Wednesday, 13 Dec 2017

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Should Lupus Patients Receive Influenza and Pneumococcal Vaccines?

Dr. Barry Waters*:  I have a 21 yr. old lupus nephritis patient on mycophenolate, hydroxychloroquine and prednisone 40 mg per day. She says both her current nephrologist and her prior pediatric rheumatologist told her NOT to get pneumococcal and flu vaccines. I thought she is supposed to get them - any comment?

Dr. Kathryn Dao: The question regarding vaccinating patients with systemic lupus erythematosus (SLE) against influenza and pneumococcal infection is actually a common one. The concerns are whether vaccinations would flare the disease by stimulating an already dysregulated immune system and whether vaccinations are even effective particularly in the setting of aggressive immunosuppressive therapies.

We know that: 1) infection is one of the primary causes of death in patients with SLE; 2) patients with high disease activity or who are on corticosteroids, DMARDS, biologics are at greatest risks for infection; and 3) vaccinations are our greatest tools to prevent infection.

So what is the evidence for or against vaccinating SLE patients?

Influenza vaccination: Currently available influenza vaccines include: the trivalent, quadrivalent, high dose flu, and live-attenuated vaccines. The majority of these vaccines do not contain adjuvants designed to make vaccines more effective (note that only 1 flu vaccine has an adjuvant (Fluad), which recently got a nod from the FDA in September 2015 but currently is not available to the general public as of this publication). Adjuvants, by activating toll-like receptors and the NALP3 inflammasome, have been linked to Autoimmune (or Autoinflammatory) Syndrome Induced by Adjuvants (ASIA) characterized by fever, arthritis, myositis, rash, and in some cases, pericarditis and sclerodactyly in the presence of abnormal autoimmune serologies.

Hence, most studies looked at nonadjuvant vaccines in SLE patients. Many studies were conducted in patients with low disease activity and found that these vaccines are safe and effective in patients with SLE.

The question would be, what happens if you use a nonadjuvant vaccine in a patient with high disease activity? A few published case reports noted precipitation of SLE disease after vaccination; in addition, other studies found an increase in autoantibody levels after vaccination without clinical disease flares. However, these reports included only small numbers of patients (20-50 patients).

In a 2013 study by Campos et al., 118 juvenile SLE patients and 102 matched controls were vaccinated with nonadjuvant influenza A H1N1 vaccine; patients with higher SLEDAI-2K score >8, had higher rates of non-serocoversion (48.8% vs. 24%, p=0.008) compared to controls, but there were no worsening of SLE disease activity (1). Overall, patients with SLE had rate of seroconversion 63.6% compared to controls 91.2%; P < 0.001, comparable to other studies.

  • Bottom line is, while the rates of seroconversion and seroprotection are lower than healthy controls, vaccinating with nonadjuvant flu vaccines is safe in patients with SLE and should be undertaken regardless of disease activity and degree of immunosuppression
    • (avoid live vaccines in those who have contraindications, e.g. : patients with prednisone > 20 mg/day, on biologics).

Pneumococcal vaccination: The most common pneumococcal vaccines our patients need are the pneumococcal conjugate vaccine (PCV13 or Prevnar 13) and the pneumococcal polysaccharide vaccine (PPSV23 or Pneumovax). There are very few studies looking at pneumococcal vaccination in patients with SLE (2-4). These studies, again, included small numbers of patients. Overall, there were no disease flares in patients who were vaccinated. Side effects were mild. One study noted that antibody responses to pneumococcal vaccines were unaffected by prednisone, cyclophosphamide, and azathioprine. During the BLISS-76 trial, the response to pneumoccocal vaccination was evaluated. Patients receiving belimumab did not have a reduced antibody response, consistent with preservation of the memory B cell compartment with this drug.

  • Bottom line: Patients with SLE should be vaccinated with the pneumococcal vaccine.

