patients treated with tildrakizumab 100 mg for 28 weeks achieved PASI 75 response; 49% and 55%, respectively, achieved PASI 90 response.7 The mean (SD) pooled PASI scores at baseline, week 12, and week 28 were 20.2 (7.7), 5.7 (7.0), and 4.6 (6.6), respectively. In addition, the overall frequencies of TEAEs were generally similar between the Phase 3 trials and the present study.7
AEs reported in the current analysis are consistent with the safety profile of tildrakizumab in clinical practice, with common TEAEs including nasopharyngitis and upper respiratory tract infection.5
LIMITATIONS
Limitations of this interim analysis include the lack of a comparator study arm, a relatively short duration of follow-up, and a limited number of patients
CONCLUSION
This interim analysis provides information on the effectiveness and safety of tildrakizumab treatment beyond clinical trials, demonstrating the impact of treatment on clinical outcomes in patients with moderate-to-severe plaque psoriasis in the real-world setting. The full 1-year results are expected to provide further insight into the safety and effectiveness of tildrakizumab in clinical practice.
Data Availability Statement: Data and other documents will be made available after publication, with no end date, to anyone who submits a reasonable request to the study sponsor.
DISCLOSURES
JH has been a speaker, advisor, and consultant for AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Boehringer Ingelheim, and Novartis; an advisor for Galderma, Mayne, Regeneron, and Sanofi; an advisor and consultant for Ortho Dermatologics; and a speaker and advisor for Sun Pharma, Incyte, LEO Pharma, and Beiersdorf. JGV reports nothing to disclose. BS is an employee of Sun Pharmaceutical Industries, Inc. NB is an advisor, consultant, and investigator for AbbVie, Almirall, Arcutis, Beiersdorf, Biofrontera, Bristol Myers Squibb, Boehringer Ingelheim, Cara, Dermavant, Eli Lilly, EPI Health, Ferndale, Galderma, Genentech, InCyte, ISDIN, Johnson & Johnson, LaRoche-Posay, LEO Pharma, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and Verrica.
Funding: The study was funded by Sun Pharma. Medical writing and editorial support were provided by Nitish Chaudhari, PhD, of AlphaBioCom, LLC, and funded by Sun Pharma.
ACKNOWLEDGMENT
The authors express gratitude and appreciation to the trial patients and staff who participated in these trials. We thank Drs. Tina Bhutani, John Koo, and Stephen J. Rozzo for their contributions to the study. The authors acknowledge medical writing and editorial support provided by Nitish Chaudhari PhD, of AlphaBioCom, LLC, and funded by Sun Pharma.
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AUTHOR CORRESPONDENCE
Jayme Heim MSN FNP-BC heim.jayme@gmail.com
