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Vol. 114. Núm. 1.
Páginas T49-T53 (Enero 2023)
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Vol. 114. Núm. 1.
Páginas T49-T53 (Enero 2023)
Practical Dermatology
Open Access
[Translated article] Practical Guide to New Treatments for SARS-CoV-2 Infection in Dermatology Patients Being Treated With Common Immunomodulators
Guía práctica de las nuevas alternativas terapéuticas frente a SARS-CoV-2 en pacientes con inmunomoduladores de uso frecuente en Dermatología
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M. Viedma-Martínez
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, G. Gallo-Pineda, D. Jiménez-Gallo
Servicio de Dermatología, Hospital Puerta del Mar, Cádiz, Spain
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M. Viedma-Martínez, G. Gallo-Pineda, D. Jiménez-Gallo
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Abstract

Immunosuppressants and immunomodulators are widely used in dermatology. Some of these drugs, however, can increase the risk of severe COVID-19. New antivirals against SARS-CoV-2 have been shown to reduce progression to COVID-19 pneumonia in susceptible patients, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy. In this practical guide, we review the indications for these new drugs and provide guidance on which patients with mild to moderate COVID might benefit from their use in dermatology.

Keywords:
COVID
Immunosuppressants
Paxlovid
Resumen

En Dermatología es frecuente el uso de inmunosupresores e inmunomoduladores, algunos de los cuales pueden predisponer al desarrollo de enfermedad grave por SARS-CoV-2. Las nuevas terapias antivirales frente al SARS-CoV-2 han demostrado reducir la progresión a neumonía por COVID-19 grave en pacientes susceptibles. El pasado 23 de mayo, la Agencia Española de Medicamentos y Productos Sanitarios publicó la última actualización sobre los criterios para la priorización en el acceso precoz a estos fármacos debido a su limitada disponibilidad. En esta guía práctica revisamos los pacientes dermatológicos que en caso de contraer COVID-19 leve-moderada pueden beneficiarse de los nuevos antivirales, así como su indicación.

Palabras clave:
COVID
Inmunosupresores
Paxlovid
Texto completo

Several antivirals are available for the treatment of SARS-CoV-2 infection, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy.1 In this practical guide, we review the indications for these drugs and provide guidance on which dermatology patients with mild to moderate COVID-19 could benefit from their use.

Immunosuppressants and immunomodulators are widely used in dermatology, but a number of these drugs may increase the risk of severe COVID-19.2,3 New antivirals have been shown to reduce progression to severe COVID in patients on immunomodulators classified as high risk.4 The following immunomodulators, all frequently used in dermatology, have been classified as high risk by the AEMPS (Table 1): high-dose or long-term corticosteroids; immunosuppressive drugs administered in the previous 3 months; and certain immunomodulatory biologics administered in the previous 3 months (or previous 6 months in the case of anti-CD20 therapy). Patients on immune checkpoint inhibitors and other cancer treatments that do not increase infection risk, such as targeted therapy drugs for melanoma and hedgehog pathway inhibitors, are not eligible for new antivirals according to the AEMPS priority criteria (Table 1). Finally, there are many immunomodulatory drugs commonly used in dermatology on which the AEMPS has not taken a position (Table 2). Evidence of their safety in COVID is scarce, although reports to date do not seem to indicate an increased risk of progression to severe disease. Some authors have even proposed that some of these drugs may help curb the cytokine storm induced by the virus.5,6

Table 1.

Immunomodulators Commonly Used in Dermatology Classified by Risk According to the Spanish Agency for Medicines and Medical Devices (AEMPS).

High risk  Treatment with oral corticosteroids (prednisolone) in any of the following regimens in previous 30 days:• ≥10mg/d for >4 consecutive weeks• ≥10mg/d for >10 consecutive weeks• ≥10mg/d for >7 consecutive days 
  Treatment with nonbiologic immunomodulators in previous 3 months:• Oral or subcutaneous methotrexate >20mg/wk or >15mg/m2/wk• 6-Mercaptopurine>1.5mg/kg/d• Azathioprine>3mg/kg/d• Cyclosporine• Mycophenolate• Tacrolimus• Sirolimus• Everolimus 
  Treatment with any of the following immunomodulatory biologics in previous 3 months (or 6 months in the case of anti-CD20 therapies):• Anti-CD20 monoclonal antibodies: rituximab• Anti-CCR4 monoclonal antibodies: mogamulizumab• T-cell inhibition fusion proteins: abatacept• Interleukin 1 inhibitors: anakinra, canakinumab, and rilonacept• Anti-CD52 monoclonal antibodies: alemtuzumab• Protein kinase inhibitors: imatinib• Janus kinase inhibitors: tofacitinib, baricitinib, upadacitinib 
Low risk  • Immune checkpoint inhibitors: pembrolizumab, nivolumab, avelumab, cemiplimab• Targeted therapy drugs: dabrafenib-trametinib, vemurafenib-cobimetinib, encorafenib-binimetinib• Hedgehog pathway inhibitors: vismodegib, sonidegib 
Table 2.