* Case submitted by Barry Waters, MD, from American Arthritis and Rheumatology Associates; He is also the Rheumatology Program Director at Larkin Community Hospital in Coral Springs, FL

References:
1. Campos LM1 et. al. Arthritis Care Res (Hoboken). 2013 Jul;65(7):1121-7. doi: 10.1002/acr.21948.
2. Tarján P et al. Scand J Rheumatol. 2002;31(4):211-5.
3. Lipnick RN et al. J Rheumatol. 1985 Dec;12(6):1118-21.
4. BLISS-76 Study Group. J Rheumatol. 2012 Aug;39(8):1632-40. Epub 2012 Jun 15.

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Kathryn Dao, MD, FACP, FACR, is the Associate Director of Clinical Rheumatology at Baylor Research Institute in Dallas. She is in clinical practice at the Arthritis Care and Research Center in Dallas, TX and is actively involved in patient care, medical education, and clinical research.  Her interests include Rheumatoid Arthritis, Systemic Lupus Erythematosus, Gout, Infections with Biologics, Osteoporosis, and Drug Safety. She has served as the co-editor for the American College of Rheumatology “Drug Safety Quarterly” 2010-2013.   

 

Rheumatologists' Comments

Conversion rate would be higher if prednisone dose was 20mg/day or less. (J.Decker. Personal Communication during Swine Flu Epidemic)
You are absolutely right. Studies have found prednisone > 20 mg/day, use of immunosuppressive therapies, and high lupus disease activity can lower the seroconversion rate to influenza vaccination. Interestingly, in a 2012 study by Borba et al, 555 SLE patients and 170 healthy controls were eval for response to the influenza vaccine. Patients who were on anti-malarial therapy despite concomitant immunosuppression (including prednisone> 20 mg/day), had similar seroconversion rates to patients who were not on immunosuppressants at all (71.4% vs 72%, p=1.00). The authors noted that anti-malarials may restore immunogenicity to vaccinations (1). This idea had been described before in other studies noting improvement in vaccine response for meningococcal and Tetanus-diphtheria vaccines in patients receiving chloroquine. (Ref:1. Rheumatology (Oxford). 2012 Jun;51(6):1061-9.2. J Infect Dis. (1998) 177 (6): 1762-1765.3. Trans R Soc Trop Med Hyg 1983;77:24-31.)
Kathryn: Good recommendations. In fact, I recommend that all SLE pts get both pneumococcal vaccines (Prevnar and Pneumovax) even if they are only on hydroxychloroquine (HCQ) and are less than 50yo. A study from the Netherlands showed a higher rate for severe pneumococcal infections even in patients who were only on HCQ, and the authors recommended that all SLE patients receive pneumococcal vaccines. Reference = Luijten R, et al. Lupus. 2014 JUL;23(14):1512-1516.
what is the evidence that vaccinations are effective in reducing infection rates for influenza and pneumococcal infections in lupus pts. do we know the rates of these infections in vaccinated and unvaccinated pts.
Tracking cases of infections occurring in vaccinated pop. vs. non-vaccinated pop. would be ideal to evaluate vaccine efficacy. We don't have that kind of epidemiologic data for lupus patients. Surrogate markers of vaccine response (e.g: hemagglutination inhibition assay, seroconversion/seroprotection rates) are all we have. Lupus patients seroconvert and exhibit seroprotection rates after flu vaccination, albeit these numbers are lower compared to controls. It is assumed when the seroprotection rate reaches a certain threshold, a degree of protection against that particular microorganism exists; in studies of patients with various comorbidities, the rates for infx, hospitalizations and deaths were reduced when the seroprotection threshold was met. Also remember, vaccines are only effective against the microorganism that it is designed to target (last year's flu vaccine was a bust because of a poor match). Pneumonia vaccine efficacy data in SLE are scant, but many published reports cited pneumonia as a preventable cause of death. Given that vaccinations are one of the few tools we have to prevent infection with proven safety and efficacy, why wouldn't you vaccinate your patient?