By James T. Rosenbaum, MD and Marcia A. Friedman, MD
Oregon Health & Science University
Drs. Rosenbaum and Friedman caution all readers that these guidelines are subject to change and that some of the guidelines are subject to interpretation by medical professionals.
The COVID-19 pandemic, and the ever-evolving guidelines for vaccination and treatment, have created some confusion for patients as well as for health care providers. Physicians, nurses, and other health personnel play crucial roles in managing this disease and caring for patients. The timely rollout of effective vaccines and antiviral medications is a tribute to modern science, and illustrates how far we’ve come since the 1918 flu pandemic. Despite these triumphs, we recognize that the medical community’s understanding of the virus is evolving day to day, and often, that the advice you receive will be based on the best possible assessment at a given time, which means that it might change tomorrow. Furthermore, recommendations vary from country to country, and often from state to state. And the availability of certain treatments can often confound the recommendations.
There is very encouraging news for patients with spondyloarthritis (SpA). A study published in November, 2021 (Raiker and colleagues, Clinical Rheumatology) looked at nearly 10,000 patients with COVID-19 and axial spondyloarthritis and compared them to others with COVID-19 but without SpA. The SpA patients had lower rates of mortality, less severe disease, and less likelihood of hospitalization from COVID. Of course, we do not yet know why these patients had better outcomes. It may be related to underlying immune changes or to medications used to treat SpA, or perhaps a difference in the COVID-19-related care these SpA patients received compared to non-SpA patients. Regardless of the mechanism, the results are certainly encouraging. Our own smaller survey study, sponsored by the SAA and based on responses from SAA members (Rosenbaum et al., Journal of Rheumatology, February, 2022), has also provided reassuring data about how SpA and its treatment might affect the severity of COVID-19.
The emergence of new strains like Omicron adds to the complexity of treatment recommendations. For example, some individuals are considering receiving a fourth vaccine. This is frequently done in Israel, but the benefits have been only slight. And newer vaccines could be more effective for these emerging variants. Some cautious waiting may bean option for those who already have received a booster.
Below, we do our best to provide answers to some of your most pressing questions about the current vaccine recommendations and the new antiviral medications that were recently approved.
There has been some confusion over how many vaccines those who are immunocompromised should receive. What is the CDC currently recommending? How many shots, total, should there be for immunocompromised individuals who received an mRNA vaccine? In what order should people get them, and how far apart should each be spaced?
The CDC currently recommends that moderately to severely immunocompromised patients who received mRNA vaccines initially (Pfizer or Moderna) receive a third primary dose of the vaccine at least 28 days after the first two vaccines. This is different from a booster shot. The booster dose is a single mRNA vaccine, given at least three months after the primary series for those who are immunocompromised. We strongly recommend this booster dose. For immunocompromised patients vaccinated with mRNA vaccines, they may receive up to four doses in total (three in the primary series and one booster). See the CDC’s latest updates here. *Update: On March 29, 2022, the FDA authorized an additional second booster dose for adults age 50 and over and those who are immunocompromised, given four months after the first booster dose. We will continue to update this article as more information is released.
However, there are some complicating factors. While we agree with the recommendation for a third primary dose, most of our patients have already had a two-dose mRNA primary series and a booster. The guidelines for this scenario are not yet clear.
Further, while many patients with SpA are immunosuppressed, they are rarely as immunosuppressed as, say, a patient receiving chemotherapy, a patient with HIV, or a patient with an organ transplant. It would be practically impossible for the CDC to make recommendations specific to every patient population and every immunosuppressive medication; these guidelines should ideally be used in the context of a discussion between an individual and their health care provider.
Are individuals with spondyloarthritis immunocompromised, and thus, do they automatically qualify for this third primary vaccine?
The CDC definition of “moderately to severely immunocompromised” includes anyone taking a biologic medication (such as a TNF or IL-17 inhibitor), or a medication like methotrexate. Thus, this would apply to many SpA patients. (SpA itself rarely makes a patient immunocompromised, but many of the medications used to treat SpA are immunocompromising.)
However, the CDC category of moderately to severely immunosuppressed individuals is very broad. Certainly, a patient with an organ transplant, on chemotherapy, or with HIV has different risks compared to a patient with SpA on a biologic. Secondly, while immunosuppressive medications generally reduce vaccine response, not all immunosuppressive medications impact vaccines to the same degree. Among the drugs used to treated SpA, tofacitinib (Xeljanz) and methotrexate have the most significant impact on vaccine response, while biologics like TNF, IL-23 and IL-17 inhibitors have a smaller impact, if any, on vaccine response. For this reason, while patients taking any of these medications are candidates for a third primary vaccine per the CDC, we recommend making an individual decision about this after speaking with your health care provider.
What is recommended for immunocompromised individuals who received a Johnson & Johnson primary vaccine? Should they receive an additional primary shot? What about a booster shot – and should the booster be Johnson &Johnson, or an mRNA booster?
The CDC now recommends that immunocompromised patients who received the Johnson &Johnson vaccine initially should receive an additional primary series dose using one of the two mRNA vaccines. This additional, second vaccine should be given at least 28 days after the J&J shot. These patients should also then receive a booster with the Pfizer or Moderna vaccine (not J&J), two months after their two primary vaccines, for a total of three shots.
Which medications used to treat various forms of SpA impact the immune system enough to require an extra vaccine dose?
The CDC includes all patients on immunosuppressive medications in this category—this includes all biologics (TNF, IL-17, IL-23), JAK-inhibitors, methotrexate, prednisone >20 mg/day, and any other immunosuppressive medication. However, as we note above, this category is very broad and not all immunosuppressive medications substantially impact vaccine response. Patients taking these medications should discuss their individual medications with their providers before deciding whether to get the extra primary series dose.
The ACR recently updated its vaccine clinical guidance for those with rheumatic diseases. What should the SpA community know that is new and important in this update?
The guidance is useful because it discusses how to adjust the dosage of your specific medication to improve the likelihood of mounting a strong immune system response to the vaccine. The new version also notes some of the monoclonal antibodies that are no longer recommended because they are ineffective against the Omicron variant.
Should people consider getting an antibody test to determine the need or appropriateness of a booster shot?
This is officially discouraged because interpreting the results is not straightforward. Rituximab is a biologic that is rarely prescribed for SpA. It can markedly affect the antibody response and we have occasionally requested a measurement of antibodies to COVID-19 in blood if a patient has been treated with rituximab. Overall, antibody measurements are not necessary to determine vaccination recommendations; this depends on a patient’s medication use and risk factors, not antibody measurements.
What is the protocol for someone who did not get the third shot in the primary series (even though they were qualified to), and has already gotten a booster shot? Should this person still receive an additional primary vaccine dose after the booster?
We do not yet know. Neither the CDC guidelines nor the American College of Rheumatology guidelines have clearly answered this question. We hope this will become clearer in the near future, as many of our patients face this exact circumstance.
If someone has tried to get their extra primary vaccine dose and been turned away – told by the pharmacy, for example, that they are not giving out extra doses – what should they do?
They should contact their rheumatologist or primary care physician as this pharmacist may be misinformed. The CDC does recommend that immunocompromised patients receive a third primary mRNA vaccine dose.
Antiviral Pills and Other Treatment Questions:
Two new antiviral pill regimens were recently approved – Paxlovid and molnupiravir. Can you please explain how these medications work and what they do?
These drugs interfere with the virus’ ability to replicate by blocking an enzyme that the virus needs. The pills are given twice per day for five days.
Who is qualified, and should get prescriptions for, these anti-COVID pills? What is the timeline for these medications, so they are most effective?
Patients who have a confirmed case of mild to moderate COVID-19 and who have had symptoms for less than five days are eligible if they receive immune-modulatory medications or if they have a risk factor for severe disease like being over the age of 65, lung disease, or diabetes. The two drugs differ a bit in terms of efficacy, recommendations in children, and contraindications. Neither is FDA approved. They are both part of what is called an Emergency Use Authorization, meaning that ideally the FDA would have preferred to have more time to assess their safety, but in view of the need, decided to allow their use as soon as possible.
Are these antiviral medications safe for people with SpA?
Yes, these medications are safe for people with SpA. However, some of the antiviral pills have interactions with other medications; this should be discussed with a provider or pharmacist before starting the medication.
Even though these medications have been approved for use, some in our community are having trouble accessing them – either because pharmacies don’t have them in stock, doctors are requiring an in-person office visit to prescribe them (which may expose others to COVID), or because some doctor’s offices are not yet aware that they can prescribe them. What is your advice?
These drugs are in limited supply, a situation that should begin to improve soon. Even in our own community, availability has changed over time. The monoclonal antibody, sotrovimab, is an alternative to these pills but requires an injection.[Editor’s Note: You can check out SAA’s advocacy campaign for additional tips on what to do if you can’t get a necessary prescription.]
As noted above, these recommendations are subject to change. Discussing these decisions with your health care provider is always encouraged. Furthermore, newer vaccines might prove more effective for the recent COVID-19 variants such as Omicron.