key: cord-309026-l2rh9bie
authors: Sweiss, Nadera J.; Korsten, Peter; Syed, Huzaefah; Syed, Aamer; Baughman, Robert P.; Yee, Arthur M.F.; Culver, Daniel A.; Sosenko, Teresa; Azuma, Arata; Bonella, Francesco; Costabel, Ulrich; Drake, Wonder P.; Drent, Marjolein; Lower, Elyse E.; Israel-Biet, Dominique; Mostard, Remy LM.; Nunes, Hilario; Rottoli, Paola; Spagnolo, Paolo; Wells, Athol U.; Wuyts, Wim A.; Judson, Marc A.
title: When the game changes: Guidance to adjust sarcoidosis management during the COVID-19 pandemic
date: 2020-04-29
journal: Chest
DOI: 10.1016/j.chest.2020.04.033
sha: 
doc_id: 309026
cord_uid: l2rh9bie

nan

Over the past few months, the novel coronavirus disease (COVID-19) pandemic has posed many challenges for practicing phyicians.Sarcoidosis patients may have an increased risk of a poor outcome and death from COVID-19 infection for several reasons. First, sarcoidosis involves the lung in approximately 90% of patients, 1 many of whom have diminished baseline lung function with reduced pulmonary reserve should they develop respiratory failure. Second, although the etiology of sarcoidosis is unknown, it is postulated that immunologic dysfunction and dysregulation play essential roles in the development of the disease. 2 Third, African-American race and many comorbidities associated with glucocorticoid (GC) therapies such as hypertension, diabetes, and obesity have been identified by the Centers for Disease Control as independent risk factors for COVID-19-related death and are more prevalent in sarcoidosis cohorts. 3 Finally, and most pertinent to the treating clinician, immunosuppressive medications are the primary agents used for the treatment of sarcoidosis, particularly GCs, which are often the first line agent. 4 Little is known about the impact of sarcoidosis treatments on susceptibility to and disease expression of COVID-19 infection; however, because of the lethality of COVID-19 infection, there is concern that the risk-benefit ratio of effective immunosuppressive therapies for sarcoidosis may be altered in the current climate. In this document, we aim to provide clinicians with practical guidance on how to adjust immunosuppressive therapy for the treatment of sarcoidosis during the COVID-19 pandemic. This guidance Many of the immunosuppressive agents used to treat sarcoidosis are used in rheumatic diseases. Based on systematic reviews and meta-analyses, it is known that these drugs, notably systemic GC and biological agents (such as TNF inhibitors), increase the risk for serious infections. 5, 6 Traditional steroid-sparing agents, most importantly methotrexate (MTX), are also associated with an increased risk of infection, but the degree of risk depends on the nature of the underlying illness, dosage, treatment duration and infection in question, 7 and is generally considered to be lower than that with GC and biologic agents. 7, 8 Although lowering immunosuppression might improve the outcome of a sarcoidosis patient who becomes exposed to COVID-19, it is also associated with the risk of worsening sarcoidosis. In practice, treating physicians are confronted with two general scenarios: first, a patient who is clinically quiescent maintained on a stable medical regimen; or second, a patient with active, organ-threatening disease.

If a stable sarcoidosis patient is receiving GC therapy alone, an attempt can be made in most cases to slowly reduce the corticosteroid dose. Notably, in a randomized trial with GC tapering, a high proportion of patients treated with placebo was successfully able to taper prednisone dosage by more than 50% without flares of the disease over several months. 8 In one study of 36 patients with pulmonary sarcoidosis who had a pulmonary exacerbation, none were receiving more than 10 mg/day of prednisone at the time of their exacerbation. 9 Even exacerbations of pulmonary disease usually do not result in significant respiratory distress and usually respond to modest increases in corticosteroid dosages for just a few weeks. 9 Skin sarcoidosis is a specific, non-life-threatening form of the disease where it may be prudent to attempt to taper therapy.

In stable patients who are currently on disease-modifying anti-sarcoid drugs (DMASDs), such as MTX, mycophenolate mofetil, azathioprine, and others, de-escalation of therapy should be considered. This can be achieved by reducing the dose or prolonging the dosing interval. For example, if a patient is stable on weekly MTX, a dose reduction or dosing every other week instead of every week are reasonable options. An outright drug holiday for several weeks, while risk-benefit is continually reassessed, may be considered for some patients, but this could increase the chance for more abrupt sarcoidosis flares that may be more refractory to control and prompt additional GC therapy. It is re-emphasized that DMASDs may present lower risk of infections than GC.