Immunomodulatory Drugs Used in Dermatology That Have Not Been Classified by the Spanish Agency for Medicines and Medical Devices (AEMPS).

Immunomodulatory drugs  Target 
Adalimumab, etanercept, infliximab, certolizumab  TNF-α 
Dupilumab  Interleukin 4/13 
Tocilizumab  Interleukin 6 
Ustekinumab  Interleukin 12/23 
Ixekizumab, secukinumab, brodalumab  Interleukin 17 
Guselkumab, tildrakizumab, risankizumab  Interleukin 23 
Omalizumab  Immunoglobulin E 
Apremilast  Phosphodiesterase 4 

New treatment options for SARS-CoV-2 infection can be divided into 2 classes (Table 3): antivirals and monoclonal antibodies. Antivirals include nirmatrelvir/ritonavir (Paxlovid), remdesivir (Veklury), and molnupiravir (Lagevrio), which block enzymes that are crucial to viral replication.7–9 Monoclonal antibodies include casirivimab/imdevimab (Ronapreve) and sotrovimab (Xevudy), which bind to different epitopes on the spike protein of SARS-CoV-2, preventing the virus from entering human cells.4,10 These drugs are indicated for all patients with mild to moderate COVID-19 who do not require hospital admission and who are being treated with any of the high-risk immunomodulators mentioned, regardless of vaccination status.

Table 3.

New Treatment Options for SARS-CoV-2 Infection.

Drug  Type  Time of administration  Administration route  Dosage 
Nirmatrelvir/ritonavirPaxlovid  Antiviral  First 5 days  Oral  300mg nirmatrelvir+100mg ritonavir every 12h, 5 d 
RemdesivirVeklury  Antiviral  First 7 days  Intravenous  Day 1: 200mgDays 2 and 3: 100mg 
Molnupiravir(Lagevrio)  Antiviral  First 5 days  Oral  800mg every 12h, 5 d 
Casirivimab/imdevimabRonapreve  Monoclonal antibodies  First 7 days  Intravenous or subcutaneous  600mg casirivimab+600mg imdevimab, single dose 
SotrovimabXevudy  Monoclonal antibodies  First 5 days  Intravenous  500mg, single dose 

For adults (Fig. 1), the AEMPS recommends nirmatrelvir/ritonavir for 5 days as the treatment of choice because it is effective, easy to prescribe, and readily accessible. Drug-drug interactions are the main contraindication, as ritonavir is a strong inhibitor of cytochrome CYP3A.7 Choice of drug for patients in whom nirmatrelvir/ritonavir is contraindicated (Table 4) depends on immunoglobulin G titers against the SARS-CoV-2 spike protein. Monoclonal antibodies are the first-line option for patients with a titer of less than 260 binding antibody units per milliliter, while antivirals are indicated for patients with higher titers or for whom serology is not available. Choice of monoclonal antibody depends on the SARS-CoV-2 variant suspected. When omicron is suspected, the treatment of choice is sotrovimab, the only monoclonal antibody to have shown in vitro neutralizing activity against this variant.11 In other cases, casirivimab/imdevimab is used. The antiviral of choice is remdesivir. When this is not available, molnupiravir, an unauthorized drug with a use recommendation from the Committee for Medicinal Products for Human Use, can be used. Monoclonal antibodies and antivirals should both be started within 5 to 7 days of symptom onset.

Figure 1.

Treatment algorithm for new antivirals against SARS-CoV-2 in adults (adapted from Spanish Agency for Medicines and Medical Devices [AEMPS] guidance). BAU indicates binding antibody units; Ig, immunoglobulin.

(0,28MB).
Table 4.

Drug Interactions with Paxlovid (Based on Summary of Product Characteristics).

