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Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgments
  9. REFERENCES
  10. Appendix: A: THE PGRx LUPUS STUDY GROUP

Objective

Studies have suggested that systemic lupus erythematosus (SLE) may be triggered by vaccinations. We undertook this study to investigate the relationship between vaccination and onset of SLE.

Methods

This international case–control study was conducted between April 2008 and June 2012 in 36 specialist referral centers (34 in France and 2 in Quebec, Canada) and recruited patients ≤60 years old recently diagnosed as having either definite SLE (meeting ≥4 American College of Rheumatology [ACR] criteria including at least 1 immunologic criterion) or probable SLE (meeting 3 ACR criteria including at least 1 immunologic criterion). Controls were recruited from general practice settings through a closely monitored protocol and matched to patients by age, sex, region of residence, and date of recruitment. Vaccinations and other potential risk factors for SLE were assessed using a standardized telephone interview. We compared proportions of patients and controls who were vaccinated 12 and 24 months before the index date (date of first clinical symptom presented by the patient) using odds ratios (ORs) from conditional logistic regression.

Results

We assessed 105 patients (89 with definite SLE and 16 with probable SLE) and 712 controls. Twenty-two of the 105 patients (21.0%) and 181 of the 712 controls (25.4%) had received at least 1 vaccination within 24 months before the index date (adjusted OR 0.9 [95% confidence interval 0.5–1.5]). The proportions of patients and controls vaccinated within the previous 12 months were also similar.

Conclusion

Our study showed no association between exposure to vaccination and risk of developing SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in tissue damage, characterized by involvement of the skin, joints, serum, central nervous system, and kidneys. It occurs as relapses alternating with remissions and is associated with significant morbidity and mortality ([1-4]).

Autoimmunity occurs when the immune system reacts against self antigens, and in most cases, the trigger for this process is largely unknown. Because vaccinations are designed to stimulate an antigen-specific immune response, they have been proposed as potential triggers for autoimmunity and the onset or exacerbation of SLE ([5, 6]). Epidemiologic studies have focused on the relationship between SLE and vaccination with hepatitis B, influenza, and human papillomavirus vaccines ([7-9]), with results from methodologically sound studies conflicting with those from limited case series ([10-13]).

Current public health policies recommend surveillance for adverse events following immunization, particularly for newly licensed vaccines. The Pharmacoepidemiologic General Research eXtension (PGRx) system was designed with this objective in mind. Using this system, we identified 105 patients with recent onset of SLE diagnosed in France and Quebec, Canada over 4 years. Using a case–control study, we explored the overall relationship between vaccination and the onset of SLE.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgments
  9. REFERENCES
  10. Appendix: A: THE PGRx LUPUS STUDY GROUP

Study population

Eligible participants were patients and controls ≤60 years old, residing in France or Quebec, Canada, who could read and respond to a telephone interview (parents could be interviewed for patients <18 years old) and who had no history of SLE (no prior episodes for patients). All participants or their parents signed an informed consent form. This study was based on methods used in a previous study of immune thrombocytopenia ([14]).

Patients

Patients with incident cases of SLE were recruited by 36 internal medicine and rheumatology centers at university and general hospitals across France and Quebec that had agreed to participate in the PGRx SLE registry. These centers were contacted at least every 2 months by external PGRx research assistants to ensure that all eligible patients were approached for recruitment and to monitor data quality and completeness. A list of the members of the PGRx Lupus study group is provided in Appendix A.

Participation in the study was offered to all consecutive patients presenting to these centers between April 1, 2008 and June 11, 2012 with first-ever clinical symptoms suggestive of SLE (not including Raynaud's phenomenon) appearing within 12 months before the recruitment consultation. At each patient's recruitment, the recruiting specialist completed a web-based medical data form that included the clinical features of the case. Patients were followed up for 1 year after recruitment to establish the final diagnostic classification, which was used in this analysis. Cases were classified into 3 categories devised by board-certified specialists: definite SLE (meeting ≥4 American College of Rheumatology [ACR] criteria [15] including at least 1 immunologic criterion [anti-Sm or anti-DNA or antinuclear antibodies]), probable SLE (meeting 3 ACR criteria including at least 1 immunologic criterion), or rejected.

