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Vaccinations for patients with autoimmune diseases -- specifically patients being treated with biologics -- bring with them a variety of issues, including disease-specific, medication-related, and vaccine-associated factors, researchers suggested.

Patients with diseases such as rheumatoid arthritis and systemic lupus erythematosus are at increased risk for infections because of aberrations in their immune system and long-term treatments with conventional immunosuppressive therapies.

The concern has become even more acute with the widespread adoption of biologic therapies, as these agents can further increase patients' susceptibility to serious infections. And while published recommendations exist for vaccinations in patients on conventional treatments, no guidelines exist for those on biologics.

To address this gap, , of Hospital Prof. Doutor Fernando Fonseca in Amadora, Portugal, and , of University College London, conducted a literature review and systematic analysis to provide clinicians with what evidence is available thus far, and thereby help guide decision-making.

"We should aim to provide personalized vaccination plans depending on pre-vaccination antibody titers, drug treatments, and immunological potential,"

Practical recommendations they formulated include:

• A comprehensive evaluation of vaccination status should be done whenever possible before biologic treatment is begun.
• Vaccines can be given during anti-tumor necrosis factor (TNF) therapy, but preferably before B-cell targeted treatment, and when disease is stable.
• Live vaccines should not be given, because of the possibility of serious complications and adverse reactions.
• The inactivated pneumococcal and influenza vaccines "are strongly recommended."
• Tetanus toxoid vaccination should be given as for healthy individuals.

However, they noted that "many questions remain unanswered, as the necessary large and well-designed studies to confirm safety and the precise incidence of side effects have yet to be performed."

They also reported on specific findings from the literature for the individual types of medications.

For instance, a concern that's been raised for the TNF inhibitors has been uncertainty about the

Most of the studies evaluating this have only considered seroprotection, which "is not identical with clinical protection," the researchers noted.

Patients on TNF inhibitors also may experience more rapid waning of immunity after pneumococcal vaccination, and therefore may need revaccination as early as 1.5 years after the initial vaccine is given.

Inadequate protection after influenza vaccination also has been seen among patients receiving the B-cell depleting agent rituximab (Rituxan), with particularly

Therefore, "it seems reasonable" to either provide the influenza vaccine before rituximab treatment is initiated, or to wait at least 6 months after the infusion is given.

Less is known about the effects of influenza and pneumococcal vaccines among patients given the interleukin-6 receptor antibody tocilizumab (Actemra). In one study of patients with rheumatoid arthritis, , and in general, immunogenicity was lower when tocilizumab was given with methotrexate.

Response to the pneumococcal vaccine doesn't appear to be impaired in patients with rheumatoid arthritis given tocilizumab, except in the setting of background methotrexate use.

Little also is known about influenza vaccine in patients receiving the T-cell co-stimulation modulator abatacept (Orencia). In studies of patients with rheumatoid arthritis, . There also were decreases in gamma globulins and overall humoral responses in abatacept-treated patients.

Only one study looked at immune responses for influenza, pneumococcus, and tetanus in patients given the B-lymphocyte stimulator inhibitor belimumab (Benlysta), and it found . However, this study was limited by small numbers of patients and inconsistencies in vaccine timing.

Ferreira and Isenberg also reported that no data were available for patients on biologics for other vaccines, including those targeting human papillomavirus, varicella zoster, hepatitis A and B, or Hemophilus influenzae type B.

For varicella, they noted that severe immunodeficiency is a contraindication to receipt of the vaccine, so they don't recommend the live vaccine. Data on the "new and promising" inactivated vaccine aren't yet available, however.

"Some patients on biologics may not be adequately protected because of lower vaccine immunogenicity, and optimization of vaccine delivery to this specific group of patients, including the use of adjuvants and of booster doses, is urgently needed," they concluded.

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