This 197-patient study is one of the largest registry studies conducted to date to examine the efficacy and safety of real-world patients receiving IL-23p19 inhibitors, as well as the impact of prior biological exposure on these parameters. The rate of off-label dosage changes was relatively low, i.e. 1.0% in this study compared to 14.1% for the IL-12/23 inhibitor ustekinumab , which had previously been reported in this registry.seven. All anti-IL-23 inhibitors combined, the observed response rates/LOCF at 3 months with PASI 100 were 29.9%/25.4%; for PASI 90, 47.3%/40.1%; and for PASI 75, 63.5%/53.8%. After 12 months, the PASI 100 values reached 49.4%/38.6%; for PASI 90, 63.2%/53.3%; and for PASI 75, 78.2%/69.0%.
The treatment efficacy in terms of PASI reduction category for guselkumab observed in this study was in the lower range or slightly lower than that reported in clinical trials. Three months after treatment initiation, PASI 75 response was 60.2% (vs. 69.8–91.2%), PASI 90 response was 39.8% (vs. 69.0–73.3% ) and the PASI 100 response was 27.8% (as compared to 27.0-37.4%). Fifty-two weeks after treatment initiation, PASI 75 response was 76.7% (vs. 77.8–87.8%), PASI 90 response was 61.7% (vs. 76, 3–84.0%) and the PASI 100 response was 46.7% (vs. 46.7–58.0%) (Fig. 2, Table 5)20,21,22. In general, these response rates are also within range (or slightly lower) than those recently published from real-world Italian patient cohorts.23,24,25.
Treatment results for risankizumab were also in the lower range or slightly lower than clinical trial results. PASI 75 responses at 12 weeks were 74.5% (vs. 91.0–94.5%), PASI 90 responses were 63.9% (vs. 72.0–74.8%) and PASI 100 responses were 42.6% (vs. 32.7–40.0%). Fifty-two weeks after treatment initiation, PASI 75 response was 84.0% (vs. 96.4%), PASI 90 response was 72.0% (vs. 80.6–92, 7) and the PASI 100 response was 60.0% (vs. 41.8–60.0%) (Fig. 2, Table 5)1.26. Similar data regarding treatment efficacy have been obtained in recently published real-world studies.27.28.
However, it should be noted that the efficacy endpoints in most of these clinical trials (of guselkumab and risankizumab) were measured 16 weeks after treatment initiation, whereas this study analyzed efficacy of treatment 12 weeks after the start of treatment.1,21,22,26,29. Additionally, the rate of biologic non-naïve patients in this study was higher than in clinical trials, 57.5% and 47.3% biologic non-naïve patients for guselkumab and risankizumab, respectively. , compared to a range of 17.5–29.0% in the guselkumab trials and 29.0–39.0% in the risankizumab trials (Table 1)1,20,21,22,26.
Patients receiving tildrakizumab had treatment responses that were mostly well within the range of outcomes cited in clinical trials, with a PASI 75 response at 12 weeks in this study of 50% (vs. 41.2 to 64 .0%), a PASI 90 response of 50.0% (vs. 35.0-73.2%) and a PASI 100 response of 8.3% (vs. 14.0-34.4%) . Meanwhile, twenty-six weeks after the start of treatment, a PASI 75 response of 57.2% was recorded (vs. 73.0–80.0%), a PASI 90 response of 42.9% ( versus 52.0–56.0%) and a PASI 100 response of 28.6% (vs. 23.0–24.0%) (Fig. 2, Table 5)30,31,32. However, better real-word response rates have recently been reported in Italian patient cohorts.25.33. Similar to the rates for non-biologic-naïve patients observed in clinical trials of guselkumab and risankizumab, the rates observed for non-biologic-naïve patients receiving tildrakizumab were 26.7% in this study; thus, this rate was slightly higher than the rate observed in its clinical trials (13.0 to 23.0%) (Table 1). However, PASI 34. In particular, 52 patients (26.4%) included in this study started treatment with PASI ≤ 3 (Table 1). After excluding these patients, the results of the LOCF analysis reveal that 80.0% of patients achieved PASI ≤ 3 at 12 months, which is considered to meet the therapeutic treatment goal (Table 5)35. On the other hand, this result indicates that 1 in 5 patients did not show an entirely satisfactory response to the treatment (Table 5). With respect to PASI reduction, 23.4% did not achieve a PASI 75 response and 13.1% (or one in eight patients) remained below a PASI 50 level of improvement or their skin manifestations even worsened (Table 5). Notably, similar PASI reduction rates were observed when patients starting with PASI ≤ 3 were not excluded from the analysis (Table 5).
Analysis of treatment outcomes of the entire cohort with respect to prior biologic exposure revealed higher rates of PASI 50, PASI 75, PASI 90, and PASI 100 responses in biologic treatment naïve patients compared to patients not naïve to biological treatment at 3, 6 and 12 months after the start of treatment (Table S2). These results are consistent with clinical trial results and early real-world data, which show better treatment outcome in biologic-naïve patients or patients directly randomized to the IL-23p19 arm instead of the biologic crossover arm.9,23,26,30,32,36,37. However, it seems that the class of biological previously administered does not influence the efficacy of IL-23p19 inhibitors (Table 4). Of note, patients previously treated with IL-17 inhibitors had the highest PASI values at baseline among non-biological treatment-naïve patients (Table 4). This may indicate a more difficult-to-treat patient cohort, as many more patients had already received more than one prior biologic treatment in the IL-17 group (65.1%) compared to those in the TNF-alpha group (35 .0%) and IL12/23 Groups (25.0%) (Table 1). This finding is consistent with another analysis of Austrian registry data, which found that patients treated with IL-17 inhibitors were significantly more often non-biological treatment-naïve patients.seven. The results indicate that switching from IL-17 inhibitors to IL-23 inhibitors could be a promising therapeutic alternative in the event of treatment failure with IL-17 inhibitors. Nevertheless, biologic-naïve patients showed significantly higher PASI improvement for all time points measured, despite higher skin burden at the start of treatment (Table 2). However, after correcting for prior biologic drug exposure, no major differences in PASI improvement could be detected in PASI at any time point in biologic treatment-naïve or non-biologic patients in this regard. regarding the drug administered, with the exception of PASI at 12 months in non-biological patients. – naïve patients. (Table 3). These results indicate that all IL-23 inhibitors are promising drugs for the subsequent treatment of non-biologic-naïve patients.
Overall, the rate of adverse events (11.67%) observed in this study is much lower than that reported in clinical trials, as well as in real-world patients (Table 6)20,24,28,29,31. Adverse event rates found in this study were also similar to previously published rates between biologic-naïve and non-naïve patients (Table S3)38.
Aside from the retrospective registry design, limitations of this study include that only a small number of patients received tildrakizumab, which limits the validity of the results reported for this drug. Additionally, more patients than usual may have deviated from regular administration of prescribed medication due to the ongoing pandemic for several reasons (e.g. being quarantined, waiting for vaccination, or worrying about developing a more severe course of COVID-19 during/due to taking immunomodulating drugs).