Controls

A total of 420 general practitioners from the same regions as the internal medicine centers participated in this study. They were randomly selected by region from a national list of general practitioners in France and in Quebec. The general practitioners were instructed to recruit the first male and female subjects within the age strata of 18–34, 35–49, 50–64, and 65–79 years presenting to their practice at a starting date previously agreed upon individually with each general practitioner. Control subjects were recruited regardless of the reason for the consultation and independently of any morbidity or exposure criteria.

A registry of 8,469 subjects called referents was constituted. Among these, the research team independently identified all subjects with no history of lupus to constitute the registry of referents eligible to be matched to the cases. For this study, control subjects were randomly selected from the PGRx–general practitioner (GP) registry of eligible referents and matched to patients by age (within ±6 months for patients <18 years old and within ±24 months for patients ≥18 years old), sex, region of residence (northern France, southern France, or Quebec), and recruitment consultation date (within ±2 months and within the same period of the year). Matching by period (February 16 to September 14 or September 15 to February 15) ensured that patients and controls had a similar opportunity to be vaccinated against influenza. As many controls as possible were matched to each patient using an iterative matching process, with controls being dropped from the pool after matching. Physicians were requested to complete an electronic medical data form that included medical information on the control subject (chronic diseases and comorbidities, medical risk factors, biologic data), current prescriptions, and prescriptions for the previous 2 years.

Assessment of vaccination and other potential risk factors for SLE

Patients and controls underwent a standardized telephone interview including questions concerning smoking, alcohol consumption, recent pregnancies, family history of autoimmune disorders, and all medications and vaccines received within the 24 months before the recruitment consultation date. Interviews lasted ∼1 hour and were conducted within 45 days of recruitment by trained interviewers who were blinded to case/referent status. A guide which covered 85 health conditions and associated drugs was provided to patients and controls before the interview. The guide also listed 27 vaccinations, along with available photographs of marketed vaccines. Patients and controls were asked to report any medications and vaccines received, including any not listed ([16, 17]). Vaccinations were included in the analysis if they were reported by the patient or control.

Time windows defining exposure to vaccines for SLE

The index date was the date of the first clinical sign or symptom suggestive of SLE in the patient, as reported by the recruiting specialist. This date also served as the index date for each control matched with the patient. Only factors reported for the period before the index date were included in this analysis. Two time windows were considered for vaccination exposures, 12 months and 24 months before the index date, based on the hypothesis that SLE would take up to 12 or 24 months to develop if vaccination was a trigger.

Study oversight

The study protocol was approved by the Ethical Review Committee of Paris-Ile de France III (Comité de Protection des Personnes Ile de France III) and the French Data Protection Authority (Commission Nationale de l'Informatique et des Libertés). It was also approved by the research ethics committees of the provincial health ministry in Quebec (Comité Central d'Éthique de la Recherche du Ministre de la Santé et des Services Sociaux du Québec) and of the Jewish General Hospital, McGill University Health Centre, Centre Hospitalier Universitaire St. Justine, and Centre Hospitalier de l'Université de Montréal. All participants gave their informed consent to participate.

Statistical analysis

Potential confounders of the relationship between vaccination and SLE included smoking, alcohol consumption, pregnancy in the 24 months before the index date, family history of autoimmune disorders, number of medications taken in the 12 months before the index date, and medications potentially associated with the induction of SLE (chlorpromazine, hydralazine, isoniazid, methyldopa, minocycline, procainamide, and quinidine) in the 24 months before the index date ([18]). With regard to these potential confounders, patients with definite or probable SLE were compared with their matched controls using crude odds ratios (ORs).

In the principal analysis, patients with definite or probable SLE were compared with controls with regard to any vaccination in the 24 and 12 months before the index date by computing adjusted ORs controlled for the potential confounders listed above. A sensitivity analysis repeated the above for patients with definite SLE only.

We also explored the associations between SLE and influenza or DTPP (diphtheria, tetanus, pertussis, poliomyelitis) vaccinations, which were the most common in the study population. The separate adjusted analyses of influenza and DTPP vaccines were also controlled for other vaccines in the 24 months before the index date. Hepatitis B vaccine and other vaccines were reported by too few patients to be analyzed separately.

