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Curtis, Jeffrey R.; Anthony, Donald D.; Arasaratnam, Reuben J.; Baden, Lindsey R.; Bass, Anne R.; Calabrese, Cassandra; Gravallese, Ellen M.; Harpaz, Rafael; Kroger, Andrew T.; Sadun, Rebecca E.; Turner, Amy S.; Williams, Eleanor Anderson; Mikuls, Ted R.

doi:10.1002/art.41805

Cited by 6 publications

(8 citation statements)

References 6 publications

(6 reference statements)

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“…The critical question is, "what would be the appropriate timing to vaccinate IMDD patients after rituximab treatment?" Experts suggest waiting at least five months after the last rituximab administration (21,22). Our study, corresponding to others, found that vaccinating at less than six months post-rituximab is extremely low yielded since the humoral immune response to COVID-19 vaccines was virtually blocked by rituximab during this period (42)(43)(44)(45).…”

Section: Discussionsupporting

confidence: 69%

“…Our previous study showed that rituximab use was associated with non-seroconversion following COVID-19 vaccination among autoimmune bullous disease patients (20). Avoiding vaccination while rituximab is taking effect, whereby completing vaccination 2-4 weeks before rituximab treatment, is suggested by international practice guidelines (21,22). However, this recommendation may not be practicable for some IMDD patients, such as patients with severe pemphigus, as their disease circumstance may benefit from urgent rituximab treatment (23,24).…”

Section: Introductionmentioning

confidence: 99%

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Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients

Seree-aphinan

Ratanapokasatit²,

Suchonwanit³

et al. 2023

Front. Immunol.

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BackgroundBy depleting circulating B lymphocytes, rituximab time-dependently suppresses coronavirus disease 2019 (COVID-19) vaccines’ humoral immunogenicity for a prolonged period. The optimal time to vaccinate rituximab-exposed immune-mediated dermatologic disease (IMDD) patients is currently unclear.ObjectiveTo estimate the vaccination timeframe that equalized the occurrence of humoral immunogenicity outcomes between rituximab-exposed and rituximab-naïve IMDD patients.MethodsThis retrospective cohort study recruited rituximab-exposed and age-matched rituximab-naïve subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity post-vaccination. Baseline clinical and immunological data (i.e., immunoglobulin levels, lymphocyte immunophenotyping) and SARS-CoV-2-specific immunity levels were extracted. The outcomes compared were the percentages of subjects who produced neutralizing antibodies (seroconversion rates, SR) and SARS-CoV-2-specific IgG levels among seroconverters. The outcomes were first analyzed using multiple regressions adjusted for the effects of corticosteroid use, steroid-spearing agents, and pre-vaccination immunological status (i.e., IgM levels, the percentages of the total, naïve, and memory B lymphocytes) to identify rituximab-related immunogenicity outcomes. The rituximab-related outcome differences with a 95% confidence interval (CI) between groups were calculated, starting by including every subject and then narrowing down to those with longer rituximab-to-vaccination intervals (≥3, ≥6, ≥9, ≥12 months). The desirable cut-off performances were <25% outcome inferiority observed among rituximab-exposed subgroups compared to rituximab-naïve subjects, and the positive likelihood ratio (LR+) for the corresponding outcomes ≥2.FindingsForty-five rituximab-exposed and 90 rituximab-naive subjects were included. The regression analysis demonstrated a negative association between rituximab exposure status and SR but not with SARS-CoV-2-specific IgG levels. Nine-month rituximab-to-vaccination cut-off fulfilled our prespecified diagnostic performance (SR difference between rituximab-exposed and rituximab-naïve group [95%CI]: -2.6 [-23.3, 18.1], LR+: 2.6) and coincided with the repopulation of naïve B lymphocytes in these patients.ConclusionsNine months of rituximab-to-vaccination interval maximize the immunological benefits of COVID-19 vaccines while avoiding unnecessary delay in vaccination and rituximab treatment for IMDD patients.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients

Seree-aphinan

Ratanapokasatit²,

Suchonwanit³

et al. 2023

Front. Immunol.

