Issue: November 2021
Disclosures: Calabrese reports consulting relationships with AbbVie, Centecor Biopharmaceutical, Crescendo Bioscience, GlaxoSmithKline, Horizon Pharma, Janssen Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals and UCB.
November 18, 2021
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Outpatient COVID-19 management: Do your immunosuppressed patients know who to call?

Issue: November 2021
Disclosures: Calabrese reports consulting relationships with AbbVie, Centecor Biopharmaceutical, Crescendo Bioscience, GlaxoSmithKline, Horizon Pharma, Janssen Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals and UCB.
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First, let me say that I clearly do not know how the pandemic will end, but after considerable and ongoing study of this question, I am convinced it will not magically disappear.

Most COVID-19 pundits suspect that it will continue to circulate in some form and that the fortunate among us who are vaccinated, boosted and have good immune responses will be largely protected with some suffering mostly mild to moderate infections. If so, it’s mostly good news, and while things will be different, they will assume some approximation of normal for most of us.

Leonard H. Calabrese, DO
Leonard H. Calabrese

Unfortunately, we as rheumatologists, along with many other colleagues who care for the approximately 3% of the population with compromised immune systems (ie, IBD, immune mediated skin diseases, multiple sclerosis, transplantation, oncology, primary and secondary immunodeficiency states), will face a different future.

We, as a collective, will be challenged as we try to appraise who among our patients are unlikely to have mounted a meaningful response to our vaccines, including boosters, and develop strategies to both educate our patients and develop care pathways providing the best available therapies to treat and prevent infections with SARS-CoV-2.

Implicit in this vison will be reliable biomarkers to identify such at-risk individuals and the development of new outpatient therapies, including oral or inhaled antivirals (one such agent, molnupiravir, is currently undergoing regulatory approval evaluation), immune-boosting therapies (none currently available but many in advanced stages of evaluation) and monoclonal antibodies (current and next generation) of which we currently have three different agents in the U.S. with emergency use authorization and a fourth undergoing regulatory approval evaluation as I write this.

Focusing on the monoclonal landscape, as this is currently our most potent weapon for early disease, I see several challenges and opportunities. First, of the three available agents for treatment, all have demonstrable efficacy for significantly reducing the likelihood of hospitalization and disease progression if given early, and have held up relatively well to current variants. In fact, they carry a 10-day window from onset of symptoms to treatment in their EUA labeling and thus prompt diagnosis and recognition of who is a high-risk patient; thus, eligibility is critical. This must then be followed by prompt referral for therapy.

There are data that these agents may also be effective for hospitalized patients who have been unable to mount a serologic response, but that is not what I am focusing on. To do this right requires educated patients who are aware that they are vulnerable and have a strategy to enter the care pathway leading to treatment. I have already seen such patients call their primary care provider, who may be well-meaning but possibly unaware of the risks or uninformed about how to get the treatment.

I have asked many practitioners how they do it and have found a wide range of both declarative and procedural knowledge among our colleagues; I even conducted a Twitter poll last month and the results weren’t promising, with most uncertain of how to proceed. In some areas, large medical centers are well-organized and efficient; in others, not so much.

Furthermore, many infusion centers have stepped up and developed high-efficiency care pathways, but it’s all regional. Ask yourself: Who is doing it right in your area? Pharmaceutical companies that make these agents should be providing patient education and provider education in a fast and furious fashion as pandemics don’t wait for calendar years to get things done.

Finally, let me also remind you that there is also an EUA for REGEN-COV (casirivimab/imdevimab, Regeneron) for post-exposure prophylaxis. This indication refers to the scenario where an individual at high risk (ie, unvaccinated or unlikely to have responded to vaccination) has a high-risk exposure, such as an infected member of the household or prolonged exposure to an infected individual in close quarters. For these patients, prompt treatment with monoclonals dramatically reduces the likelihood of infection.

Consider our most vulnerable patients, namely those on B-cell depleting monoclonal antibodies or on high-dose glucocorticoids and other agents such as cyclophosphamide and mycophenolate among others; for many of these patients, this could be lifesaving.

Additionally, the new monoclonal AZD7442, a combination of two long-acting antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061) from AstraZeneca, is energizing the field and currently under EUA evaluation for prophylaxis. If approved, we can then manage our most vulnerable patients with ongoing intramuscular therapy, perhaps at 6-month intervals in a similar way as IVIG in patients with humoral immunodeficiency states. I have discussed this possibility with a number of patients and the interest is extremely high as many feel like prisoners in a bad movie when they compare themselves to their fully-vaccinated friends and family.

To see this outpatient care pathway optimized will require more reliable biomarkers of vulnerability and numerous studies are underway to provide such. For now, I will tell you that I am testing all my most highly immunosuppressed patients for anti-spike antibodies despite the lack of endorsement for such testing by regulatory agencies.

I will categorically state in my view, failure to make any detectable anti-spike antibody is a biomarker of profound vulnerability, regardless of cell-mediated responses for which we now have no clinical correlates for protection. In these patients, I am vigorously educating about what to do if exposed or infected. In the future, they will be first in line for preexposure prophylaxis (PreP) when available. Get ready for the next wave.

Do you have a plan in place? Tell me yours at calabrl@ccf.org or at rheumatology@healio.com.