Treating Rheumatic and Musculoskeletal Diseases During the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) pandemic has significantly changed the face of healthcare practice. Healthcare providers across the spectrum of medical practice have initiated emergency measures that have affected in-person patient consultation and new guidelines to provide a road map for chronic disease management. Patients with rheumatic and musculoskeletal diseases and healthcare practitioners who treat those diseases are no exception. As physicians and patients come to terms with the new normal, several questions emerge related to the delivery of care across the patient population.



The impact of SARS-CoV-2, the coronavirus responsible for COVID-19, has been global. As of September 18, 2020, almost 30 million coronavirus cases have been reported globally with approximately 943,000 deaths.3 Statistics for the United States alone reflect almost 7 million cases and more than 200,000 deaths.4 Furthermore, COVID-19 hospitalization and death rate ratios have been increasing staggeringly in every age group older than the 18- to 29-year-old age group.

The focus of this review is not a discussion of the reasons why, currently, the United States has the highest cumulative number of COVID-19 cases and deaths,5 with a projection to continue to increase into 2021.6 Rather, these statistics provide a window into the significant impact the pandemic is having and will continue to have on health care. These statistics also challenge the need to rethink the delivery of patient care — from consultation to disease management — in the short, medium, and long term, given what is unknown about getting the pandemic under control and the uncertainty over the time frame for COVID-19 vaccine development and approval.

Virtual Patient Consultation: Is Telehealth for Every Patient?

The need for ongoing routine care during a deadly global disease has brought new challenges to clinical practice and the need for virtual patient care via telehealth. This includes assessing clinical symptoms; evaluating the results of routine blood tests; making adjustments to medications; managing treatment side effects; and providing psychological support, patient education, and advice.

To accommodate the recommendations for social distancing and the avoidance of in-person medical consultations, the US Centers for Medicare & Medicaid Services expanded access to and relaxed the regulations for use of telehealth for medical consultations.8 While telehealth has enabled some continuum of patient care, it has also been associated with questions and uncertainties related to the approved platforms for telehealth services, state licensure requirements, commercial payer policies, and coding and billing. The American College of Rheumatology (ACR) has developed a comprehensive resource on telehealth as a guide to help physicians navigate virtual consultancy for ongoing patient care.9

Telehealth is not a new concept and has been a critical component of medical care in some parts of the world, particularly in the rural areas of low- and middle-income countries. The successful use of telemedicine for the treatment of patients with rheumatologic and musculoskeletal diseases was demonstrated in a study of more than 4800 patients in Iran who were managed remotely for longer than 5 years by a rheumatologist based in the United States.10 The most common disorders managed were osteoarthritis (23.6%), rheumatoid arthritis (13.4%), axial spondyloarthropathies (13.3%), lumbar spinal stenosis (8.8%), meniscal tear of the knee (6.7%), psoriatic arthritis (4.5%), fibromyalgia (3.5%), and lupus (0.4%).10 Disease management included diagnostic tests (serologic tests, plain radiographs, magnetic resonance imaging, bone densitometry, and electromyography and nerve conduction studies) and prescription medicines (nonsteroidal anti-inflammatory drugs, methotrexate, pregabalin, duloxetine, sulfasalazine, etanercept, tofacitinib, adalimumab, and infliximab).10

Given the trajectory of the COVID-19 pandemic, as well as the uncertainty over its duration, the latter study suggests that telehealth can be used to successfully manage patients with rheumatologic and musculoskeletal diseases on a long-term basis.11 However, a cautious note comes from Syed Atiqul Haq, MD, MBBS, FRCP, FCPS, professor of rheumatology, president of the Asia Pacific League of Associations for Rheumatology (APLAR), and vice president of the Lupus Foundation of Bangladesh. “Telehealth is appropriate for the majority [of patients but], not for all,” said Dr Haq. So, when is telehealth not appropriate? “In case of emergencies,” Dr Haq clarified, “for example, systemic lupus erythematosus (SLE) with acute breathlessness, when the need for palpation, auscultation, etc cannot be obviated by supplementary history, inspection, and investigations.” The European League Against Rheumatism (EULAR) guidelines recommend postponement of nonessential rheumatology appointments if these can be safely delayed; for essential appointments, virtual consultations should be considered. Despite the uncertainties and the evolving understanding of COVID-19, telehealth has become an essential medium for communicating accurate information and providing education and support to patients. The current advice to patients is to observe the guidelines for social distancing, masking, and regular hand washing, especially if the patients are receiving immunosuppressive therapy or have lung fibrosis.

