Meningococcal Vaccine Is Safe, Effective in JIA

The meningococcal C conjugate vaccine can be safely and effectively administered to children with juvenile idiopathic arthritis, without aggravating disease activity or increasing relapse frequency, according to study results.

In 2002, Dutch health authorities initiated a national campaign to promote vaccination of all children aged 1–19 years against meningococcal serogroup C disease, but guideline recommendations were nonspecific regarding exclusion of patients with autoimmune diseases and patients on immunosuppressive therapy.

Therefore, Dr. Evelien Zonneveld-Huijssoon, of Wilhelmina Children's Hospital at University Medical Center Utrecht (the Netherlands), and colleagues undertook a study to determine whether vaccination exacerbates disease activity in patients with autoimmune disease and to assess the effect of immunosuppressive medication on vaccine efficacy.

Children with juvenile idiopathic arthritis (JIA) were selected as the study population. Investigators monitored JIA disease activity and immune responses before and after inoculation with a meningococcal C (MenC) conjugate vaccine (Arthritis Rheum. 2007;56:639–46).

A total of 234 JIA patients enrolled in the study. All patients were aged 1–19 years and attended one of the five pediatric rheumatology outpatient clinics participating in the study. The majority of the patients were female (65%), and mean disease duration was 5.9 years.

Patients were followed clinically for 6 months before and after vaccination. The primary outcome measure was disease relapse. Regardless of JIA disease activity, each patient received a single intramuscular dose of the vaccine during the national vaccination campaign and reported the vaccination date on a study questionnaire. Patients provided blood samples for serologic analysis before vaccination and within 12 weeks after vaccination.

Disease activity was measured using six core set criteria for juvenile arthritis disease activity: physician global assessment, the well-being and disability scales of the Childhood Health Assessment Questionnaire, active joints, limited range of motion, and erythrocyte sedimentation rate. Relapse was considered most likely to occur in the month immediately after vaccination, which was defined as the period of vaccine exposure.

For data analysis, the remaining 11 months of the study period were considered the unexposed period.

Patients for which postvaccination blood samples were available were classified into four groups based on medication use. Patients in group 1 used no medication (47); group 2 used NSAID monotherapy (41); and group 3 used low-dose methotrexate (36) or sulfasalazine (7), with or without NSAIDs. Group 4 consisted of patients receiving high-dose methotrexate (15), methotrexate and sulfasalazine combination therapy (2), infliximab (2), etanercept (6), or cyclosporin A (1), with or without NSAIDs.

Disease activity did not worsen following vaccination, and vaccination did not increase the frequency of disease relapse. Over the 12-month study period, 158 relapses occurred in 97 patients, with 10 patients experiencing disease relapse in the month following vaccination. Risk of relapse in the month following vaccination (exposed period) was 6%, compared with an 8% risk of relapse in the remaining 11 months. Comparable results were seen when the exposed period was defined as 2, 3, or 6 months following vaccination.

Serologic analysis was performed on 141 prevaccination samples and 157 postvaccination samples, including 133 paired samples. Anti-MenC total IgG antibodies in serum were measured by an enzyme-linked immunosorbent assay with a lower limit of detection of 0.24 mcg/mL.

Anti-tetanus toxin antibodies were measured using a tetanus toxin-binding inhibition assay with a lower limit of detection of 0.01 IU/mL. Patients were classified as low responders if postvaccination anti-MenC IgG levels were not greater than 2 mcg/ml.

In the overall study population, anti-MenC IgG geometric mean concentrations increased significantly from 0.4 mcg/mL to 28.9 mcg/mL following vaccination. As expected, postvaccination concentrations were lower in medication groups 3 and 4 (18 and 16, respectively), compared with groups 1 and 2 (41 and 47, respectively).

Four patients were considered low responders. Further testing using serum bactericidal assays (SBA) against serogroup C strain was performed using sera from the 4 low responders and 10 randomly selected serum samples from high responders. The four low responders had postvaccination bactericidal titers within the range indicating an effective bactericidal response, and there were no significant difference in SBA titers in the low responders, compared with the high responders.

“The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive therapy,” wrote Dr. Zonneveld-Huijssoon and colleagues. Study results showed the MenC conjugate vaccine to be safe and effective for use in children with JIA.

