'No need' to suspend immunosuppressive drugs due to COVID-19: No impact on risk outcomes
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It is only natural that individuals taking immunosuppressive medications would fear COVID-19.
However, recent findings add to a growing body of data indicating that immunosuppression may not elevate risk for worse outcomes for COVID-19 hospitalization.
The fears surrounding immunosuppression and COVID-19 are twofold. One concern is that these drugs would elevate risk of acquiring the virus. The other is that these drugs would lead to more severe complications upon infection.
Kayte Andersen, MSc, a PhD candidate in the Johns Hopkins Bloomberg School’s Department of Epidemiology, and colleagues aimed to answer the second question.
They conducted a retrospective cohort study in 2,121 consecutive adult patients admitted to the Johns Hopkins Medicine health system with a confirmed or suspected diagnosis of COVID-19 between March 4, 2020, and Aug. 29, 2020.
Results published in Clinical Infectious Diseases showed that 5% of this group was immunosuppressed prior to COVID-19 diagnosis. Prednisone, tacrolimus and mycophenolate mofetil were the most commonly reported immunosuppressive medications.
Adjusted analysis findings did not find a significant increase with regard to in-hospital mortality among immunosuppressed versus non-immunosuppressed patients (HR = 0.66; 95% CI, .28–1.55). Similarly, immunosuppression did not elevate risk for mechanical ventilation (HR = 0.79; 95% CI, .46–1.35) or length of stay (HR = 1.16; 95% CI, .92–1.47).
Healio Rheumatology sat down with Andersen and G. Caleb Alexander, MD, MS, of the Johns Hopkins Bloomberg School of Public Health and Center for Drug Safety and Effectiveness, to discuss the rationale behind the study, the encouraging nature of the findings and the next steps for research.
Healio: What prompted the study?
Andersen: This is a really important question. Immunosuppressed people have been identified as high-risk for COVID-19 by the CDC.
Alexander: There was some concern at the outset of the pandemic that patients were discontinuing immunosuppressive medications due to fear of acquiring COVID-19 or experiencing worse outcomes if they acquired the virus.
Healio: Was the cohort defined by immunocompromised state due to disease or medications?
Andersen: The cohort was all people hospitalized with COVID-19 at the five Johns Hopkins hospitals. We defined people as being immunosuppressed or not by their medications, which were often drugs for patients with rheumatic or autoimmune diseases, as well as solid organ transplant. Altogether, this group comprised 5% of our cohort.
Alexander: This was primarily a study for patients being treated with immunosuppressive medications. That was how we derived the cohort and that was the exposure of interest.
Healio: There was no difference in risk of mechanical ventilation, in-hospital mortality or length of stay. Did age, gender or specific disease impact the results?
Andersen: We were able to account for age, gender and health conditions before they were admitted to the hospital with COVID-19. We still found no difference in outcomes, which we found reassuring. We were not able to look, in this study, at specific drug classes or drugs. But we plan to do that moving forward in a larger data set.
Healio: To what extent, and why, are you encouraged by these results?
Alexander: The study contributes to a growing body of evidence showing that individuals taking chronic immunosuppressive medications do not fare worse than their counterparts in terms of COVID outcomes. Looking at the big picture, one of the most encouraging aspects of these results is that this is a small amount of good news at a time in this pandemic when we need it. Doctors and patients may have been deciding to discontinue these medications to this point. We are starting to see that there is no need for this. Our work continues to be corroborated by other studies showing similar outcomes.
Healio: Not to undermine the encouraging nature of the data, but one thing we have seen throughout this pandemic is that the evidence supporting or opposing any given conclusion can change in a short period of time. Are there any concerns further evidence may show that the picture is more complicated than it seems at the moment?
Andersen: At the moment, our evidence is consistent with what we are seeing from other groups in the literature.
Alexander: That said, I do not think our findings amount to a blank check to go out and get started on immunosuppressive medications without careful consideration. But the fact remains that many people need these drugs, because of an organ transplant or because they have an autoimmune or rheumatic disease. What our findings show is that these drugs were not associated with worse outcomes from COVID, which we think is an important conclusion.
Healio: Are there any concerns about drug-drug interactions between immunosuppressive medications and either the antivirals being used to treat COVID-19 or dexamethasone?
Andersen: We plan to look at that in the national data set. We want to see if patients coming into the hospital on immunosuppression are perhaps treated differently, given that dexamethasone is one of the mainstays of treatment at this moment. That is a question that is ongoing.
Healio: Looking ahead, what are the next steps for your group?
Andersen: We have been working in a national data set called the N3C, or the National COVID Cohort Collaborative, which is a national collaboration of more than 30 hospital systems across the United States. We are looking at outcomes for immunosuppressed patients in a national cohort, to see if we would see the same result.
We hope to look at the same clinical questions we addressed in this study and more. Primarily, though, we will be focusing on those two main groups of patients on immunosuppressive medications: solid organ transplant recipients and those with autoimmune or rheumatic diseases.
Alexander: As with any study, ours raises as many questions as it answers. In our study, we combined all of the immunosuppressive medications. The sample size did not allow us to really look at individual drugs in great detail, or those that operate with different mechanisms of action. The pharmacology of many immunosuppressive drugs differs greatly. So, we think that it will be important in future work to explore some of these questions in the context of COVID outcomes.
There is an enormous urgency to answer these questions because the pandemic has never been worse. We need to continue the effort to generate fundamental new knowledge. Fortunately, there are legions of scientists around the world that are working to do so.
For more information:
G. Caleb Alexander, MD, MS, and Kayte Andersen, MSc, can be reached at 615 N. Wolfe Street, W6035; email: galexand@jhsph.edu.
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