Issue: June 2022
Disclosures: Calabrese reports professional relationships with AstraZeneca, Bristol Myers Squibb, AbbVie, Genentech, Janssen, Galvani, GlaxoSmithKline, UCB, Sanofi, Regeneron and Novartis.
June 21, 2022
3 min read

Safety in rheumatology, COVID-19 and Evusheld PreP: Where do you stand?

Issue: June 2022
Disclosures: Calabrese reports professional relationships with AstraZeneca, Bristol Myers Squibb, AbbVie, Genentech, Janssen, Galvani, GlaxoSmithKline, UCB, Sanofi, Regeneron and Novartis.
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

This month’s cover story features an illustrious faculty — Christina Charles-Schoeman, MD, MS; Kathryn Dao, MD; Roy Fleischmann, MD; Jon T. Giles, MD, MPH; and Grace C. Wright, MD, PhD — and highlights the evolution of safety in our field, a phenomenon profoundly influenced by our rich armamentarium of targeted therapies not even dreamed of when I started training.

Treatments for rheumatic diseases a generation ago were nearly devoid of concerns for opportunistic infections. This changed when cyclophosphamide was introduced as standard of care for what we now know as ANCA-associated vasculitis. Fast forward 2 decades later and you have a snapshot of how our view and concern for safety, at least regarding infectious diseases, has evolved.

Leonard H. Calabrese, DO
Leonard H. Calabrese

From the risk for tuberculosis and hepatitis B reactivation with TNF inhibitors, to the risk for shingles with modern Janus kinase inhibitors and anifrolumab (Saphnelo, AstraZeneca), our understanding of the complicated risk/benefit ratios for targeted therapies has required constant vigilance and reevaluation. For a 30,000-foot view of this evolution, please read our recent perspective in Frontiers in Medicine.

Additionally, we now have a new dimension contributing to the evolution of safety, which comes in the form of COVID-19. I will oversimplify the field by saying that we are grateful that the vast majority of our patients with immune-mediated inflammatory diseases (IMIDs) do quite well dealing with COVID-19, after adjusting for traditional risk factors.

The glaring exception to this observation are our patients on B-cell depleting therapies (BCDTs), which in rheumatology is rituximab (Rituxan, Genentech). Study after study has demonstrated that our patients on BCDTs are exceptionally vulnerable to poor outcomes with our reported experience across the IMID spectrum, demonstrating that nearly 40% of such patients require hospitalization and 8% succumb to the infection.

This is both heartbreaking and a call to arms. Although there is a lot of exciting immunology which belies this phenomenon, the real question for the moment is what can and what are we doing about it.

I recently gave a talk at the incredible Congress of Clinical Rheumatology East, where I said plainly that we believe that all patients on rituximab should and must be on pre-exposure prophylaxis (PreP) with the monoclonal antibodies tixagevimab and cilgavimab — packaged together and branded as Evusheld (AstraZeneca).

Although PreP is not a substitute for vaccination, and we do not have extensive data on the efficacy in this specific setting, it makes total sense to administer this agent until we know otherwise. I was truly surprised at how many smart rheumatologists came up to me at the meeting and expressed a lack of awareness and knowledge, as well as a general confusion, as to how to get this done.

We strongly believe in this strategy, and at the Cleveland Clinic, under the direction of Cassandra Calabrese, DO, we are making every effort to get all of our patients using BCDTs on this preventative therapy. For a more robust discussion of the issue, including risk assessment, please read our pre-peer reviewed draft manuscript in medRxiv.

For now, ask yourself: “Of my patients who have been treated with rituximab since the beginning of the pandemic, how many are on PreP?” If the answer is not “nearly all,” then please reassess. We have been talking to many of the leaders in the rheumatology COVID-19 world and there is broad agreement on how important PreP is for this subpopulation of our patents. We also have been talking to Jack Cush, MD, one of the strongest voices in our profession, and we are mutually committed to pressing this point and providing the needed declarative and procedural education to build confidence in our community and get our patients protected now.

That’s my take — please share your PreP experience, including breakthroughs, with me at or at


Calabrese LH, Calabrese C, Lenfant T, Kirchner E and Strand V. Infections in the era of targeted therapies: mapping the road ahead. Frontiers in Medicine Rheumatology 2020 August 18;7

Calabrese, C, Kirchner, E, Husni, E, Moss, B, Fernadez A, Jin D, Calabrese, L Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy. medRxiv. doi: 10.1101/2022.02.21.22271289.

For more information:

Leonard H. Calabrese, DO, is the Chief Medical Editor, Healio Rheumatology, and Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic.