both trials.7 Patients receiving tildrakizumab who successfully completed the reSURFACE 1 or reSURFACE 2 base study with at least a PASI 50 response were eligible to enroll in an optional extension study and receive the same dose of tildrakizumab for an additional 4 years. In pooled data analyses from reSURFACE 1 and reSURFACE 2, long-term treatment with tildrakizumab in patients who achieved a PASI 75 response at week 28 was associated with sustained disease control and a favorable safety profile for up to 5 years of total treatment.9
Although the efficacy and safety of tildrakizumab are well established in the clinical trial setting, little published real-world evidence is available from clinical practice settings. This manuscript reports the effectiveness of tildrakizumab in terms of clinical improvement and residual disease activity, as well as safety of tildrakizumab, from the week 28 interim analysis of a 64-week Phase 4 study in real-world practice.
MATERIALS AND METHODS
Study Design and Population
This Phase 4, open-label, real-world study was conducted at 2 sites in the United States, initiated in July 2019, and registered at www.ClinicalTrials.gov (record #NCT03718299). Eligible patients were immunocompetent, aged greater than or equal to 18 years, had moderate-to-severe plaque psoriasis that was diagnosed at least 6 months prior to study entry, had greater than or equal to 3% of their total body surface area (BSA) affected by psoriasis, and were candidates for phototherapy or systemic therapy. Patients were excluded from the study if they had erythrodermic psoriasis; only pustular, guttate, or inverse psoriasis; or evidence of skin conditions other than psoriasis that would interfere with study-related evaluations of psoriasis. Patients with prior or concomitant treatment with any biological agent other than tildrakizumab within 1 week prior to baseline, any new investigational drug within 12 weeks prior to baseline, or new treatment for psoriasis not used consistently prior to screening were also excluded. The study was conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The study protocol was reviewed and approved by a central Institutional Review Board, and all patients were required to provide written informed consent prior to study initiation.
Treatment and Assessments
All patients received tildrakizumab 100 mg by subcutaneous injection at week 0, week 4, and every 12 weeks thereafter through week 52. The interim analysis was performed after all patients had the opportunity to complete treatment up to week 28. The investigator assessed patients' PASI scores at baseline and weeks 4, 16, and 28. The percentage of BSA affected and the static PGA (sPGA) were assessed by the investigator at baseline, every 4 weeks up to week 16, and at week 28. For the percentage of BSA affected, investigators could use the estimate that 1% BSA is equivalent to the area of the patient's closed hand. To determine sPGA, first, the psoriasis plaque attributes of induration, erythema, and scaling were rated on individual 6-point scales (0 = no evidence to 5 = severe), with each attribute averaged over the patient's entire body. Final sPGA was then obtained based on another 6-point scale (0 = clear, except for residual discoloration, to 5 = severe, lesions have individual induration, erythema, and scaling scores of at least 5).10
Safety was evaluated from AEs, which were reported spontaneously by patients or elicited by investigators during questioning and examination of a patient at any time during the study. AE data collected included date of onset, location (within/not within the affected region), severity (mild, moderate, severe), and relationship to treatment (not related, unlikely, possibly, probably, definitely).
Outcomes
The primary endpoint of the study, improvement in quality of life as measured by change from baseline in the total Psychological General Well-Being Index score, is reported elsewhere.11 In this interim analysis, clinical improvement during tildrakizumab treatment through week 28 was evaluated from improvement from baseline in PASI score and the proportions of patients achieving 75%/90%/100% improvement from baseline PASI score (PASI 75/90/100 responses, respectively). Disease activity was evaluated from the percentage of BSA affected, sPGA, and sPGA x BSA over time.
Safety was assessed based on the incidence and severity of treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs through week 28.
Statistical Analysis
Sample Size
A sample size of 60 patients screened was selected to provide adequate estimates; no formal sample size calculations were performed. Following screening, 55 patients were enrolled in the study.
Effectiveness Analyses
Effectiveness was analyzed in the intention-to-treat (ITT) population, which consisted of all enrolled patients assigned to receive study medication. Descriptive statistics were calculated for the absolute values and percentage changes from baseline in PASI score, BSA, sPGA, and sPGA x BSA; the PASI 75/90/100 response rates were also summarized with descriptive statistics. Changes from baseline were analyzed using Student's t-test. Missing data were not imputed.
Safety Analyses
Safety analyses included all enrolled patients who received at least 1 dose of study treatment (safety population). The TEAEs were classified by Medical Dictionary for Regulatory Activities