ORs with 95% confidence intervals (95% CIs) were calculated using conditional logistic regression. The goodness of fit of the multivariate model was tested using Akaike information criterion statistics. The minimum detectable OR for the analysis of any vaccine in the 24 months before the index date was 1.96, assuming 105 cases, 25% exposure to vaccines in matched controls, 4 controls per case, 80% power, and an alpha level of 0.05. Analyses were performed with SAS software version 9.2.

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgments
  9. REFERENCES
  10. Appendix: A: THE PGRx LUPUS STUDY GROUP

A total of 36 specialist centers (34 in France and 2 in Canada) agreed to participate in the PGRx SLE registry and reported cases considered in this study. Overall, 420 general practitioners (394 in France and 26 in Canada) agreed to participate in the PGRx-GP registry and recruited controls considered in this study. A total of 105 patients with incident cases of SLE were included in the study and were matched with 712 controls. The flow chart in Figure 1 shows the recruitment of patients and controls.

image

Figure 1. Flow chart showing the recruitment of cases and controls. SLE = systemic lupus erythematosus.

Download figure to PowerPoint

The baseline demographic and clinical features of the patients are shown in Table 1. The mean ± SD age of the patients at recruitment was 32.9 ± 12.6 years, and the female-to-male ratio was 8.5. Table 1 summarizes the demographic and clinical features at the time of recruitment and does not reflect further information collected during the year of followup. After 1 year of followup, there were 89 definite cases and 16 probable cases of SLE.

Table 1. Demographic and clinical features at diagnosis in the 105 patients with definite or probable systemic lupus erythematosus*
  1. Data shown are from the time of diagnosis and do not reflect further information collected during the year of followup. Except where indicated otherwise, values are the number (%) of patients.

Female94 (89.5)
Age at recruitment, mean ± SD years32.9 ± 12.6
Time elapsed between first signs or symptoms and recruitment, mean ± SD days (range)176.4 ± 111.4 (0–358)
Clinical signs 
Mucosal or cutaneous 
Malar rash16 (15.2)
Photosensitivity27 (25.7)
Mucosal ulcers9 (8.6)
Discoid lupus8 (7.6)
Musculoskeletal 
Nonerosive arthritis involving ≥2 peripheral joints68 (64.8)
Cardiovascular or respiratory 
Pericarditis9 (8.6)
Pleuritis10 (9.5)
Renal 
Proteinuria over 24 hours (>0.5 gm)24 (22.9)
Neurologic or psychiatric 
Epilepsy2 (1.9)
Psychosis0 (0.0)
Hematologic 
Thrombocytopenia (<100,000 platelets/mm3)14 (13.3)
Leukopenia (<4,000 leukocytes/mm3)22 (21.0)
Lymphopenia (<1,500 lymphocytes/mm3)47 (44.8)
Hemolytic anemia4 (3.8)
Immunologic (no. assessed) 
Antinuclear antibodies (102)99 (97.1)
Antibodies to native DNA (103)68 (66.0)
Anti-Sm antibodies21 (20.0)
Antiphospholipid antibodies (91)40 (44.0)
IgG or IgM anticardiolipin antibodies34 (32.4)
Lupus anticoagulant (antiprothrombinase)14 (13.3)
Hypocomplementemia (95)34 (35.8)

Table 2 shows that patients and controls were similar in terms of the matching factors: age (mean ± SD 32.9 ± 12.6 years in the patients and 34.8 ± 13.8 years in the controls), sex (94 female patients [89.5%] and 625 female controls [87.8%]), region of residence, and date of recruitment. Patients and controls were also similar in terms of smoking, alcohol consumption, pregnancy in the 24 months before the index date, family history of autoimmune disorders, and number of medications taken in the 12 months before the index date. Patients were more likely than controls to have received a drug potentially associated with the induction of SLE in the 24 months before the index date (crude OR 8.8 [95% CI 1.8–43.1]).

Table 2. Description of the patients with definite or probable SLE and the controls*
 Patients with definite or probable SLE (n = 105)Controls (n = 712)Crude OR (95% CI)
  1. Except where indicated otherwise, values are the number (%) of patients. SLE = systemic lupus erythematosus; OR = odds ratio; 95% CI = 95% confidence interval; NA = not applicable; DTPP = diphtheria, tetanus, pertussis, poliomyelitis.

  2. a

    Patients were matched to controls recruited during the same period of the same years (e.g., September 15, 2009–February 15, 2010 with September 15, 2009–February 15, 2010).