Rules of Engagement: Treating Rheumatic and Musculoskeletal Diseases During the COVID-19 Pandemic

Immunosuppressive agents are central to the treatment of many rheumatic and musculoskeletal diseases, especially those that are driven by the uncontrolled response of the immune system that manifests as a tissue-damaging inflammatory cascade. Appropriately and optimally treating rheumatic and musculoskeletal diseases is challenged by the atypical manifestations of COVID-19 that can mimic the symptoms of rheumatic and musculoskeletal diseases and complicated by side effects from the various antiviral agents that have been used to treat COVID-19 infection.12,13 In fact, the proinflammatory cytokines induced in COVID-19 — interleukin (IK)-6, IL-1β, tumor necrosis factor (TNF), and the Janus kinase (JAK) pathway — have similarities to those targeted in the treatment of rheumatoid arthritis.14 However, the impact of the COVID-19-induced proinflammatory cytokines on rheumatic and musculoskeletal diseases is currently unknown.

In this new normal, rheumatologist and other healthcare providers treating rheumatic and musculoskeletal diseases must make critical decisions for disease management that include patient eligibility for treatment, selection of appropriate treatment, and dose management, as well as disease monitoring and treatment side effect mitigation. Healthcare providers must also consider when it is appropriate to temporarily halt treatment or discontinue therapy, particularly nonbiologic and biologic DMARDs that may be associated with increased infection risk.

The potential for an increased risk for SARS-CoV-2 infection is a serious concern for both physicians and patients. The at-risk population has been widely recognized as older people with a pre-existing condition. Severe cases of SARS-CoV-2 infection have been determined to involve potentially fatal respiratory dysfunction; therefore, SARS-CoV-2 infection is a major concern for patients with systemic sclerosis who are vulnerable to interstitial lung disease.15 Consequently, patients with rheumatic and musculoskeletal diseases, who generally fall into the “at-risk population,” are likely to be anxious about an increased risk for SARS-CoV-2 infection. Although there are currently no robust data that have assessed the risks of SARS-CoV-2 infection in specific rheumatic and musculoskeletal diseases, small-scale single-center studies suggest higher infection rates in this population.

A study of 1641 Italian patients with autoimmune systemic disease found a higher prevalence of COVID-19 disease compared with the general Italian population; prevalence among patients with connective tissue diseases (including systemic sclerosis, lupus, undifferentiated connective tissue disease, polymyositis/dermatomyositis, and Sjögren syndrome) was significantly higher compared with patients with inflammatory arthritis (including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis). A higher frequency of COVID-19 was also seen in patients who were not receiving ongoing treatment with hydroxychloroquine and methotrexate.16 Similar findings were observed in a study of hospitalized COVID-19 patients with chronic inflammatory rheumatic diseases.17 In this study, patients with connective tissue disease (but not those with inflammatory disease or those previously treated with immunosuppressive therapies) had more severe COVID-19 presentation.17 These findings suggest that hydroxychloroquine and methotrexate may have a protective role against COVID-19.

It has been generally thought that a robust immune system is essential for recovery from a SARS-CoV-2 infection. Key questions that arise are whether SARS-CoV-2 infection presents a serious challenge for immunocompromised patients with inflammatory autoimmune systemic disease and whether treatment regimens, particularly immunosuppressive medications, should be modified in dosage or temporarily discontinued. These are questions that can be answered with some degree of confidence only as studies are conducted and data emerge. However, early small-scale studies conducted in areas with a high rate of cases of COVID-19 suggested that among patients with rheumatic diseases, poor outcome and mortality were more closely associated with older age and comorbidities than with the degree of pharmacologic immunosuppression.18 Another study suggests that the incidence and severity of SARS-CoV-2 infection in patients with rheumatic diseases treated with targeted synthetic or biologic DMARDs were not significantly different from those of the general population.19

The confusion in the early days of the COVID-19 pandemic was reflected in patients’ perceived increased risk to SARS-CoV-2 infection and poor outcomes from immunosuppressive therapy. These perceptions resulted in suboptimal disease management, either from patients changing or stopping their medication schedule without consultation with their healthcare provider or from disruption to their medication due to shortages in supply, such as that seen with hydroxychloroquine.20

