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HomeInfectious DiseasesMpox drug SAE only in compromised patients – CDC study

Mpox drug SAE only in compromised patients – CDC study

An analysis by the US Centres for Disease Control & Infection on the use of Tpoxx – the antiviral drug tecovirimat prescribed to more than 7 100 American mpox patients in 2022 and 2023 – found few serious adverse events, with most of these occurring in patients with weakened immune systems, said the agency.

However, the authors cautioned that tecovirimat safety and effectiveness can’t be determined from the data, gathered during the global outbreak of mpox caused by the clade 2 virus that peaked in 2022.

The investigators parsed data on the characteristics, clinical courses, and outcomes from the intake and outcome forms and diaries of patients from 49 US states prescribed tecovirimat from May 2022 to July 2023.

Amid that outbreak, reports CIDRAP, many US patients were prescribed tecovirimat, stockpiled by the government for a potential reintroduction of smallpox, under an expanded-access Investigational New Drug (EA-IND) programme.

Skin, anogenital region most affected

Most of the roughly 7 100 patients were prescribed a 14-day course of tecovirimat for the treatment of lesions in sensitive areas, such as the anogenital region (83.5%), and for pain (52.5%). Most patients who received tecovirimat were men with a median age of 35 but cases were also seen in women (220 patients), pregnant women (12) and children under 12 (17).

The median time from symptom onset to tecovirimat prescription was seven days. Clinicians reported that 77.1% of mpox patients had a rash at illness onset. The skin (76.3%) and anogenital region (73.1%) were the most commonly affected areas at baseline, but lesions in the mouth (17.3%) and eyes (4.2%) were also reported.

Of the 7 181 patients with returned intake forms, 22.6% also had returned outcome forms. A total of 223 SAEs (3.1%) and 40 deaths (0.6%) were reported, mainly among those with severely weakened immune systems, and 3.9% were hospitalised.

In addition to death, the most common SAEs were headache, nausea, vomiting, elevated liver enzymes, hives, fatigue, acute kidney injury, abdominal pain, dizziness and tremor.

Children, pregnant women, and those with conditions compromising skin integrity didn’t have severe outcomes, reported the researchers in their paper, published in NEJM Evidence.

Half also had HIV

Many patients with HIV and low CD4 white blood cell counts (22 of 51 [43.1%]) were given multiple tecovirimat courses, some of them intravenous, and often had poor outcomes (18 of 51 [35.3%]). One severely immunocompromised patient reported hallucinations after receiving twice the recommended dose of tecovirimat.

Roughly 52% of people with returned intake forms had HIV, and 8.5% had other underlying illness; of the latter, 4.3% had severely weakened immune systems (including 277 HIV patients with low CD4 counts), 4.2% had conditions affecting skin integrity (atopic dermatitis or eczema (240 patients), psoriasis (40), cystic acne (4), and other conditions (15).

Of HIV patients with low CD4 counts, 11 had another condition that met the definition of severe immunocompromise (10 with cancer and one with a solid-organ transplant).

In total, 15.1% of patients (128 of 846) had received the Jynneos mpox vaccine before reported mpox exposure. The median number of lesions at intake after receipt of one dose of Jynneos was seven.

“The EA-IND data are not definitive; controlled clinical trial data are essential to elucidating if and how tecovirimat should be used,” the study authors cautioned.

Study details

Tecovirimat Use under Expanded Access to Treat Mpox in the United States, 2022–2023

Patricia Yu, Riad Elmor, Kalimah Muhammad, Yon Yu, and Agam Rao.

Published in NEJM Evidence on 13 September 2024

Background
During the ongoing outbreak of clade II monkeypox virus (MPXV), many US patients were prescribed tecovirimat, an antiviral drug that was made available under an expanded access Investigational New Drug (EA-IND) programme. We evaluated EA-IND data to summarise characteristics of treated patients, outcomes, and serious adverse events (SAEs).

Methods
We evaluated data from patients prescribed tecovirimat from May 29, 2022, through July 10, 2023. Baseline patient characteristics, clinical courses, and outcomes were evaluated via intake forms, outcome forms, and patient diaries. Data were summarized in aggregate by human immunodeficiency virus (HIV) status and by comorbidities of special interest. Reported SAEs were also compiled.

Results
Tecovirimat was prescribed for over 7100 patients in the United States, most often for lesions in sensitive anatomical areas, such as certain anogenital lesions (83.5%; 5135 out of 6148 patients), and pain (52.5%; 3227 out of 6148 patients). The demographic and clinical characteristics mirrored those of patients worldwide. Among the 7181 patients with returned intake forms, 1626 also had returned outcome forms (22.6%). Many patients with severe immunocompromise (e.g., HIV with CD4 counts <200 cells/μl) received multiple courses of tecovirimat (43.1%; 22 out of 51 patients), including intravenously, and often experienced poor outcomes (35.3%; 18 out of 51 patients). Overall, 223 SAEs and 40 deaths were reported. Most SAEs were among patients who were severely immunocompromised, one of whom experienced hallucinations after tecovirimat was administered at twice the standard dose.

Conclusions
Tecovirimat was used extensively. The returned EA-IND data suggest that life-threatening or protracted infections occurred in persons who were severely immunocompromised. SAEs were not commonly reported. The EA-IND data are not definitive; controlled clinical trial data are essential to elucidating if and how tecovirimat should be used.

 

NEJM Evidence article – Tecovirimat Use under Expanded Access to Treat Mpox in the United States, 2022–2023 (Open access)

 

CIDRAP article – Poor outcomes after Tpoxx mpox treatment mainly seen in those with weak immunity (Open access)

 

See more from MedicalBrief archives:

 

Hope for Africa as WHO approves first mpox vaccine

 

Lessons – and mysteries – from fast-disappearing mpox

 

Don’t delay mpox vaccine roll-out, experts urge health authorities

 

Phaala warns against prejudice as SA records two monkeypox cases

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