Main active ingredients that are contraindicated with paxlovid
Fusidic acid  Diazepam  St. John's wort  Propoxyphene 
Alfuzosin  Dihydroergotamine  Lomitapide  Quetiapine 
Amiodarone  Dronedarone  Lovastatin  Quinidine 
Astemizole  Encainide  Lurasidone  Ranolazine 
Avanafil  Ergonovine  Methylergonovine  Rifampicin 
Bepridil  Ergotamine  Midazolam oral  Sildenafil 
Carbamazepine  Estazolam  Neratinib  Simvastatin 
Cisapride  Phenytoin  Pethidine  Terfenadine 
Clorazepate  Phenobarbital  Pimozide  Triazolam 
Clozapine  Flecainide  Piroxicam  Vardenafil 
Colchicine  Flurazepam  Propafenone  Venetoclax 
Main active ingredients that require close monitoring
Abemaciclib  Delamanid  Itraconazole  Risperidone 
Afatinib  Dexamethasone  Ketoconazole  Rivaroxaban 
Alprazolam  Desipramine  Lamotrigine  Rosuvastatin 
Amitriptyline  Digoxin  Levothyroxine  Salmeterol 
Amlodipine  Diltiazem  Loratadine  Sertraline 
Amphetamine  Divalproex  Maraviroc  Sulfamethoxazole/ 
Apalutamide  Efavirenz  Methadone  Trimethoprim 
Atorvastatin  Encorafenib  Parenteral midazolam  Tacrolimus 
Atovaquone  Erythromycin  Morphine  Tadalafil 
Bedaquiline  Ethinylestradiol  Nifedipine  Theophylline 
Bosentan  Everolimus  Nilotinib  Thioridazine 
Budesonide  Fentanyl  Norbuprenorphine  Triamcinolone 
Buprenorphine  Fexofenadine  Nortriptyline  Vinblastine 
Bupropion  Fluoxetine  Paroxetine  Vincristine 
Buspirone  Fostamatinib  Prednisolone  Vorapaxar 
Ceritinib  Glecaprevir/pibrentasvir  Propionate fluticasone  Voriconazole 
Ciclosporin  Haloperidol  Raltegravir  Warfarin 
Clarithromycin  Ibrutinib  Rifabutin  Zidovudine 
Dasatinib  Imipramine  Riociguat  Zolpidem 

Remdesivir is also the treatment of choice for pediatric patients under the age of 12 years or weighing less than 40kg (Fig. 2). Classes of drugs other than monoclonal antibodies should be considered in patients whose condition is worsening despite remdesivir.

Figure 2.

Treatment algorithm for new antivirals against SARS-CoV-2 in pediatric patients (adapted from Spanish Agency for Medicines and Medical Devices [AEMPS] guidance).

(0,12MB).

In conclusion, immunomodulators are a mainstay treatment for many patients in dermatology, where inflammatory and autoimmune disorders are common. Dermatologists must be familiar with the treatments available for SARS-CoV-2 infection, as some of their patients might be in a high-risk situation. We hope that this guide will help.

Funding

The authors declare that there was no funding from any entity in this research.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References
[1]
Criterios para valorar la administración de las nuevas alternativas terapéuticas antivirales frente a la infección por SARS-CoV-2. Agencia Española de Medicamentos y Productos Sanitarios; 2022. Available from: https://www.aemps.gob.es/medicamentos-de-uso-humano/acceso-a-medicamentos-en-situaciones-especiales/criterios-para-valorar-la-administracion-de-las-nuevas-alternativas-terapeuticas-antivirales-frente-a-la-infeccion-por-sars-cov-2/ [Cited 2022 Jun 5].
[2]
K. Price, J. Frew, J. Hsiao, V. Shi.
COVID-19 and immunomodulator/immunosuppressant use in dermatology.
J Am Acad Dermatol, 82 (2020), pp. e173-e175
[3]
M. Fung, J.M. Babik.
COVID-19 in immunocompromised hosts: what we know so far.
Clin Infect Dis, 72 (2021), pp. 340-350
[4]
A. Gupta, Y. Gonzalez-Rojas, E. Juarez, M. Crespo Casal, J. Moya, D.R. Falci, et al.
Early treatment for covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab.
N Engl J Med, 385 (2021), pp. 1941-1950
[5]
S. Cafarotti.
Severe acute respiratory syndrome-coronavirus-2 infection and patients with lung cancer: the potential role of interleukin-17 target therapy.
J Thorac Oncol, 15 (2020), pp. e101-e103
[6]
V. Bulat, M. Situm, M. Azdajic, R. Likic.
Potential role of IL-17 blocking agents in the treatment of severe COVID-19?.
Br J Clin Pharmacol, 87 (2020), pp. 1578-1581
[7]
Y. Lamb.
Nirmatrelvir plus ritonavir: first approval.
[8]
S. Moreno, B. Alcázar-Navarrete, C. Dueñas, J. González del Castillo, J. Olalla, A. Antela.
Use of antivirals in SARS-CoV-2 infection critical review of the role of remdesivir.
Drug Des Devel Ther, 16 (2022), pp. 827-841
[9]
M. Imran, M. Kumar Arora, S.M.B. Asdaq, S.A. Khan, S.I. Alaqel, M.K. Alshammari, et al.
Discovery development, and patent trends on molnupiravir: a prospective oral treatment for COVID-19.
Molecules, 26 (2021), pp. 5795
[10]
E. Deeks.
Casirivimab/imdevimab: first approval.
Drugs, 81 (2021), pp. 2047-2055
[11]
T.T. Brehm, S. Pfefferle, R. von Possel, M. Karolyi, A. Zoufaly, D. Wichmann, et al.
Clinical efficacy and in vitro neutralization capacity of monoclonal antibodies for SARS-CoV-2 delta and omicron variants.
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