The meningococcal C conjugate vaccine can be safely and effectively administered to children with juvenile idiopathic arthritis, without aggravating disease activity or increasing relapse frequency, according to study results.

In 2002, Dutch health authorities initiated a national campaign to promote vaccination of all children aged 1–19 years against meningococcal serogroup C disease, but guideline recommendations were nonspecific regarding exclusion of patients with autoimmune diseases and patients on immunosuppressive therapy.

Therefore, Dr. Evelien Zonneveld-Huijssoon, of Wilhelmina Children's Hospital at University Medical Center Utrecht (the Netherlands), and colleagues undertook a study to determine whether vaccination exacerbates disease activity in patients with autoimmune disease and to assess the effect of immunosuppressive medication on vaccine efficacy.

Children with juvenile idiopathic arthritis (JIA) were selected as the study population. Investigators monitored JIA disease activity and immune responses before and after inoculation with a meningococcal C (MenC) conjugate vaccine (Arthritis Rheum. 2007;56:639–46).

A total of 234 JIA patients enrolled in the study. All patients were aged 1–19 years and attended one of the five pediatric rheumatology outpatient clinics participating in the study. The majority of the patients were female (65%), and mean disease duration was 5.9 years.

Patients were followed clinically for 6 months before and after vaccination. The primary outcome measure was disease relapse. Regardless of JIA disease activity, each patient received a single intramuscular dose of the vaccine during the national vaccination campaign and reported the vaccination date on a study questionnaire. Patients provided blood samples for serologic analysis before vaccination and within 12 weeks after vaccination.

Disease activity was measured using six core set criteria for juvenile arthritis disease activity: physician global assessment, the well-being and disability scales of the Childhood Health Assessment Questionnaire, active joints, limited range of motion, and erythrocyte sedimentation rate. Relapse was considered most likely to occur in the month immediately after vaccination, which was defined as the period of vaccine exposure.

For data analysis, the remaining 11 months of the study period were considered the unexposed period.

Patients for which postvaccination blood samples were available were classified into four groups based on medication use. Patients in group 1 used no medication (47); group 2 used NSAID monotherapy (41); and group 3 used low-dose methotrexate (36) or sulfasalazine (7), with or without NSAIDs. Group 4 consisted of patients receiving high-dose methotrexate (15), methotrexate and sulfasalazine combination therapy (2), infliximab (2), etanercept (6), or cyclosporin A (1), with or without NSAIDs.

Disease activity did not worsen following vaccination, and vaccination did not increase the frequency of disease relapse. Over the 12-month study period, 158 relapses occurred in 97 patients, with 10 patients experiencing disease relapse in the month following vaccination. Risk of relapse in the month following vaccination (exposed period) was 6%, compared with an 8% risk of relapse in the remaining 11 months. Comparable results were seen when the exposed period was defined as 2, 3, or 6 months following vaccination.

Serologic analysis was performed on 141 prevaccination samples and 157 postvaccination samples, including 133 paired samples. Anti-MenC total IgG antibodies in serum were measured by an enzyme-linked immunosorbent assay with a lower limit of detection of 0.24 mcg/mL.

Anti-tetanus toxin antibodies were measured using a tetanus toxin-binding inhibition assay with a lower limit of detection of 0.01 IU/mL. Patients were classified as low responders if postvaccination anti-MenC IgG levels were not greater than 2 mcg/ml.

In the overall study population, anti-MenC IgG geometric mean concentrations increased significantly from 0.4 mcg/mL to 28.9 mcg/mL following vaccination. As expected, postvaccination concentrations were lower in medication groups 3 and 4 (18 and 16, respectively), compared with groups 1 and 2 (41 and 47, respectively).

Four patients were considered low responders. Further testing using serum bactericidal assays (SBA) against serogroup C strain was performed using sera from the 4 low responders and 10 randomly selected serum samples from high responders. The four low responders had postvaccination bactericidal titers within the range indicating an effective bactericidal response, and there were no significant difference in SBA titers in the low responders, compared with the high responders.

“The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive therapy,” wrote Dr. Zonneveld-Huijssoon and colleagues. Study results showed the MenC conjugate vaccine to be safe and effective for use in children with JIA.

