Dear Editor
Psoriasis is an immune‐mediated skin disease characterized by an increased inflammatory response mediated by the IL23/IL17 axis. 1 , 2 The latest generation of biologic drugs (i.e., guselkumab, risankziumab, and tildrakizumab) selectively inhibit the p19 subunit of interleukin 23 (IL23), 3 , 4 , 5 , 6 which acts upstream of the IL23/IL17 pathway. The efficacy of these drugs has been confirmed by phase three studies which showed safety profile and remarkable effects in terms of Psoriasis Area Severity Index (PASI) 90 and 75, achieved by more than 75% of patients treated with guselkumab/Risankizumab and more than 60% of patients treated with Tildrakizumab. 4 , 5 , 6 While these molecules demonstrated superiority over older tumour necrosis factor (TNF) alpha inhibitors, efficacy over anti‐IL17 was not always evident. 4 , 6 , 7 IL23 blockade doesn't always work for psoriasis and can lose efficacy after initial benefit. Herein, we report the experience of our clinic on patients who switched from anti‐IL23 to IL17. In the last year, out of 769 patients with moderate‐ severe psoriasis followed at the Dermatology Clinic of the Turin University Hospital, seven patients switched to an IL17 inhibitor after treatment failure with IL23 inhibitor (Table 1). In all seven cases, the switch was made directly without wash‐out and intercurrent therapy. The mean age was 48.7 years (ds 6.1), with a mean onset of psoriasis at 25 (ds 2.7). The population was mainly female (five out of seven patients). The mean BMI was 25, none of the patients was obese or diabetic, 2 patients had an increased cardiovascular risk. Six patients suffered from psoriasis vulgaris, one patient presented a pustular form. Three patients had joint involvement. No significant differences were found with the general population in our clinic (Table 1). Six patients discontinued guselkumab and one patient discontinued risankizumab. Four out of seven patients had previously used more than one biologic agent. The mean follow‐up of treatment with anti‐IL23 was 7 months, primary ineffectiveness was the first cause of discontinuation (five out of seven cases), followed by secondary ineffectiveness. One case of perimalleolar edema was reported in risankizumab‐treated patients. Four patients subsequently started brodalumab and 3 ixekizumab, one patient performed a rechallenge with ixekizumab. Currently, all patients are continuing these treatments. The initial mean PASI at the switch was 8.3 (ds 2.3) and after 16 weeks dropped to 1.1 (ds 2.0), with five out of seven patients achieving PASI100; in the following weeks the response was maintained with mean PASI at weeks 24, 40 and 52 of 1.4, 1.4, and 1.6, respectively. No side effects were reported.
TABLE 1.
Patients' characteristics and outcomes, and comparison with the general psoriatic population at our clinic in the time analyzed
| No. of patients | Age | Sex | BMI | Age of onset | Type of Psoriasis | PSA | Bilogic in course | Previous biological therapy | PASI at baseline | PASI 16w | PASI 90 16w | PASI100W | PASI a 28settimane | PASI90 28 W | PASI 10028 W | PASI 40 W | PASI90 40 W | PASI 10040 W | PASI 52 W | PASI90 52 W | PASI 10052 W | Follow up (months) | Cause of IL23inhibitors suspension | Obesity | Cardiovascular disease | Diabetes Mellitus |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 62 | 1 | 27 | 46 | Vulgar | No | Brodalumab | Ixekizumab, risankizumab | 8 | 0 | Yes | Yes | 0 | Yes | Yes | 2 | No | No | 5 | Prior inefficacy, adverseevent | No | Yes | No | |||
| 2 | 66 | 0 | 25 | 4 | Vulgar | Yes | Brodalumab | Ixekizumab, guselkumab | 8 | 0 | No | No | 0 | Yes | Yes | 2 | No | No | 0 | Yes | Yes | 5 | Second inefficacy | No | No | No |
| 3 | 51 | 1 | 28 | 26 | Vulgar | No | Ixekizumab | Secukinumab, ixekizumab, guslkumab | 6 | 0 | Yes | Yes | 0 | Yes | Yes | 0 | Yes | Yes | 0 | Yes | Yes | 6 | Prior inefficacy, | No | No | No |
| 4 | 34 | 0 | 20 | 18 | Vulgar, inverse | No | Brodalumab | Guselkumab | 14 | 5 | No | No | 5 | No | No | 5 | No | No | 5 | No | No | 12 | Second inefficacy | No | No | No |
| 5 | 22 | 0 | 29 | 16 | Vulgar | No | Brodalumab | Guselkumab | 7 | 0 | Yes | Yes | 0 | Yes | Yes | 0 | Yes | Yes | 6 | Prior inefficacy | No | No | No | |||
| 6 | 45 | 0 | 21 | 11 | Vulgar | Yes | Ixekizumab | Guselkumab | 5 | 0 | Yes | Yes | 0 | Yes | Yes | 1 | No | No | 10 | Prior inefficacy | No | No | No | |||
| 7 | 61 | 0 | 25 | 55 | Pustolar | Yes | Ixekizumab | Ustekinumab, guselkumab | 10 | 3 | No | No | 3 | No | No | 0 | Yes | Yes | 7 | Prior inefficacy | No | Yes | No | |||
| Switched patients (7) | General population (783) | p‐value | ||||||||||||||||||||||||
| Sex (F/M) | 71.4% | 35.5% | 0.104 | |||||||||||||||||||||||
| Age (mean) | 48.7 | 52.2 | 0.886 | |||||||||||||||||||||||
| Age of onset (mean) | 25.1 | 34.3 | 0.947 | |||||||||||||||||||||||
| PSA (yes/no) | 42.8% | 28.7% | 0.475 | |||||||||||||||||||||||
| BMI (mean) | 25 | 27 | 0.225 | |||||||||||||||||||||||
| Obesity (yes/no) | 0% | 23.8% | 1 | |||||||||||||||||||||||
| Cardiovascular disease (yes/no) | 28.6% | 44% | 0.475 | |||||||||||||||||||||||
| Diabetes Mellitus (yes/no) | 0% | 12.7% | 1 | |||||||||||||||||||||||
Abbreviation: PASI, Psoriasis severity index.
