Impact of COVID-19 Pandemic on the Care of Patients With axSpA

Introduction

The current pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented unprecedented hurdles to the healthcare systems in almost every country around the world. In this section, the term COVID‐19 is the name of the disease caused by SARS–CoV‐2. It has a wide clinical spectrum that includes fever, dry cough, myalgia, arthralgia and fatigue in its early or mild form and dyspnea and bilateral ground-glass opacities on chest computed tomography (CT) scans in the most severe form. Even though the clinical picture of severe COVID-19 resembles that of acute respiratory distress syndrome (ARDS), the lung histopathological findings suggest that COVID-19 can cause a specific form of alveolar disease that is distinct from ARDS.

This pandemic has posed unique challenges to rheumatologists. Ankylosing spondylitis (AS) does not appear to confer unique susceptibility or result in greater severity from COVID-19. A limited number of cases of acute arthritis or dactylitis have also been reported in association with COVID-19, including reactive arthritis in six cases, and crystal-induced arthritis flare-up in four patients. Children and adolescents develop only mild influenza-like symptoms, but in rare cases, Kawasaki-like disease can occur as a complication of COVID-19. Early in the pandemic, a temporary shortage of some drugs, such as hydroxychloroquine (HCQ) and tocilizumab, was noted due to their off-label use by some to prevent or treat COVID-19.

A recent systematic review pointed out that 19% of COVID-19 cases might present with musculoskeletal pain as their initial symptom, and such cases, in the absence of other more typical symptoms of COVID-19, may come to the attention of rheumatologists. During differential diagnosis, it should be kept in mind that COVID-19 patients can commonly test positive for anti‒52 kDa SSA/Ro antibody, anti‒60 kDa SSA/Ro antibody and antinuclear antibody (20%, 25% and 50%, respectively). Anti-cardiolipin and/or anti-β2-glycoprotein I antibodies were detected in 7 of 31 (23%) consecutive confirmed COVID-19 patients admitted in an intensive care unit.

It is well known that joint complaints such as arthralgia, arthritis, tenosynovitis and myalgia may occur during the course of any viral infection but they are generally transient and self-limiting, with the exception of those associated with chikungunya and some of the other viruses, including hepatitis B virus and C, rubella and parvovirus. Arthritis accompanying such viral infections present with characteristic features resulting from direct invasion of the affected joints and/or formation of circulating immune-complexes, but SARS-CoV-2 viremia occurs only in about 15% of COVID-19 cases. The mild-to-modest musculoskeletal symptoms may be indistinguishable from those associated with other respiratory viruses, but COVID-related arthralgia is reported in <10% , whereas 44% experience myalgia.

No increase in susceptibility to COVID-19 was observed among patients with ankylosing spondylitis/ axial spondyloarthritis (AS/axSpA), or with any drug class used for its treatment, and only a little correlation was found between disease activity and severity of COVID-19 (Figure 19-1). Moreover, there is no effect of HLA-B27 on susceptibility and severity of COVID-19.

The major questions for rheumatologists are about how to advise rheumatic disease patients to initiate or continue immunomodulative treatments and avoid the risk of contracting COVID-19. While of late, it has been also about how to use the COVID-19 vaccine. The constraints imposed by the pandemic on the delivery of rheumatology care at hospitals, combined with the patients’ reluctance to go to hospitals have had disruptive effects on the standard of their care, including for those with axial spondyloarthritis (axSpA) as shown in a study from United kingdom (UK). And in a survey from France, >60% of participants reported a worsening of spondyloarthritis (SpA) during the lockdown period, mainly due to reduction of treatment and possibly also from loss of physical activity. Another survey in the United States (US) showed that roughly one in four patients on a biologics (tumor necrosis factor inhibitors (TNFis) or IL-17is) either discontinued or reduced the dose of their medication in the absence of contracting COVID-19.

As the pandemic has evolved and new data have emerged, it can be stated that it is not the diagnosis of chronic inflammatory joint disease but the patient’s age, disease-associated comorbidities and high disease activity that are the risk factors for serious COVID-19-related outcomes. Among the 3,729 patients enrolled in the COVID-19 Global Rheumatology Alliance, 10.5% mortality was observed and that was associated with older age, male gender, high disease activity and also among those receiving immunosuppressants (rituximab, azathioprine, cyclophosphamide, mycophenolate) and sulfasalazine (SSZ). There was no association with the use of biologics and disease-modifying antirheumatic drugs ( DMARDs).

The increased mortality with SSZ in the Global Rheumatology Alliance Study is surprising given its mild immunosuppressive effects, and the authors did state that any causal interpretation between SSZ and COVID-19 related death should not be made. Recent data from Swedish nationwide multi-register linkages found no such association of SSZ and other antirheumatic drugs with mortality, with the possible exception of rituximab and Janus kinase inhibitors (JAKis), but risks specifically in relation to glucocorticoids use could not be assessed in this study for methodological reasons. The risk of hospitalization due to COVID-19 among patients with chronic inflammatory arthritis was 0.5% vs 0.3% in the general population, their admission to intensive care was 0.04% vs 0.03% and mortality was 0.10% vs 0.07%. The results of this Swedish study may be considered more reliable than those based on surveys (which may miss fatal cases) or hospital queries (which may miss cases dying out of hospitals).

Based on the accumulated evidence, American College of Rheumatology (ACR) has recently published the third version of its COVID-19 guidance on the management of adult rheumatic disease patients, as more data have become available. These recommendations, summarized in Tables 19-1 to 19-5, are presented as general statements for all rheumatic diseases and address the use of various anti-rheumatic drugs in different scenarios, including when to start, stop, or reduce the dose. The following recommendations in particular may be relevant for patients with SpA:

• As part of a shared decision‐making process and to reduce health care encounters and potential exposure to SARS–CoV‐2 (beyond general preventive measures), it may be reasonable to reduce frequency of laboratory monitoring, widen dosing intervals between intravenous medications and increase optimal use of telehealth (Table 19-1).
• Patients with stable disease may continue their ongoing treatment including NSAIDs, DMARDs or biologic drugs (Table 19-2).
• In the absence of infection or known SARS–CoV‐2 exposure, biologics may be started in patients with moderate‐to‐high disease activity despite optimal conventional synthetic DMARDs. If indicated, NSAIDs may be started (Table 19-3).
• NSAIDs and SSZ may be continued following SARS–CoV‐2 exposure. In the case of documented or presumptive COVID-19, all DMARDs, non–IL-6 biologics and JAKi should be stopped or withheld, regardless of COVID-19 severity. NSAIDs should be stopped in patients with severe respiratory symptoms (Table 19-4).
• For patients with uncomplicated COVID‐19 (characterized by no or mild pneumonia and treated in the ambulatory setting or via self‐quarantine), consideration may be given to restarting rheumatic disease treatments within 7-14 days of symptom resolution (Table 19-4).

The ACR has also released a COVID-19 vaccine guidance summary to provide official recommendations for rheumatology patients. In this guidance all patients with rheumatic diseases are recommended to receive COVID-19 vaccination, in accordance with the age restriction of the Emergency Use Authorization and/or Food and Drug Administration (FDA) approval. No modifications were recommended for either immunomodulatory drugs used in the treatment of SpA, such as SSZ, TNFis and IL17is or vaccination timing (Table 19-5).

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