How Immunosuppression May Affect COVID-19 Vaccine Response

Although we can expect to learn much more, preliminary data are now available on the potential safety and effectiveness of COVID-19 vaccines in rheumatology patients. The picture is likely to be nuanced, with not all types of immuno­suppressive treatments having identical impacts on vaccine response.

Rheumatologists should use caution in interpreting early reports, while continuing to encourage their patients to get vaccinated and take appropriate preventative measures.

Immunosuppressed Patients

The large trials used to test the efficacy and safety of the SARS-CoV-2 messenger RNA (mRNA) vaccines largely excluded patients with rheumatic diseases, as well as people on immunosuppressives for other indications. Although this made sense in terms of vaccine development, it left open questions about the efficacy and safety of the vaccines for people taking immunosuppressive therapies. Such individuals may potentially be at risk of a poor response to one or more of these vaccines, in terms of decreased efficacy or due to potential side effects, such as disease flare.

Dr. Segev

Dorry L. Segev, MD, PhD, a professor of surgery and epidemiology at Johns Hopkins School of Medicine, Baltimore, is an investigator on two ongoing trials focused on these responses. In one trial, researchers are studying immunosuppressed solid organ transplant recipients, and in another they are looking at vaccine responses in people with chronic conditions that require immunosuppression, including rheumatic diseases.

Because of the very nature of immunosuppressive medications, researchers have held concerns about whether people taking such medications will form an adequate long-term immune response when vaccinated. According to Dr. Segev, to respond effectively to a vaccine, the immune system must successfully activate certain pathways involving antigen presentation, potentially evoking both a B cell and T cell response. “Medications that suppress the immune system might suppress certain parts of that pathway, and some might suppress parts of it more than others,” he says.

To provide guidance to rheumatologists with respect to the new COVID-19 vaccines, the ACR convened a COVID-19 Vaccine Guidance Task Force, a branch of the broader ACR vaccine guideline effort. To make their recommendations, members of the task force surveyed the available literature on COVID-19 and COVID-19 vaccines, as well as indirect data on the response to other types of vaccines in patients with rheumatic conditions.¹

One task force member, Cassandra Calabrese, DO, a rheumatologist and infectious disease specialist who is an associate staff member at the Cleveland Clinic, Ohio, notes that although people often group immunosuppressed patients together, patients receiving different specific types and degrees of immunosuppression may respond quite differently in terms of vaccine reactogenicity.

For example, a 2014 meta-analysis concluded patients receiving rituximab displayed a poorer humoral response to both the influenza and pneumococcal vaccines, but patients on tumor necrosis factor (TNF) inhibitors did not show reduced response to either vaccine.²

Making use of the data available, the task force made specific recommendations about vaccination timing and immunomodulatory therapy for specific treatments. These included scheduling the vaccine to be given about four weeks prior to the next scheduled rituximab cycle and delaying rituximab two to four weeks after the second vaccine dose, if patient circumstances permit.¹

The committee has released an updated version of its vaccine guidance, based on the initial data about vaccine response that have begun to accrue.³ This version provides updated recommendations on timing considerations for mycophenolate mofetil, methotrexate, acetaminophen and non-steroidal anti-inflammatory drugs. (The full second version of the paper is expected to be published in Arthritis & Rheumatology.)