but was concerned about side effects and frequent laboratory monitoring; oral apremilast 30 mg twice daily was initiated while anticipating lab work and following up with her primary care physician. She experienced mild improvement but selfdiscontinued apremilast therapy after four months because of severe daily nausea.
The skin lesions continued for over a year despite subsequent treatment with topical corticosteroids under occlusion and narrowband UVB phototherapy twice weekly. The patient continued to experience severe pain when walking due to fissures and thickened skin on her feet. Because of ongoing debilitating symptoms, including worsening depression due to her condition, an injectable biologic was planned as the next option. Despite her unintentional weight loss, appropriate laboratory investigations and cancer screenings relevant to cachexia remained negative. Her primary care physician provided approval for proposed therapy with tildrakizumab.
The patient started tildrakizumab 100 mg subcutaneous injection at week 0, week 4, and every 12 weeks thereafter. At baseline, she had affected body surface area (BSA) of 20% and a Physical Global Assessment (PGA) score of 4. Significant improvement was noted after 30 days, with reduction of BSA to 1% and PGA to 1. Three months later, she continued to show substantial improvement, with 100% clearance of the lesions on her extremities (Figure 2). The patient was then diagnosed with lung cancer, and tildrakizumab therapy was paused while she initiated chemotherapy. At last contact, the patient was treated solely with topical medication for psoriasis for 6 months and reported only "a few flareups.â€
The skin lesions continued for over a year despite subsequent treatment with topical corticosteroids under occlusion and narrowband UVB phototherapy twice weekly. The patient continued to experience severe pain when walking due to fissures and thickened skin on her feet. Because of ongoing debilitating symptoms, including worsening depression due to her condition, an injectable biologic was planned as the next option. Despite her unintentional weight loss, appropriate laboratory investigations and cancer screenings relevant to cachexia remained negative. Her primary care physician provided approval for proposed therapy with tildrakizumab.
The patient started tildrakizumab 100 mg subcutaneous injection at week 0, week 4, and every 12 weeks thereafter. At baseline, she had affected body surface area (BSA) of 20% and a Physical Global Assessment (PGA) score of 4. Significant improvement was noted after 30 days, with reduction of BSA to 1% and PGA to 1. Three months later, she continued to show substantial improvement, with 100% clearance of the lesions on her extremities (Figure 2). The patient was then diagnosed with lung cancer, and tildrakizumab therapy was paused while she initiated chemotherapy. At last contact, the patient was treated solely with topical medication for psoriasis for 6 months and reported only "a few flareups.â€
DISCUSSION
Our patient, whose diagnosis of PPP was supported by clinical manifestations and biopsy findings, was successfully treated with tildrakizumab and achieved complete clearance. Clinical improvement was maintained for several months after withdrawal of systemic treatment due to chemotherapy.
Tildrakizumab was selected in part because of our concern about undiagnosed malignancy; oncologists consulted were more comfortable with selective IL-23 blockade due to limited immunosuppression. Furthermore, tildrakizumab is not contraindicated in patients with cancer, although such patients were excluded from phase 3 trials.11 Other considerations included need for rapid onset and minimal risk for side effects due to the patient’s deteriorating quality of life. Despite disease duration of 20 years at baseline, tildrakizumab treatment at the approved dose resulted in near-complete resolution of PPP. The reasons for the patient’s poor response to prior conventional therapies for PPP are unclear, but severe cases of psoriasis can benefit from systemic therapy with immunomodulatory biologics. Treatment with the IL-23p19 inhibitor tildrakizumab significantly improves both cutaneous symptoms and quality of life in patients with moderate-to-severe plaque psoriasis.11-13 Targeting the IL-23/Th17 axis with selective IL-23p19 antagonists may be an effective and safe therapeutic option for chronic PPP; promising results were reported for treatment of PPP with guselkumab, another selective IL-23p19 inhibitor, in phase 2 and phase 3 randomized clinical trials conducted in Japan.14,15
Tildrakizumab is generally well tolerated, with advantages of simple and infrequent dosing and mild adverse effects.13 Although the IL-23p19 inhibitors share a similar safety profile, tildrakizumab is administered every 12 weeks during maintenance dosing, compared with every 8 weeks for guselkumab.4 Therefore, tildrakizumab may be more convenient for clinical management.
Tildrakizumab was selected in part because of our concern about undiagnosed malignancy; oncologists consulted were more comfortable with selective IL-23 blockade due to limited immunosuppression. Furthermore, tildrakizumab is not contraindicated in patients with cancer, although such patients were excluded from phase 3 trials.11 Other considerations included need for rapid onset and minimal risk for side effects due to the patient’s deteriorating quality of life. Despite disease duration of 20 years at baseline, tildrakizumab treatment at the approved dose resulted in near-complete resolution of PPP. The reasons for the patient’s poor response to prior conventional therapies for PPP are unclear, but severe cases of psoriasis can benefit from systemic therapy with immunomodulatory biologics. Treatment with the IL-23p19 inhibitor tildrakizumab significantly improves both cutaneous symptoms and quality of life in patients with moderate-to-severe plaque psoriasis.11-13 Targeting the IL-23/Th17 axis with selective IL-23p19 antagonists may be an effective and safe therapeutic option for chronic PPP; promising results were reported for treatment of PPP with guselkumab, another selective IL-23p19 inhibitor, in phase 2 and phase 3 randomized clinical trials conducted in Japan.14,15
Tildrakizumab is generally well tolerated, with advantages of simple and infrequent dosing and mild adverse effects.13 Although the IL-23p19 inhibitors share a similar safety profile, tildrakizumab is administered every 12 weeks during maintenance dosing, compared with every 8 weeks for guselkumab.4 Therefore, tildrakizumab may be more convenient for clinical management.
CONCLUSION
Our patient with long-standing PPP was successfully treated
with tildrakizumab, with complete resolution of lesions and no
notable adverse effects. Further study of biologic use in patients
with less common forms of psoriasis such as PPP can improve
our understanding of the entire spectrum of therapeutic
potential.
DISCLOSURES
Dr. Del Campo reports no potential conflicts of interest to
disclose.
ACKNOWLEDGMENT
We thank the patient for providing permission for this case
report. Medical writing and editorial support were provided
by Judy Phillips, DVM, PhD, CMPP, of AlphaBioCom, LLC, and
funded by Sun Pharmaceutical Industries, Inc.
REFERENCES
1. Freitas E, Rodrigues MA, Torres T. Diagnosis, screening and treatment of patients with palmoplantar pustulosis (PPP): A review of current practices and recommendations. Clin Cosmet Investig Dermatol. 2020;13:561-578.
2. Rendon A, Sch kel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475.
2. Rendon A, Sch kel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475.