In patients who are receiving antimalarial agents, such as chloroquine or hydroxychloroquine (HCQ), we suggest continuing therapy. Unfortunately, because of preliminary inconclusive reports suggesting a potential benefit of HCQ in the treatment of COVID-19, 10 widespread shortages have ensued.

Patients who receive immunosuppressive biologic agents may be at increased risk of COVID-19 infection. However, because of concern for rebound sarcoidosis flares, which may be problematic to control if these medications are discontinued abruptly, a gradual dose reduction could be considered. For example, infliximab (IFX) may be given less frequently (e.g., every six to eight weeks instead of monthly), or at a lower weight-based dose (e.g., 3 mg/kg instead of 5 mg/kg of body weight). In addition, premedication with GC could be reduced significantly or eliminated from the infusion protocol. When DMASDs are used for prevention of antibody formation in patients on TNF inhibitors, a low dose (e.g., methotrexate 10 mg weekly) is considered effective. 11 If immunosuppression is reduced, clinicians should instruct the sarcoidosis patient to be vigilant for any changes in their condition that are suggestive of active disease. The clinician should establish facile methods of communication with their patients including rapid consultation systems (such as telemedicine) and other appropriate safeguards.

In sarcoidosis patients with organ or life-threatening disease, a significant dose reduction or discontinuation of therapy may be contraindicated because of the risk of severe unfavorable outcomes. Such patients include those with progressive pulmonary disease, cardiac disease, uveitis, or neurosarcoidosis.

Patients who are on GC therapy alone should be managed with the lowest possible dose to achieve disease control. If very high-doses of GC (e.g., >40-60 mg of prednisone per day) are necessary, the addition of a DMASD may be prudent to enable a reduction of GC requirements, since GC therapy is associated with a high risk of infection in sarcoidosis patients. 12 Such patients who have been stabilized on DMASDs should probably be maintained on current dosages. In patients with biologic therapies, such as IFX and adalimumab (ADA), therapy also should probably be continued because of the consequences of disease relapse. Due to logistic concerns (such as potential closure of infusion units), switching to home infusion of IFX or to subcutaneous ADA may be considered in carefully selected patients. In patients with active disease who cannot receive biologic therapies for logistic or clinical reasons, alternative treatments, such as tofacitinib, repository corticotropin, or others, may be considered on a case by case basis. However, convincing evidence of their efficacy in severe disease from clinical trials is not yet available.

We also suggest that the assessment of symptoms in sarcoidosis patients involve the judicious use of objective testing such as pulmonary function tests and chest imaging to avoid unnecessary evaluations in the clinic and hospital. Again, this is a standard practice that we emphasize during this pandemic. The correlations between flares of sarcoidosis and changes in pulmonary function and chest imaging are known to be poor, and the determination of whether a sarcoidosis patient is developing worsening disease may often be made on clinical grounds alone.

In conclusion, sarcoidosis management during the current COVID-19 pandemic poses many challenges for treating physicians. We have offered a generalized approach to this issue (Figure 1) . The risk of a poor outcome from COVID-19 infection must be factored into the clinician's treatment algorithm. This may result in an adjustment of the sarcoidosis patient's immunosuppressive regimen depending on the stability of their disease and consequences of disease reactivation. If immunosuppression is reduced, a clear-cut plan to monitor and treat exacerbations of sarcoidosis should be in place. We acknowledge that our understanding of COVID-19 infection is currently meager and expect that more evidence-based recommendations will be developed over time.

Treating physicians should remain vigilant to the changing landscape of the available COVID-19 testing, the high variability in local and regional prevalence of the virus and the evolving COVID-19 treatments in their decision making. 

Clinical characteristics of patients in a case control study of sarcoidosis

Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 -COVID-NET, 14 States

Corticosteroids in Sarcoidosis

Predictors of infection in rheumatoid arthritis

Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and metaanalysis

Risk of Infection with Methotrexate Therapy in Inflammatory Diseases: A Systematic Review and Meta-Analysis

Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis

Efficacy of short-course, low-dose corticosteroid therapy for acute pulmonary sarcoidosis exacerbations

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice

Fungal infections as a complication of therapy for sarcoidosis