  3. b

    There were 94 female patients and 625 female controls.

  4. c

    Included the following in first-degree relatives: multiple sclerosis, lupus, rheumatoid arthritis, Crohn's disease, ulcerative colitis, and autoimmune thyroiditis. Only available for patients interviewed after November 9, 2008.

  5. d

    Chlorpromazine, hydralazine, isoniazid, methyldopa, minocycline, procainamide, and quinidine.

Matching factors   
Age, years  NA
Mean ± SD32.9 ± 12.634.8 ± 13.8 
13–1910 (9.5)88 (12.4) 
20–3965 (61.9)376 (52.8) 
40–6030 (28.6)248 (34.8) 
Female94 (89.5)625 (87.8)NA
Period of recruitment consultationa  NA
September 15–February 1542 (40.0)263 (36.9) 
February 16–September 1463 (60.0)449 (63.1) 
Region of residence  NA
Northern France92 (87.6)653 (91.7) 
Southern France10 (9.5)52 (7.3) 
Quebec, Canada3 (2.9)7 (1.0) 
Potential confounding factors   
Smoking   
Current smoker32 (30.5)223 (31.3)0.9 (0.5–1.4)
Former smoker (>1 year ago)17 (16.2)107 (15.0)1.1 (0.6–2.1)
Never smoked56 (53.3)382 (53.7)1 (referent)
Alcohol consumption   
Daily or almost daily3 (2.9)44 (6.2)0.4 (0.1–1.3)
A few times per week8 (7.6)88 (12.4)0.6 (0.3–1.3)
Occasionally or never94 (89.5)580 (81.5)1 (referent)
Pregnant in the 24 months before the index dateb12 (12.8)73 (11.7)0.9 (0.5–1.9)
Family history of autoimmune disordersc   
Yes9 (8.6)56 (7.9)1.0 (0.5–2.1)
No70 (66.7)427 (60.0)1 (referent)
Missing26 (24.8)229 (32.2)
Number of medications taken in the 12 months before the index date   
0–514 (13.3)126 (17.7)1 (referent)
>591 (86.7)586 (82.3)1.5 (0.8–2.8)
Medication potentially associated with the induction of SLE in the 24 months before the index dated   
Yes4 (3.8)3 (0.4)8.8 (1.8–43.1)
No101 (96.2)709 (99.6)1 (referent)
Vaccine exposure   
Any vaccine in the 24 months before the index date22 (21.0)181 (25.4)0.8 (0.5–1.4)
DTPP only8 (7.6)65 (9.1)1.0 (0.4–2.3)
Influenza only10 (9.5)78 (11.0)0.9 (0.4–1.8)
DTPP or influenza17 (16.2)137 (19.2)0.9 (0.5–1.6)
Hepatitis B3 (2.9)18 (2.5)1.2 (0.3–4.5)
Other vaccines3 (2.9)31 (4.4)0.6 (0.2–2.0)

Proportions of patients (those with definite or probable SLE) and controls who received any vaccination within 24 months before the index date were 21.0% (n = 22) and 25.4% (n = 181), respectively (adjusted OR 0.9 [95% CI 0.5–1.5]), and proportions of patients and controls who received any vaccination within 12 months before the index date were 16.2% (n = 17) and 20.8% (n = 148), respectively (adjusted OR 0.9 [95% CI 0.5–1.6]) (Table 3). Proportions of patients and controls who received a vaccination against influenza within 24 months before the index date were 7.6% (n = 8) and 9.1% (n = 65), respectively (adjusted OR 1.1 [95% CI 0.5–2.6]), and proportions of patients and controls who received a DTPP vaccination within 24 months before the index date were 9.5% (n = 10) and 11.0% (n = 78), respectively (adjusted OR 0.9 [95% CI 0.4–1.9]) (Table 3). Hepatitis B vaccines were not analyzed separately because only 3 patients (2.9%) and 18 controls (2.5%) received this vaccine in the 24 months before the index date.

Table 3. Comparison of exposure to vaccination in patients with definite or probable SLE and in controls*
 Patients with definite or probable SLE (n = 105)Controls (n = 712)Crude OR (95% CI)Adjusted OR (95% CI)a
  1. Values are the number (%) of patients. See Table 2 for definitions.