Guidance for the Treatment of Rheumatic and Musculoskeletal Diseases

The uncertainty over the appropriate and optimal treatment of rheumatic and musculoskeletal diseases in the setting of SARS-CoV-2 infection prompts a concerted effort for evidence-based guidance. The following guidelines have been published since April 2020 to provide a guide for the management of patients with rheumatic and musculoskeletal diseases in the setting of COVID-19:

• American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID-19 Pandemic: Version 221
• EULAR Provisional Recommendations for the Management of Rheumatic and Musculoskeletal Diseases in the Context of SARS-CoV-211
• Care for Patients With Rheumatic Diseases During COVID-19 Pandemic: A Position Statement From APLAR22
• Managing Patients With Rheumatic Diseases During the COVID-19 Pandemic: The French Society of Rheumatology Answers to Most Frequently Asked Questions Up to May 202023
• British Society of Rheumatology COVID-19 Guidance24
 
The guidelines acknowledge the organic nature of the recommendations and the need for updates as new knowledge emerges. A case in point is the guidance published by the ACR in April 202025 that was updated in July 202019 to reflect the latest evidence; future updates are anticipated. Robert B.M. Landewé, MD, PhD, professor of rheumatology at the Amsterdam Rheumatology & Clinical Immunology Center, the Netherlands, and lead author on the EULAR provisional recommendations, commented that currently much is not known regarding the treatment of patients with rheumatic and musculoskeletal diseases, including recommendations for delaying or stopping routine vaccinations. “A good question. [The] answer [is] still unknown [and] should be figured out first,” said Dr Landewé.

Challenging definitive recommendations is the lack of data, explained Jose L Pablos, MD, PhD, professor at the Universidad Complutense de Madrid (UCM), Spain. “There is no evidence of a deleterious effect of maintaining previous therapy, but most rheumatologists stop the therapy when COVID-19 is suspected or diagnosed, and therefore there is not much information on the outcomes in patients maintaining immunosuppressants.” Overall, however, the guidelines are consistent in their recommendations for the treatment of patients with rheumatic and musculoskeletal diseases. In the setting of active SARS-CoV-2 infection, treatment should be individualized to the patients’ specific needs. Patients should not stop or reduce their medication, including recommended vaccinations, unless considered necessary by the physician. Indeed, the EULAR provisional recommendations specifically caution that stopping immunosuppressant drugs could lead to a flare-up of rheumatic conditions, although evidence is still emerging about the effects of immunosuppressant drugs on COVID-19.11 On vaccination, Dr Haq agrees: “The recommended vaccines must be given to the rheumatic patients as per schedule; vaccination should not be deferred.” Dr Haq added, “Vaccinations may be deferred when a patient is infected with SARS-CoV-2 until recovery, as we are not sure about the probability of virus-mediated allergy and other consequences.”

The current general guidance is for the continuation of glucocorticoids and antimalarial (hydroxychloroquine/chloroquine) with consideration for dose reduction. According to Dr Pablos, “Glucocorticoids should not be stopped and have shown efficacy to treat COVID-19 at intermediate or high doses.” Treatment with agents including sulfasalazine, methotrexate, leflunomide, immunosuppressants, and biological agents other than IL-6 receptor inhibitors and JAK inhibitors should be stopped or withheld during active COVID-19. Treatment should resume when the patient is free of COVID-19 symptoms and at least 2 weeks after documentation of COVID-19.13,26

Although the various guidelines are consistent in their recommendations, the details and focus of each guideline vary. The most comprehensive is the guidance provided by the ACR as summarized in Table 1; the focus of the other guidelines is summarized in Table 2. The provisional guideline recommendations from EULAR specifically state that currently there are no data to support that patients with rheumatic and musculoskeletal diseases or patients treated with DMARDs have increased susceptibility to SARS-CoV-2 or have a worse prognosis if infected.11 Furthermore, although patients with systemic inflammatory rheumatic and musculoskeletal diseases are reported to be at increased risk for viral infections, there is currently no evidence that this risk is also associated with COVID-19.27

Table 1. American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID-19 Pandemic, Version 2
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Table 2. Additional Guidance on the Management of Rheumatic and Musculoskeletal Disorders During the COVID-19 Pandemic
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Given the evolving nature in the understanding of COVID-19, a few practice pearls were provided by Drs Haq, Pablos, and Landewé that may serve as a guide to practitioners:

Dr Haq:

• Heighten professional attitude, including empathy, and maintain appropriate demeanor, including paying full attention and maintaining eye-to-eye contact during teleconsultations;
• Practice evidence-based medicine strictly, and exercise due caution in prescribing immunosuppressive medicines, with particular emphasis on exclusion of infections;
• Give due emphasis on evidence-based nonpharmacologic treatment options.