Switches from one generation of biologics to the previous one has been previously described and few cases from secukinumab to ustekinumab or adalimumab, with subsequent good responses, have been reported. 1 , 8 In most of our patients, the reason for switching was an initial failure of therapy, with subsequent initiation of IL17 receptor inhibitor with brodalumab and to a lesser extent ixekizumab. A rapid response was obtained in all patients. The biological reason for these observations remains to be investigated, primarily due to the complex biology of psoriasis. Probably a more selective inhibition of the cytokine cascade in some patients allows a better response or allows evasion of hypothetical antibodies inactivating the anti‐IL23. In the case of rechallenge, the intercurrent use of anti‐IL23 could guarantee a modification of the cytokine milieu and the patient's immune response, allowing a resumption of the efficacy of IL17 inhibitor after initial treatment. Our evidence and our hypotheses must be confirmed by larger sample sizes studies. Nevertheless, the switch to an earlier monoclonal antibody may be an adequate therapeutic option in psoriatic patients who fail an anti‐IL23.
AUTHOR CONTRIBUTIONS
Luca Mastorino and Gabriele Roccuzzo made the data analysis, write and review the manuscript. Pietro Quaglino and Simone Ribero made the supervision, review and approved the manuscript. Paolo Dapavo and Niccolò Siliquini made the supervision and approved the manuscript. Gianluca Avallone and Marco Rubatto made the visualization, read and approved the manuscript.
FUNDING INFORMATION
None.
CONFLICT OF INTEREST
The author declares that there is no conflict of interest.
DECLARATION
All the patients signed informed written consent.
ACKNOWLEDGMENT
Open Access Funding provided by Universita degli Studi di Torino within the CRUI‐CARE Agreement.
Luca Mastorino and Gabriele Roccuzzo share first authorship.
DATA AVAILABILITY STATEMENT
Data available upon reasonable request.
REFERENCES
- 1. Chiricozzi A, Conti A, Burlando M, et al. Switching from Secukinumab to Ustekinumab in Psoriasis Patients: Results from a Multicenter Experience. Dermatology. 2019;235(3):213‐218. doi: 10.1159/000497274 [DOI] [PubMed] [Google Scholar]
- 2. Mastorino L, Roccuzzo G, Dapavo P, et al. Patients with psoriasis resistant to multiple biologic therapies: characteristics and definition of a difficult‐to‐treat population. Br J Dermatol. 2022. [ahead of print]. doi: 10.1111/bjd.21048 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Dapavo P, Siliquini N, Mastorino L, et al. Efficacy, safety, and drug survival of IL‐23, IL‐17, and TNF‐alpha inhibitors for psoriasis treatment: a retrospective study. J Dermatolog Treat. 2021;33(4);1‐6. doi: 10.1080/09546634.2021.1961998 [DOI] [PubMed] [Google Scholar]
- 4. Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti‐interleukin‐23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double‐blinded, placebo‐ and active comparator‐controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405‐417. doi: 10.1016/j.jaad.2016.11.041 [DOI] [PubMed] [Google Scholar]
- 5. Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate‐to‐severe plaque psoriasis (UltIMMa‐1 and UltIMMa‐2): results from two double‐blind, randomised, placebo‐controlled and ustekinumab‐controlled phase 3 trials. Lancet. 2018;392(10148):650‐661. doi: 10.1016/S0140-6736(18)31713-6 [DOI] [PubMed] [Google Scholar]
- 6. Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;390(10091):276‐288. doi: 10.1016/S0140-6736(17)31279-5 [DOI] [PubMed] [Google Scholar]
- 7. Blauvelt A, Papp K, Gottlieb A, et al. A head‐to‐head comparison of ixekizumab vs. guselkumab in patients with moderate‐to‐severe plaque psoriasis: 12‐week efficacy, safety and speed of response from a randomized, double‐blinded trial. Br J Dermatol. 2020;182(6):1348‐1358. doi: 10.1111/bjd.18851 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Damiani G, Conic RRZ, de Vita V, et al. When IL‐17 inhibitors fail: Real‐life evidence to switch from secukinumab to adalimumab or ustekinumab. Dermatol Ther. 2019;32(2):e12793. doi: 10.1111/dth.12793 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data available upon reasonable request.