  2. a

    Adjusted for smoking, alcohol consumption, pregnancy in the 24 months before the index date, family history of autoimmune disorders, number of medications taken in the 12 months before the index date, and medication potentially associated with the induction of SLE in the 24 months before the index date.

  3. b

    OR also adjusted for vaccination with any vaccine other than influenza in the 24 months before the index date.

  4. c

    OR also adjusted for vaccination with any vaccine other than DTPP in the 24 months before the index date.

Exposure to any vaccine(s)    
24 months before the index date    
Exposure in this time window22 (21.0)181 (25.4)0.8 (0.5–1.4)0.9 (0.5–1.5)
Missing date of vaccination0 (0.0)14 (2.0)
No exposure in this time window83 (79.0)517 (72.6)1 (referent)1 (referent)
12 months before the index date    
Exposure in this time window17 (16.2)148 (20.8)0.8 (0.5–1.4)0.9 (0.5–1.6)
Missing date of vaccination0 (0.0)15 (2.1)
No exposure in this time window88 (83.8)549 (77.1)1 (referent)1 (referent)
Exposure to influenza vaccine(s)    
24 months before the index dateb    
Exposure in this time window8 (7.6)65 (9.1)1.0 (0.4–2.3)1.1 (0.5–2.6)
Missing date of vaccination0 (0.0)4 (0.6)
No exposure in this time window97 (92.4)643 (90.3)1 (referent)1 (referent)
12 months before the index dateb    
Exposure in this time window8 (7.6)60 (8.4)1.1 (0.5–2.4)1.2 (0.5–2.9)
Missing date of vaccination0 (0.0)4 (0.6)
No exposure in this time window97 (92.4)648 (91.0)1 (referent)1 (referent)
Exposure to DTPP vaccine(s)    
24 months before the index datec    
Exposure in this time window10 (9.5)78 (11.0)0.9 (0.4–1.8)0.9 (0.4–1.9)
Missing date of vaccination0 (0.0)13 (1.8)
No exposure in this time window95 (90.5)621 (87.2)1 (referent)1 (referent)
12 months before the index datec    
Exposure in this time window5 (4.8)61 (8.6)0.6 (0.2–1.7)0.7 (0.3–1.9)
Missing date of vaccination0 (0.0)13 (1.8)
No exposure in this time window100 (95.2)638 (89.6)1 (referent)1 (referent)

A series of sensitivity analyses was performed to further investigate the association between SLE and vaccination. No significant differences were found between patients with definite SLE (those with probable SLE excluded) and their matched controls in terms of any vaccination in either the 24 months (adjusted OR 0.8 [95% CI 0.5–1.6]) or the 12 months (adjusted OR 0.9 [95% CI 0.5–1.7]) before the index date. An analysis was also performed for age groups. When we compared those ages 13–29 years (53 patients with 320 controls) and those ages ≥30 years (52 patients with 392 controls), the adjusted ORs were 1.1 (95% CI 0.5–2.3) and 0.7 (95% CI 0.3–1.6), respectively. Finally, when we excluded patients exposed to drugs potentially associated with the induction of SLE, the adjusted OR for exposure to any vaccine in the 24 months before the index date was 0.8 (95% CI 0.5–1.3).

DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgments
  9. REFERENCES
  10. Appendix: A: THE PGRx LUPUS STUDY GROUP

We found no evidence that vaccination was associated with an increase in the incidence of SLE. Strengths of the study include the fact that all methods for the collection of cases, controls, and data were standardized and validated to reduce the potential for bias ([16, 17, 19]). Any selection or diagnostic bias was likely to be minimal; patients and controls were recruited for a prospective registry of disorders (PGRx) without any specific hypothesis, so recruiters were unlikely to be biased concerning specific hypotheses. SLE was diagnosed according to strict criteria, and patients with a history of SLE were excluded. This ensured that, as far as possible, relationships between vaccinations and SLE were described for incident cases. Specialist centers recruiting patients and general practices recruiting referents were widespread throughout France and Quebec, so the study population was likely to be broadly generalizable to the French or Quebecois population. Referents in the French PGRx-GP registry were found to be representative of the population in contact with the French health care system in terms of their reasons for consultation (results available on request from the corresponding author) ([20]).