The meningococcal C conjugate vaccine can be safely and effectively administered to children with juvenile idiopathic arthritis, without aggravating disease activity or increasing relapse frequency, according to study results.

In 2002, Dutch health authorities initiated a national campaign to promote vaccination of all children aged 1–19 years against meningococcal serogroup C disease, but guideline recommendations were nonspecific regarding exclusion of patients with autoimmune diseases and patients on immunosuppressive therapy.

Therefore, Dr. Evelien Zonneveld-Huijssoon, of Wilhelmina Children's Hospital at University Medical Center Utrecht (the Netherlands), and colleagues undertook a study to determine whether vaccination exacerbates disease activity in patients with autoimmune disease and to assess the effect of immunosuppressive medication on vaccine efficacy.

Children with juvenile idiopathic arthritis (JIA) were selected as the study population. Investigators monitored JIA disease activity and immune responses before and after inoculation with a meningococcal C (MenC) conjugate vaccine (Arthritis Rheum. 2007;56:639–46).

A total of 234 JIA patients enrolled in the study. All patients were aged 1–19 years and attended one of the five pediatric rheumatology outpatient clinics participating in the study. The majority of the patients were female (65%), and mean disease duration was 5.9 years.

Patients were followed clinically for 6 months before and after vaccination. The primary outcome measure was disease relapse. Regardless of JIA disease activity, each patient received a single intramuscular dose of the vaccine during the national vaccination campaign and reported the vaccination date on a study questionnaire. Patients provided blood samples for serologic analysis before vaccination and within 12 weeks after vaccination.

Disease activity was measured using six core set criteria for juvenile arthritis disease activity: physician global assessment, the well-being and disability scales of the Childhood Health Assessment Questionnaire, active joints, limited range of motion, and erythrocyte sedimentation rate. Relapse was considered most likely to occur in the month immediately after vaccination, which was defined as the period of vaccine exposure.

For data analysis, the remaining 11 months of the study period were considered the unexposed period.

Patients for which postvaccination blood samples were available were classified into four groups based on medication use. Patients in group 1 used no medication (47); group 2 used NSAID monotherapy (41); and group 3 used low-dose methotrexate (36) or sulfasalazine (7), with or without NSAIDs. Group 4 consisted of patients receiving high-dose methotrexate (15), methotrexate and sulfasalazine combination therapy (2), infliximab (2), etanercept (6), or cyclosporin A (1), with or without NSAIDs.

Disease activity did not worsen following vaccination, and vaccination did not increase the frequency of disease relapse. Over the 12-month study period, 158 relapses occurred in 97 patients, with 10 patients experiencing disease relapse in the month following vaccination. Risk of relapse in the month following vaccination (exposed period) was 6%, compared with an 8% risk of relapse in the remaining 11 months. Comparable results were seen when the exposed period was defined as 2, 3, or 6 months following vaccination.

Serologic analysis was performed on 141 prevaccination samples and 157 postvaccination samples, including 133 paired samples. Anti-MenC total IgG antibodies in serum were measured by an enzyme-linked immunosorbent assay with a lower limit of detection of 0.24 mcg/mL.

Anti-tetanus toxin antibodies were measured using a tetanus toxin-binding inhibition assay with a lower limit of detection of 0.01 IU/mL. Patients were classified as low responders if postvaccination anti-MenC IgG levels were not greater than 2 mcg/ml.

In the overall study population, anti-MenC IgG geometric mean concentrations increased significantly from 0.4 mcg/mL to 28.9 mcg/mL following vaccination. As expected, postvaccination concentrations were lower in medication groups 3 and 4 (18 and 16, respectively), compared with groups 1 and 2 (41 and 47, respectively).

Four patients were considered low responders. Further testing using serum bactericidal assays (SBA) against serogroup C strain was performed using sera from the 4 low responders and 10 randomly selected serum samples from high responders. The four low responders had postvaccination bactericidal titers within the range indicating an effective bactericidal response, and there were no significant difference in SBA titers in the low responders, compared with the high responders.

“The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive therapy,” wrote Dr. Zonneveld-Huijssoon and colleagues. Study results showed the MenC conjugate vaccine to be safe and effective for use in children with JIA.