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“…The main message of these data on vaccination against pneumococci is consistent with our findings on JAK inhibitors regarding monotherapy and on the additive attenuation of the humoral immune response by the additional use of methotrexate. At this point, the American College of Rheumatology explicitly points out the difficulty of extrapolating data from vaccination studies, for example, against influenza, pneumococci, or tetanus, to the current recommendations for immunisation against SARS-CoV-2 [34].…”

Section: Discussionmentioning

confidence: 99%

Janus kinase (JAK) inhibitors significantly reduce the humoral vaccination response against SARS-CoV-2 in patients with rheumatoid arthritis

et al. 2022

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Objectives Recently, a number of studies have explored the possible attenuation of the immune response by disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Our study objective was to investigate the presumed attenuated humoral response to vaccination against SARS-CoV-2 in patients with RA treated with Janus kinase (JAK) inhibitors with or without methotrexate (MTX). The immune responses were compared with controls without RA. Method The humoral vaccination response was evaluated by determining titres of neutralising antibodies against the S1 antigen of SARS-CoV-2. One hundred and thirteen fully vaccinated individuals were included at 6 ± 1 weeks after second vaccination (BioNTech/Pfizer (69.9%), AstraZeneca (21.2%), and Moderna (8.9%)). In a cross-sectional and single-centre study design, we compared titres of neutralising antibodies between patients with ( n = 51) and without ( n = 62) medication with JAK inhibitors. Results Treatment with JAK inhibitors led to a significantly reduced humoral response to vaccination ( P = 0.004). A maximum immune response was seen in 77.4% of control patients, whereas this percentage was reduced to 54.9% in study participants on medication with JAK inhibitors (effect size d = 0.270). Further subanalyses revealed that patients on combination treatment (JAK inhibitors and MTX, 9 of 51 subjects) demonstrated an even significantly impaired immune response as compared to patients on monotherapy with JAK inhibitors ( P = 0.028; d = 0.267). Conclusions JAK inhibitors significantly reduce the humoral response following dual vaccination against SARS-CoV-2. The combination with MTX causes an additional, significant reduction in neutralising IgG titres. Our data suggest cessation of JAK inhibitors in patients with RA in the context of vaccination against SARS-CoV-2. Key Points • It was shown that DMARD therapy with JAK inhibitors in patients with rheumatoid arthritis leads to an attenuation of the humoral vaccination response against SARS-CoV-2. • The effect under medication with JAK inhibitors was significant compared to the control group and overall moderate. • The combination of JAK inhibitors with MTX led to an additive and significant attenuation of the humoral response.

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“…Current guidelines [ 8 ] recommend vaccinating patients with autoimmune and inflammatory rheumatic diseases (AIIRD) whether or not they are using immuno-modulatory agents based on their risk for COVID-19 and these patients are now prioritized for vaccination in many countries [ 9 – 11 ]. Since registration trials of vaccines against SARS-CoV-2 did not include patients with AIIRD [ 12 , 13 ] and current evidence from pre COVID-19 era literature is scarce, there are many unknown questions at this time.…”

Section: Introductionmentioning

confidence: 99%

Antibody response to inactivated COVID-19 vaccine (CoronaVac) in immune-mediated diseases: a controlled study among hospital workers and elderly

et al. 2021

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Objective To assess antibody response to inactivated COVID-19 vaccine in patients with immune-mediated diseases (IMD) among hospital workers and people aged 65 and older. Methods In this cross-sectional study, we studied 82 hospital workers with IMD (mean age: 42.2 ± 10.0 years) and 300 (mean age: 41.7 ± 9.9 years) controls. Among + 65 aged population, we studied 22 (mean age: 71.4 ± 4.5 years) patients and 47 controls (mean age: 70.9 ± 4.8 years). All study subjects had a negative history for COVID-19. Sera were obtained after at least 21 days following the second vaccination. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. Results Patients with IMD were significantly less likely to have detectable antibodies than healthy controls both among the hospital workers (92.7% vs 99.7%, p < 0.001) and elderly population (77.3% vs 97.9%, p = 0.011). Among patients with IMD, those using immunosuppressive or immune-modulating drugs (64/75, 85.3%) were significantly less likely to have detectable antibodies compared to those off treatment (29/29, 100%) ( p = 0.029). Additionally, a negative association between age and the antibody titer categories among patients ( r = − 0.352; p < 0.001) and controls ( r = − 0.258; p < 0.001) were demonstrated. Conclusions Among hospital workers, the vast majority of patients with IMD and immunocompetent controls developed a significant humoral response following the administration of the second dose of inactivated COVID-19 vaccine. This was also true for the elderly population, albeit with lower antibody titers. Immunosuppressive use, particularly rituximab significantly reduced antibody titers. Antibody titers were significantly lower among those aged ≥ 60 years both in patient and control populations. Whether these individuals should get a booster dose warrants further studies. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04910-7.

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Cited by 6 publications

References 6 publications

Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients

Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients

Janus kinase (JAK) inhibitors significantly reduce the humoral vaccination response against SARS-CoV-2 in patients with rheumatoid arthritis

Antibody response to inactivated COVID-19 vaccine (CoronaVac) in immune-mediated diseases: a controlled study among hospital workers and elderly

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