Ascertainment of vaccination was likely to be relatively complete. Indeed, concordance within the PGRx between patients' reports of drug use and physicians' prescriptions has been described and reported elsewhere ([16, 17, 21]). We compared our patients' and controls' self-reported exposure to vaccines with medical reports on 7,613 French patients for whom both sources of information were available. We found that overall agreement was good and varied from substantial (κ = 0.74 for influenza) to high (κ = 0.90 for pneumococcal and human papillomavirus) depending on the vaccine ([16]). Similar agreement was found in a study addressing the relationship between influenza vaccination and Guillain-Barré syndrome ([21]). The matching strategy ensured that patients and controls were relatively comparable.

Our study concerned the risk of first onset of SLE but did not address the risk of SLE flare. Studies among SLE patients have found no increased risk of exacerbation following immunization with pneumococcal ([22-24]), tetanus toxoid ([22]), Haemophilus influenzae type B ([22]), influenza ([24-29]), A H1N1 influenza ([30]), and hepatitis B ([9, 31]) vaccines.

A limitation of this study relating to its small sample size is the possibility that confounders of the relationship between vaccinations and SLE may not have been well controlled for. Indeed, we found no associations between SLE and any of the potential confounding factors studied, including pregnancy, smoking, and alcohol consumption, except for certain medications known to be associated with the induction of SLE. The literature provides conflicting results regarding the effects of smoking, alcohol consumption, and pregnancy on SLE. Some studies have suggested that smoking is associated with an increased risk of SLE ([32, 33]); others have found no clear effect ([34, 35]), and 1 study suggested that the effect may be stronger for cutaneous lupus erythematosus than for SLE ([36]). In contrast, our results are consistent with findings of a decreased risk of SLE with alcohol consumption ([33, 37]). Other studies have shown no significant effect ([36]) or have suggested that the apparent protective effect may be due to SLE patients quitting drinking because of their symptoms ([38]). In women previously diagnosed as having SLE, pregnancy has been associated with flares of the disease ([39]). However, few studies have investigated the onset of SLE in relation to pregnancy, and we found no significant association between the two.

For the most part, autoimmune diseases in family members have not been associated with SLE ([37]), as we found in this study. However, our study was not sufficiently powered to allow for the assessment of SLE risk factors. The number of medications taken in the 12 months before the index date was analyzed as a proxy variable for contact with health services, as increased contact may increase the potential for vaccination. We found that patients and controls were similar in this regard. As expected, various drugs were strongly associated with SLE ([18]), and we controlled for these while investigating the effect of vaccinations on SLE. Finally, given that collecting information on ethnicity is not allowed in France and is limited in Quebec by ethics and regulatory bodies, we were not able to include this potential confounder in the analysis, and this is therefore an additional limitation of our study.

This study was powered to detect a minimum OR of 1.96 given the number of patients recruited and the prevalence of exposure to vaccines within the considered time windows. Although a minimum OR of 1.96 is fairly large, it is nevertheless a valid effort to deter a potential risk. The actual OR at 0.9 (95% CI 0.5–1.5) was in fact less than 1, and the upper limit of the confidence interval was inferior to the minimum detectable OR, which reinforces our confidence in the results suggesting a lack of risk. The separate analyses conducted for influenza and DTPP vaccinations were underpowered but were presented mostly to show the magnitude of the estimate; these were both consistent with the overall OR. Very large databases, such as administrative health care databases, are necessary for detecting low risk or investigating the association between specific vaccines and SLE with sufficient power. However, in general, these databases do not allow the use of strict diagnostic criteria and the precise measurement of risk factors (e.g., family history, life habits, etc.) and potential confounders. A significant effort was made in our study to corroborate cases and exposure status so as to ensure sufficient power calculation to accurately represent the pathology of interest and not to have the study undermined by misclassification of either case–control status or exposure status.

In summary, our study shows that exposure to vaccines is not associated with an increased risk of developing SLE. Although our study has some limitations, we are reassured by the finding that the ORs for the relationship between vaccination and SLE onset are less than 1.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgments
  9. REFERENCES
  10. Appendix: A: THE PGRx LUPUS STUDY GROUP

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Grimaldi-Bensouda had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Grimaldi-Bensouda, Le Guern, Kone-Paut, Aubrun, Fain, Ruel, Machet, Viallard, Magy-Bertrand, Daugas, Rossignol, Abenhaim, Costedoat-Chalumeau.