Dr Pablos:

• It is important to maintain contact with patients who are receiving treatment and reassure them that it is not advisable to withdraw [treatment] preventively;
• In the case of suspected or diagnosed COVID-19, provide patients with instructions on what to do with the usual treatment;
• There does not seem to be a greater risk of severe COVID-19 in patients with chronic arthritis, whereas the risk doubles in patients with systemic autoimmune diseases and, therefore, this group should take extreme protective measures.

Dr Landewé:

• Advise patients not to stop their antirheumatic treatment, to practice social distancing, and to consult their rheumatologist.

References

1. United States COVID-19 cases and deaths by state. Centers for Disease Control and Prevention website. https://covid.cdc.gov/covid-data-tracker/#cases_totaldeaths. Updated September 24, 2020. Accessed September 24, 2020.
2. COVID-19 hospitalization and death by age. Centers for Disease Control and Prevention website. https://www.cdc.gov/coronavirus/2019-ncov/downloads/covid-data/hospitalization-death-by-age.pdf. Updated September 24, 2020. Accessed September 24, 2020.
3. Worldometer. COVID-19 Coronavirus Pandemic. https://www.worldometers.info/coronavirus/. Updated September 17, 2020. Accessed September 17, 2020.
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8. Medicare Telemedicine Health Care Provider Fact Sheet. CMS.gov. https://www.cms.gov/newsroom/fact-sheets/medicare-telemedicine-health-care-provider-fact-sheet. Accessed September 17, 2020.
9. COVID-19 Practice and Advocacy Resources. American College of Rheumatology. https://www.rheumatology.org/Announcements/COVID-19-Practice-and-Advocacy. Updated September 11, 2020. Accessed September 17, 2020.
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15. Orlandi M, Lepri G, Bruni C, et al. The systemic sclerosis patient in the COVID-19 era: the challenging crossroad between immunosuppression, differential diagnosis and long-term psychological distress. Clin Rheumatol. 2020;39(7):2043-2047. doi:10.1007/s10067-020-05193-2
16. Ferri C, Giuggioli D, Raimondo V, et al. COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series. Clin Rheumatol. Published online Aug 27, 2020. doi:10.1007/s10067-020-05334-7
17. Pablos JL, Galindo M, Carmona L, et al. Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort studyAnn Rheum Dis. Published online Aug 12, 2020. doi:10.1136/annrheumdis-2020-218296
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19. Favalli EG, Monti S, Ingegnoli F, Balduzzi S, Caporali R, Montecucco C. Incidence of COVID-19 in patients with rheumatic diseases treated with targeted immunosuppressive drugs: what can we learn from observational data? Arthritis Rheumatol. Published online June 7, 2020. doi:10.1002/art.41388
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22. Tam LS, Tanaka Y, Handa R, et al. Care for patients with rheumatic diseases during COVID-19 pandemic: a position statement from APLAR. Int J Rheum Dis. 2020;23(6):717-722. doi:10.1111/1756-185X.13863
23. Richez C, Flipo RM, Berenbaum F, et al. Managing patients with rheumatic diseases during the COVID-19 pandemic: the French Society of Rheumatology answers to most frequently asked questions up to May 2020. Joint Bone Spine. Published online May 27, 2020. doi:10.1016/j.jbspin.2020.05.006
24. COVID-19 guidance. British Society of Rheumatology. https://www.rheumatology.org.uk/practice-quality/covid-19-guidance. Updated July 29, 2020. Accessed September 17, 2020.
25. Mikuls TR, Johnson SR, Fraenkel L, et al. American College of Rheumatology guidance for the management of rheumatic disease in adult patients during the COVID-19 pandemic: version 1. Arthritis Rheumatol. Published online Apr 29, 2020. doi:10.1002/art.41301
26. Kow CS, Hasan SS. Pharmacotherapeutic considerations for systemic rheumatic diseases amid the COVID-19 pandemic: more questions than answers. Drugs Ther Perspect. Published online Aug 16, 2020. doi:10.1007/s40267-020-00767-1
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Reviewed October 2020