De Novo Psoriasis Following Belatacept Therapy in Transplant Recipients: Case Series

Belatacept is an immunoglobulin fusion protein that selectively inhibits T-cell activation by blocking CD28 signaling and disrupting CTLA4 (cytotoxic T-lymphocyte associated protein 4) and CD80/CD86 interactions on immune cells. With its favorable cardiovascular and renal profile, belatacept is increasingly utilized as an alternative agent to prevent organ rejection in kidney transplant recipients (KTRs) [1]. While generally well-tolerated, belatacept has been associated with psoriasis, with two cases of psoriasis reactivation and one case of de novo psoriasis reported in the current literature [2, 3]. Cicora et al. reported two transplant patients who developed psoriasis reactivation after initiating belatacept [2]. Another case involved a post-renal transplant patient on mycophenolic acid for maintenance therapy, who developed de novo psoriatic plaques after starting belatacept. The patient's psoriasis resolved completely several weeks after discontinuing belatacept, suggesting a potential causal relationship [3]. Our transplant service has observed six patients on belatacept who developed de novo psoriasis, suggesting this may be underreported and under-recognized. This case series defines the patient characteristics and treatment approaches in patients with transplant-associated psoriasis. Using the SliderDicer feature of the University of Virginia's EPIC Electronic Medical Record system, we identified 436 patients with documented use of belatacept. Six transplant patients (1.37%) were found to have developed de novo psoriasis following the initiation of this drug. The diagnosis of psoriasis was confirmed either clinically or through biopsy by the center's dermatologists. All patients had received anti-thymocyte globulin (ATG) induction and initial maintenance immunosuppression with tacrolimus, mycophenolate mofetil (MMF), and prednisone. Belatacept was introduced later in the transplant course for reasons of non-adherence, calcineurin inhibitor (CNI)-related side-effects, or as additional immunosuppressive therapy. Table 1 provides a comparative summary of patients’ psoriasis presentation, time of onset, and management. Medication noncompliance with cardiac rejection. 4-drug regimen to increase baseline immunosuppression. Triamcinolone 0.1%, Betamethasone dipropionate 0.05%, Calcipotriene 0.005% The average age of recipients at the time of psoriasis presentation was 36.3 years (range: 21–67 years), with an average delay of 2.15 years (range: 1–3 years) from the initiation of belatacept to disease onset. Patients were diagnosed with various subtypes of psoriasis, including guttate (2), inverse (2), and plaque (2) (Figure S1). In all patients, psoriasis was limited to cutaneous disease, with no systemic features, including arthritis. Three of six patients had moderate to severe psoriasis, requiring systemic biological therapies. The psoriasis treatment for our patients was proportional to disease severity. Topical therapy sufficed for two patients, while the remaining four patients required systemic medications, three of whom were treated with biological agents. Biologic therapy for Patient 5 was discontinued due to increased suicidal ideation; however, the other patients were able to continue their treatments without serious adverse effects. All patients maintained good kidney allograft function and, importantly, were able to continue to use belatacept. Collaboration between dermatology and transplant teams allowed for a careful balance immunosuppression needs and psoriasis management. Psoriasis features overactivation of the T helper (Th) -17 pathway, with increased production of various cytokines, including tumor necrosis factor-alpha and interleukins (IL) 17, 22, and 23 [3, 4]. Belatacept, a T-cell-specific agent, disrupts immune homeostasis, and several hypotheses have been proposed to explain its role in psoriasis induction. Both belatacept and its precursor drug, abatacept, decrease regulatory T cell (T-regs) counts in human and animal models in vitro. This effect may stem from the drug's dual impact on inhibiting T-cell proliferation and interfering with T-reg generation, potentially contributing to the development of psoriasis [3, 4]. Alternatively, belatacept may exert an “immune skewing” effect, reducing Th1 cell levels while amplifying Th17 cell levels [3, 5]. To our knowledge, this is the largest case series describing new-onset psoriasis following belatacept initiation in KTRs. This case series provides valuable information on psoriasis treatment in the transplant setting. Our case series raises awareness of this rare but significant manifestation of de novo psoriasis following belatacept initiation. Notably, it is the first to report this phenomenon in a heart-kidney transplant recipient. However, this study has limitations, including the small number of cases and limited data on psoriasis improvement after belatacept discontinuation. Another limitation is the lack of a comparison group to establish the baseline rate of de novo psoriasis in the general solid organ transplant population. Future studies presenting cases where psoriasis improves following belatacept withdrawal could further bolster causality evidence. The variable onset and morphology underscore the need for constant vigilance to ensure timely diagnosis and treatment initiation. With appropriate treatment, patients may achieve reasonable control of their psoriasis while continuing belatacept. Further, biologics were not associated with increased infectious complications in our transplant cohort. Collaboration between dermatologists and transplant clinicians is key to recognizing and successfully controlling psoriasis while continuing the most appropriate immunosuppressive therapy. Dr. R. Hal Flowers serves as a principal investigator for AbbVie, Acelyrin, AstraZeneca, Clinuvel, Regeneron/Sanofi, and Sun Pharmaceuticals. He has served on advisory boards for Argenx, Bristol-Myers Squibb, and Janssen. Dr Swati Rao has the following research funding: (1) A 12-month, Randomized, Open-Label, Phase IIA Study Evaluating the Safety and Efficacy of Siplizumab in Combination With Belatacept and MPA Compared to Standard of Care Immunosuppression in de Novo Renal Transplant Recipients (ASCEND), sponsored by ITB-MED, Site-PI (2023-present); (2) Assessment of Biomarker Guided CNI Substitution in Kidney Transplantation, sponsored by NIH, Site Sub-PI (2023-present) The data that support the findings of this study are available on request from the corresponding author. 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