What are the current treatment recommendations for Mpox infections?
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Introduction
Mpox (formerly known as monkeypox) is a disease caused by the Monkeypox virus, which is closely related to smallpox. 1 Mpox was declared a public health emergency of international concern (PHEIC) in July 2022 primarily due to clade IIb mpox, but ended in May 2023 when a sustained decline in global cases was observed. 2 However, in August 2024, the World Health Organization re-declared the mpox outbreak a PHEIC. Clinical presentation of mpox is characterized by a painful rash that starts as disseminated skin lesions and progresses from a macule rash to a papule, vesicle, pustule-like rash, then to a scab. 3 During the 2022 outbreak, presentation was reported to occur usually with at least 1 systemic symptom, such as lymphadenopathy or other prodrome symptom such as fever, headache, myalgias, or malaise. While most patients experience minimal symptoms, patients with moderate-to-severe immunosuppression, particularly those with advanced HIV, may experience severe symptoms. These severe symptoms include ocular lesions, neurologic complications, myopericarditis, and mucosal lesion-related complications. 1
Patients with minimal symptoms usually recover fully regardless of treatment and can be managed using supportive care and analgesics. 3 Skin and genital lesions can be managed with gentle washing, followed by application of petroleum jelly. Dressings can be used for persistent lesions, and antibiotics may be needed for bacterial superinfections. Oropharyngeal lesions can be managed with antiseptic mouthwash, viscous lidocaine, saltwater gargles, and analgesics such as anti-inflammatory agents and opioids. For patients with proctitis, supportive care includes stool softeners, lidocaine gel, sitz baths, and analgesics.
Patients who are immunocompromised, experience severe symptoms, or have lesions in high-risk locations (ie, eye or urethra) may benefit from medications used as medical countermeasures. 3 There are currently no FDA-approved treatments for mpox infection, but several treatments developed for smallpox and other orthopoxviruses have been suggested for use as medical countermeasures in close consultation with the Centers for Disease Control and Prevention (CDC). These include tecovirimat, brincidofovir or cidofovir, and vaccinia immune globulin intravenous (VIGIV).
Tecovirimat
Tecovirimat (TPOXX) is the preferred intervention if medical countermeasures are deemed appropriate for a patient. 1 It can be obtained through enrollment in the STOMP trial or via an expanded access-investigational new drug protocol. 4 Tecovirimat is an antiviral agent administered as 600 mg orally or IV twice daily (if weight is ≤ 120 kg) or three times daily (if weight is > 120 kg), typically for 2 weeks. 1 The duration may be extended based on patient specific factors and disease progression. Absorption of oral tecovirimat taken with a fatty meal is comparable to IV administration. Therefore, IV administration should be reserved for patients unable to take oral medication. Use is contraindicated in patients with a prior adverse effect with tecovirimat that would preclude its use or in patients with creatinine clearance < 30 mL/minute (for IV only).
