COVID-19 antiviral therapy for non-hospitalized immunosuppressed patients with rheumatic diseases is feasible with positive outcomes

Dear Editor, Patients with immune-mediated inflammatory diseases (IMIDs) are at increased risk of severe COVID-19 [1, 2] and can mount suboptimal immune responses to vaccination [3, 4]. Extrapolating from studies of unvaccinated individuals, novel therapies including neutralizing monoclonal antibodies (e.g. sotrovimab) and SARS-CoV-2 antivirals (e.g. nirmatrelvir/ritonavir, molnupiravir) offer potential options to reduce the risk of severe COVID-19 in immunosuppressed individuals, thereby reducing hospitalizations, morbidity and mortality.

In December 2021, an interim clinical commissioning policy was issued by the UK chief medical officers recommending these therapies to treat symptomatic COVID-19 in non-hospitalised patients in specific high-risk groups, including patients with IMIDs receiving specific potent immunosuppressants [such as cyclophosphamide, biologics, JAK inhibitors, mycophenolate mofetil, and high dose (≥10 mg/day) prednisolone] [5]. Regional COVID Medicines Delivery Units (CMDUs) were established to facilitate assessment and treatment, supported by input from local specialist medicine services. We describe here the characteristics, treatment and outcomes of treatment of COVID-19 in non-hospitalized patients with rheumatic musculoskeletal disease (RMD) referred to our centre: a large tertiary rheumatology unit in the North East of England.

Patients were referred from the regional CMDU and general rheumatology advice lines for same-day telephone assessment by a rheumatology consultant or nurse specialist at Newcastle Hospitals based on their postcode and usual treating rheumatology unit. Treatment was offered to patients with an RMD and symptomatic SARS-CoV-2 infection (confirmed by PCR or lateral flow) within 5 days of symptom onset (extendable to 7 days at clinician discretion), according to local implementation of the prevailing national policy (initially molnupiravir or sotrovimab, followed by addition of nirmatrelvir/ritonavir from 10 February 2022 onwards). Personalized clinical advice including temporary suspension of immunosuppressive medication, adjustment of steroid dosage, and instructions on actions to take in event of clinical deterioration was provided to each patient. Clinical details were contemporaneously documented at the time of assessment; subsequent emergency hospital attendance within 28 days of symptom onset, and deaths up to 31/07/22, were retrospectively recorded with reference to electronic patient records. The study was registered with Newcastle Hospitals as a clinical service evaluation (13757) with Caldicott approval (9595). Patient consent was not required for anonymized data analysis after removal of patients registered via the NHS national data opt-out service.

Between 17 January 2022 and 30 June 2022, 507 patients were referred for assessment, of which 30 were excluded from analysis (27 patient data opt-out, three missing data). The remaining 477 patients encompassed a wide range of RMDs and immunosuppressive therapies (Table 1, Supplementary Table S1, available at Rheumatology online). Three patients had confirmed infection on two separate occasions >28 days apart (virus genotype unknown). Data on previous SARS-CoV-2 vaccinations were available for 454 patients; the majority (427, 94%) had received at least three SARS-CoV-2 vaccine doses. Patients were assessed within a median (IQR) of 3(2–4) days after symptom onset (information available for 406 assessments). Of the 248 patients eligible for treatment, 80 (32%), 98 (40%) and 57 (23%) received nirmatrelvir/ritonavir, sotrovimab or molnupiravir, respectively. Sixteen patients who were potentially eligible for antivirals did not receive treatment: 12 due to patient choice, three due to being asymptomatic by time of assessment, and one due to hospital admission immediately after assessment.

Clinical outcomes in our cohort were largely favourable. Twenty-seven (6%) patients required emergency hospital assessment within 28 days of assessment; further clinical information was available for 22 of these patients, of whom 15 attended due to COVID-19 symptoms and six (1.3%) required hospital admission (Supplementary Table S2, available at Rheumatology online). One patient died 3 months after infection due to comorbid follicular lymphoma.

The limitations of our study include the relatively small sample size and limited inclusion period. Also, the high vaccine coverage limits inferences on clinical efficacy of the antiviral treatments.

In summary, our data demonstrate the feasibility of a rapid-access assessment and treatment pathway for the outpatient treatment of RMD patients with COVID-19, with overall positive clinical outcomes.

Supplementary material

Supplementary material is available at Rheumatology online.

Data availability

The data underlying this article cannot be shared due to legal restrictions to protect patient privacy.

Funding

K.F.B. is supported by a Newcastle Health Innovation Partners Senior Clinical Fellowship, and the Newcastle Hospitals Charity [8033 to KFB].

Disclosure statement: The authors have declared no conflicts of interest.

Acknowledgements

We are grateful for the support of medical, nursing and administrative colleagues in the rheumatology and infectious diseases departments for their clinical care of these patients and assistance with data recording.

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