Acquisition of data. Grimaldi-Bensouda, Le Guern, Kone-Paut, Aubrun, Fain, Ruel, Machet, Viallard, Magy-Bertrand, Daugas, Rossignol, Abenhaim, Costedoat-Chalumeau.

Analysis and interpretation of data. Grimaldi-Bensouda, Le Guern, Kone-Paut, Aubrun, Fain, Ruel, Machet, Viallard, Magy-Bertrand, Daugas, Rossignol, Abenhaim, Costedoat-Chalumeau.

ROLE OF THE STUDY SPONSOR

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgments
  9. REFERENCES
  10. Appendix: A: THE PGRx LUPUS STUDY GROUP

LA-SER funded the study and was responsible for the design, conduct, and reporting of the research. Publication of this article was contigent upon approval by LA-SER.

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgments
  9. REFERENCES
  10. Appendix: A: THE PGRx LUPUS STUDY GROUP
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Appendix: A: THE PGRx LUPUS STUDY GROUP

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. ROLE OF THE STUDY SPONSOR
  8. Acknowledgments
  9. REFERENCES
  10. Appendix: A: THE PGRx LUPUS STUDY GROUP

Members of the PGRx Lupus study group are as follows: Dr. Emma Allain-Launay, Hôpital Mère-Enfant, Nantes, France; Dr. Murray Baron, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada; Dr. Pablo Bartolucci, Hôpital Henri Mondor, Creteil, France; Prof. Olivier Benveniste, CHU La Pitié-Salpêtrière, Paris, France; Dr. Cécile Bossu-Estour, Clinique Mutualiste des Eaux Claires, Grenoble, France; Dr. Anne Bourgarit, Hôpital Saint Louis, Paris, France; Dr. Benoît Brihaye, Hôpital Bichat, Paris, France; Dr. Emmanuel Chatelus, Hôpital Hautepierre, Strasbourg, France; Dr. Gaëlle Chedeville, The Montreal Children's Hospital, Montreal, Quebec, Canada; Prof. Jacqueline Chevrant-Breton, Hôpital Pontchaillou, Rennes, France; Dr. Nathalie Costedoat-Chalumeau, CHU La Pitié-Salpêtrière, Paris, France; Dr. Eric Daugas, CHU Bichat, Paris, France; Prof. Jean-Marc Durand, Hôpital de la Conception, Marseille, France; Prof. Olivier Fain, Hôpital Jean Verdier, Bondy, France; Dr. Justine Gellen-Dautremer, Hôpital Lariboisière, Paris, France; Dr. Constance Guillaud, Hôpital Henri Mondor, Creteil, France; Dr. Sylvie Hesse, CHU La Timone, Marseille, France; Dr. Brigitte Hillion, CH Lagny, Lagny-Sur-Marne, France; Dr. Pascal Hilliquin, CH Sud Francilien, Corbeil Essonne, France; Dr. Irène Jarrin, Hôpital Lariboisière, Paris, France; Dr. Homa Keshmandt, CHU Saint Louis, Paris, France; Dr. Mehdi Khellaf, Hôpital Henri Mondor, Creteil, France; Prof. Isabelle Kone-Paut, CHU Le Kremlin-Bicêtre, Le Kremlin-Bicêtre, France; Dr. Veronique Le Guern, Hôpital Cochin, Paris, France; Dr. Eduoard Letellier, Hôpital Jean Verdier, Bondy, France; Dr. Nicolas Limal, Hôpital Henri Mondor, Creteil, France; Dr. Laurent Machet, Hôpital Trousseau, Chambray-Les-Tours, France; Dr. Nadine Magy-Bertrand, CHU Jean Minjoz, Besançon, France; Dr. Mathieu Mahevas, Hôpital Henri Mondor, Creteil, France; Dr. Anne-Sophie Morin, CHU Jean Verdier, Bondy, France; Dr. Elisa Pasqualoni, Hôpital Bichat, Paris, France; Dr. Dominique Pez, Hôpital Tenon, Paris, France; Dr. Beatrice Pallot Prades, CHU Saint Etienne, Saint Etienne, France; Dr. Pascal Richette, Hôpital Lariboisière, Paris, France; Dr. Michel Ruel, Hôpital Max Fourestier, Nanterre, France; and Dr. Karim Sacre, Hôpital Bichat, Paris, France.