Limited data is available evaluating the use of tecovirimat in humans for mpox (Table 1). 5-7 An interim analysis of a randomized controlled trial, PALM007 failed to show an improvement in patients with clade I mpox receiving tecovirimat in the Dominican Republic of the Congo. 5 Overall mortality reported in the trial was lower than typically reported mortality rates, signaling low external validity and better study conditions than usual care. Other noncontrolled trials describe treatment outcomes with tecovirimat, which may guide use in clinical practice, and support general safety of tecovirimat. Several studies are ongoing including the STOMP trial in patients with clade II mpox who are immunocompromised or at risk of developing severe disease. 4
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| Table 1. Data evaluating the use of tecovirimat in humans for mpox5-7 | ||||
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| Study design | Population | Interventions | Results | Limitations |
| PALM0075 – Ongoing PC, RCT | N=597 in the DRC with laboratory-confirmed clade I mpox | Tecovirimat vs. placebo for ≥ 14 days All patients were admitted to the hospital for the treatment period and received supportive care (nutrition, hydration, treatment of secondary infections) | Interim analysis did not show decreased duration of mpox lesions between treatment groups (results from interim analysis not available) Overall mortality in study: 1.7% | Mpox mortality in DRC is reported to be ≥ 3.6%, which is higher than that reported in PALM007, signaling that trial conditions do not represent typical care provided in DRC |
| Yu et al 20246 EA-IND | N=7181 patients with clade II mpox (72.4% treated outpatient) | Open-label tecovirimat | Hospitalization after starting tecovirimat (n=1043): 3.9% Tecovirimat given for > 14 days (n=1043): 3.7% Median duration to subjective improvement (n=337): 3 days (range 1 to 83, IQR 2 to 4) Median length of recovery (n=337): 10 days (range 1 to 45, IQR 7 to 14) Pain improvement on day 2 (n=90): 38.9% Complete pain resolution on day 9 (n=91): 52.7% Of the 310 patients with severe immunocompromise and outcome data: 43.5% were hospitalized at baseline, median duration of hospitalization was 17 days (IQR 7 to 38 days) Serious adverse events: Death: 40 patients (92.5% had severe immunocompromise) Other adverse effects: headache (n=12), nausea (n=10), vomiting (n=10), elevated liver enzymes (n=8), urticaria (n=8), fatigue (n=7), AKI (n=7), abdominal pain (n=6), dizziness (n=5), tremor (n=5) | No comparison arm Not all patients enrolled in EA-IND protocol had data available or data returned to the CDC |
| McLean et al 20237 Retrospective cohort | N=196 patients with confirmed mpox (47% with HIV infection, 53% without HIV infection) | Tecovirimat | New lesion after 48 hours in patients with HIV vs. no HIV: 15% vs. 20% (adjusted prevalence ratio, 0.94; 95% CI, 0.53 to 1.35) Pain resolved at end of treatment in patients with HIV vs. no HIV: 96% vs. 87% (adjusted prevalence ratio, 1.1; 95% CI, 0.49 to 1.7) Persistent symptoms at end of treatment in patients with HIV vs. no HIV: 24% vs. 36% (adjusted prevalence ratio, 0.73; 95% CI, 0.28 to 1.18) Hospitalization in patients with HIV vs. no HIV: 2.8% vs. 0% (no ratio reported) | Retrospective design Time from symptom onset to treatment was longer in patients without HIV (10 days vs. 7.5 days), potentially contributing to better outcomes in patients with HIV |
| Abbreviations: AKI=acute kidney injury; CDC=Centers for Disease Control and Prevention; CI=confidence interval; DRC=Dominican Republic of the Congo; EA-IND=expanded access investigational new drug program; HIV=human immunodeficiency virus; IQR=interquartile range; PC=placebo-controlled; RCT=randomized controlled trial. | ||||
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Brincidofovir and cidofovir
Brincidofovir is an oral prodrug of cidofovir and is FDA-approved for the treatment of smallpox.4 Cidofovir is available as an IV injection and is FDA-approved for treatment of cytomegalovirus retinitis in patients with AIDS. Either brincidofovir or cidofovir can be added to tecovirimat in patients with or at high risk of severe mpox.1 Monotherapy with either agent can be given if a patient has contraindications to tecovirimat. Therapy is given once weekly for a typical duration of 2 weeks, but longer doses may be administered based on an individual risk/benefit assessment. Brincidofovir and cidofovir should never be administered at the same time or within 1 week of each other as they form the same metabolite (cidofovir diphosphate) that has a long duration of action. Data evaluating brincidofovir and cidofovir in humans with mpox is limited to case reports. 8 Data in animal studies have demonstrated efficacy with brincidofovir, with a potential synergistic effect when administered with tecovirimat. 1,4
Vaccinia immune globulin intravenous
Vaccinia immune globulin intravenous may be given as a single IV dose in severe cases when a patient is not expected to mount an immune response capable of clearing the virus. 1,4 It is FDA-approved for treatment complications associated with vaccinia vaccination. Dosing can be repeated depending on the length of illness and severity of immunocompromise. There is no data regarding the benefit of VIGIV in patients with mpox infection, but the safety profile is favorable. Administration of VIGIV may also be considered as part of postexposure prophylaxis in patients with severe T-cell immunodeficiency when mpox vaccination is contraindicated.
