March 2025

Below is in response to the inquiry: My patient has been on Cimzia for about 2 years for plaque psoriasis, with their most common flare being underneath their eyes. They also failed Humira and Enbrel. They use Lotemax as a steroid for their eyes but are not comfortable using this long term, as it seems to calm the irritation but does not shrink the plaques. They also take vitamin D and get 20 minutes of direct sunlight a day to help. The last medication they tried and failed was a compounded Colchicine cream to put around the eyes that did not help. What therapy would you recommend for this patient to try next as well as any newer therapies that could be tried?

Plaque psoriasis is a chronic, inflammatory, immune-mediated disease affecting both adults and children that clinically presents with well-demarcated, red plaques with silvery scales.1  Psoriasis involves cutaneous T cells, dendritic cells, and keratinocytes with subsequent release of inflammatory cytokines. This means that psoriasis can affect virtually any part of the skin, therefore finding the right treatment regimen for patients is critical in preserving their quality of life. For patients who fail TNF-alpha blockers such as Humira or Cimzia, it is important to consider different biologic agents that mediate alternative targets in the disease pathological pathway.

Guselkumab, approved on July 13th, 2017, is a fully human IgG1 lambda monoclonal antibody that could be used as monotherapy for moderate to severe psoriasis.2 Guselkumab works by binding to the p19 subunit of IL-23 in dendritic cells and keratinocytes, which inhibits proliferation of IL-23, a pro-inflammatory cytokine. In comparison to its clinical competitor adalimumab, at the 16 week mark of a 48 week phase III trial (VOYAGE 2), a higher percentage of patients taking guselkumab achieved greater than 90% improvement in the Psoriasis Area and Severity Index (PASI) than patients on adalimumab or placebo (70.0% vs 46.8% vs 2.4%). Additionally, of non-responders to adalimumab that switched to guselkumab, 66.1% achieved an improvement of PASI over 90% at week 48. 

In comparison to secukinumab, an IL-17 inhibitor, patients in a phase III ECLIPSE trial showed that 84% in the guselkumab group achieved a PASI of 90% at week 48 compared to 70% in the secukinumab group.3 Despite having a slower initial response than secukinumab, there were more patients with improvements in their psoriasis condition taking guselkumab. 

Pre-treatment assessment and monitoring for biologics should be considered for guselkumab. Potential adverse effects include increased risk of infection, injection site reactions, and hypersensitivity. Regardless, the data presented above shows promising results that guselkumab can be an effective option for TNF-alpha blocker treatment resistant psoriasis such as that being experienced by this patient.

Reference: 

1. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics
   Menter, Alan et al. Journal of the American Academy of Dermatology, Volume 80, Issue 4, 1029 - 1072

2. Blauvelt, A., Chiricozzi, A., Ehst, B. D., & Lebwohl, M. G. (2023). Safety of IL-23 p19 Inhibitors for the Treatment of Patients With Moderate-to-Severe Plaque Psoriasis: A Narrative Review. Advances in Therapy., 40(8), 3410–3433. https://doi.org/10.1007/s12325-023-02568-0

3. Reich, K., Armstrong, A. W., Langley, R. G., Flavin, S., Randazzo, B., Li, S., Hsu, M.-C., Branigan, P., & Blauvelt, A. (2019). Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial. The Lancet., 394(10201), 831–839. https://doi.org/10.1016/S0140-6736(19)31773-8 

Hello Doctor,

Below is in response to the inquiry: A 43 year old male solid organ kidney post-transplant patient who is on Prograf 8mg PO every 12 hours, came into the clinic 8 months post transplant with extreme drowsiness, confusion, nausea, and elevated renal and liver function markers such as creatinine, blood urea nitrogen, and liver enzymes.The patient is on Vitamin B12 (past 8 months) and Folic Acid (past 8 months) which was prescribed as a supplement post renal transplant by our team. The patient also indicated that Paxlovid Standard Dose Pack 300mg :100mg (past 4 days) was initiated by an outside provider of the hospital, her PCP. The patient weight is 80kg with a GFR of 80mL/min. Can you tell me what is going on with this patient and if I can continue all his medications or if any adjustments need to be made based on his symptoms, lab values, and drug therapy he is on?

Patients who are Immunocompromised, such as those receiving solid organ transplant, are ideal candidates for treatment with antiviral medications. In this case, Paxlovid, was recommended to be taken by an outside provider of the hospital, her PCP. Paxlovid is an antiviral medication that contains nirmatrevir and ritonavir as ingredients used in the treatment of COVID-19. However, Ritonavir is considered a CYP3A4 inhibitor which can impact the effectiveness of the patient’s Prograf (tacrolimus) due to its metabolism being guided by CYP3A4. Paxlovid and tacrolimus can interact with one another leading to a potential significant increase in body tacrolimus levels.

Based on the patients’ current symptoms along with elevated liver enzymes, serum creatinine, and blood urea nitrogen levels, the patient can be experiencing problems related to elevated levels of tacrolimus. In a case report done in August of 2022, a kidney transplant patient took Paxlovid while resuming their normal immunosuppressant maintenance therapy including Tacrolimus, mycophenolate, and prednisone. However, while taking the Paxlovid, the patient experienced symptoms such as nausea and vomiting by day 2 and his tacrolimus levels were elevated, leading to the Paxlovid to be discontinued by day 3. Acutely high tacrolimus levels can lead to elevated creatinine levels and an acute kidney injury.

In this patient’s presentation the patient looks to be experiencing toxicity due to the increase in tacrolimus levels due to the Paxlovids impact. It is recommended that due to the severity of the symptoms and the increase in serum creatinine and liver enzymes, the Paxlovid should be discontinued to prevent worsening of the patients symptoms due to toxicity and injury to the kidney and or liver. For this patient with a GFR of 80 mL/min, the Paxlovid dose required no dose adjustment. If possible, the tacrolimus should have been held for 2-3 days while taking Paxlovid. The dose of prograf should also have been reduced to prevent acute increases in the levels while the patient took Paxlovid. Since the patient is experiencing symptoms of toxicity, the prograf and Paxlovid should be discontinued until the patient's symptoms are resolved and the levels of the tacrolimus and serum creatinine should be monitored until they return within normal limits. Once the tacrolimus levels are within normal therapeutic limits, the prograf therapy should be restarted.

Reference: 

Prikis, M., & Cameron, A. (2022). Paxlovid (nirmatelvir/ritonavir) and Tacrolimus Drug-drug interaction in a kidney transplant patient with Sars-2-cov infection: A case report. Transplantation Proceedings, 54(6), 1557–1560. https://doi.org/10.1016/j.transproceed.2022.04.015