Immunization overview
Given the lack of treatments for mpox, immunization plays a key role in the reducing the spread and, in turn, severity of infection. Current immunization guidelines from the CDC recommend pre-exposure vaccination in high-risk populations and post-exposure vaccination using Jynneos (smallpox and monkeypox live, non-replicating vaccine). 9 Pre-exposure vaccination is recommended in persons (1) with occupational risk factors, (2) with planned travel to a country with a clade I mpox outbreak with an additional risk factor (such as sex with a new partner, at a commercial sex venue, in exchange for goods, or associated with a large public event), and (3) who identify as gay, bisexual, men who have sex with men, transgender, nonbinary, or gender-diverse with an additional risk factors (such as new diagnosis of sexually transmitted disease, > 1 sexual partner, or sex at a commercial sex venue or an area where mpox transmission is occurring). Postexposure prophylaxis using Jynneos is recommended within 4 days after exposure.
Summary
While most patients with mpox infection can be managed using supportive care and pain management, some patients with severe infection and immunocompromise may require additional interventions. 1 Although no agents are FDA-approved for the treatment of mpox, tecovirimat can be given as the preferred intervention, and brincidofovir (or cidofovir if IV route is necessary) and/or VIGIV can be added in severe cases. Current data evaluating treatment options in humans is limited, and immunization is recommended as a key public health measure in high-risk populations.
References
1. Rao AK, Schrodt CA, Minhaj FS, et al. Interim clinical treatment considerations for severe manifestations of mpox – United States, February 2023. MMWR Morb Mortal Wkly Rep. 2023;72(9):232-243. doi:10.15585/mmwr.mm7209a4
2. World Health Organization (WHO). WHO Director-General declares mpox outbreak a public health emergency of international concern. WHO Website. Published August 14, 2024. Accessed October 14, 2024. https://www.who.int/news/item/14-08-2024-who-director-general-declares-mpox-outbreak-a-public-health-emergency-of-international-concern
3. McLean J, Gunaratne S, Zucker J. Update on mpox: what the primary care clinician should know. Med Clin North Am. 2024;108(2):355-371. doi:10.1016/j.mcna.2023.09.005
4. Centers for Disease Control and Prevention (CDC). Clinical treatment of Mpox. CDC Website. Updated September 13, 2024. Accessed October 23, 2024. https://www.cdc.gov/mpox/hcp/clinical-care/.
5. National Institute of Health (NIH). The antiviral tecovirimat is safe but did not improve clade I mpox resolution in Democratic Republic of the Congo. NIH website. Published August 15, 2024. Accessed October 21, 2024. https://www.nih.gov/news-events/news-releases/antiviral-tecovirimat-safe-did-not-improve-clade-i-mpox-resolution-democratic-republic-congo.
6. Yu PA, Elmor R, Muhammad K, Yu YC, Rao AK. Tecovirimat use under expanded access to treat mpox in the United States, 2022-2023. NEJM Evid. 2024;3(10):EVIDoa2400189. doi:10.1056/EVIDoa2400189
7. McLean J, Stoeckle K, Huang S, et al. Tecovirimat treatment of people with HIV during the 2022 mpox outbreak : A Retrospective cohort study. Ann Intern Med. 2023;176(5):642-648. doi:10.7326/m22-3132
8. Harrison I, DeSear K, Santevecchi BA, et al. Brincidofovir for disease progression due to suspected tecovirimat resistance in association with advanced HIV. Int J STD AIDS. 2024;35(8):651-653. doi:10.1177/09564624241238813
9. Centers for Disease Control and Prevention (CDC). Interim clinical considerations for use of vaccine for mpox prevention in the United States. CDC Website. Updated September 13, 2024. Accessed October 23, 2024. https://www.cdc.gov/mpox/hcp/vaccine-considerations/vaccination-overview.html.
Prepared by:
Amanda Gerberich, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy
November 2024
The information presented is current as October 23, 2024. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.