Introduction
Vaccine | Vaccine platform | Mechanism of action | Posology for general population |
---|---|---|---|
BNT162b2 Pfizer/BioNTech | mRNA based | Lipid nanoparticles enter host cells and insert mRNA into the cytoplasm. Translation of S protein stimulates both humoral and cellular immune responses | Primary vaccination course: 2 doses, at least 8 weeks apart Booster/reinforcing/third dose is recommended at least 3 months after the primary course |
mRNA-1273 (Moderna) | mRNA based | Lipid nanoparticles enter host cells and insert mRNA into the cytoplasm. Translation of S protein stimulates both humoral and cellular immune responses | Primary vaccination course: 2 doses, at least 8 weeks apart Booster/reinforcing/third dose is recommended at least 3 months after the primary course |
ChAdOx1-S Oxford/AstraZeneca | Deficient chimpanzee adenovirus | Replication-deficient chimpanzee adenovirus contains DNA encoding S protein. The DNA is released into the cytoplasm, migrates into the cell nucleus and host enzymes transcribe mRNA, which migrates back to the cytoplasm. Here, it interacts with host cell ribosomes to enable S protein translation | Primary vaccination course: 2 doses, at least 8 weeks apart Booster/reinforcing/third dose is recommended at least 3 months after the primary course |
Janssen Ad26.COV2-S | Deficient adenovirus-26 | Replication-incompetent recombinant human adenovirus type 26 vector contains DNA encoding S protein. Host enzymes in the cell nucleus transcribe mRNA, which then migrates to the cytoplasm, where S protein translation takes place | Primary vaccination course: 1 dose Booster/reinforcing/second dose of Janssen COVID-19 vaccine not recommended by US Advisory Committee on Immunization Practices due to reports of thrombosis with thrombocytopenia syndrome (TTS) [9]. Preferential use of mRNA COVID-19 vaccines recommended over the Janssen COVID-19 vaccine for primary and booster vaccination in all individuals aged ≥ 18 years in the USA [9] |
Novavax COVID-19 Vaccine, Adjuvanted | Subunit protein | Recombinant S protein nanoparticle combined with Matrix-M adjuvant | Primary vaccination course: 2 doses, at least 3 weeks apart Booster/reinforcing/third dose not yet approved |
The Impact of Immune-Modifying Therapy on the Immune Response to COVID-19 Vaccines
Methods: Literature Search Strategy
Results: Summary of Findings from Literature Search
Study | Study population (number of individuals, n) | Demographics | Immune-modifying therapy | COVID-19 vaccine | Immune response after first dose of COVID-19 vaccine | Immune response after second dose of COVID-19 vaccine |
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Al-Janabi et al. [18] | IMIDs (n = 120) including psoriasis, PsA, RA, SLE and Crohn’s disease No controls | Median age: 53 years Gender: 49 (41%) female Ethnicity 111 (92.5%) White, 9 (7.5%) Asian | Standard systemic Apremilast, ciclosporin, dimethyl fumarate, methotrexate and prednisone Targeted Abatacept, adalimumab, brodalumab, certolizumab, etanercept, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab | BNT162b2 (60/120, 50%) ChAdOx1 nCoV-19 (60/120, 50%) | Humoral Seroconversion 23/31 (74%) patients on standard immune-modifying therapy had detectable antibodies vs 73/81 (90%) on targeted immune-modifying therapy at 34 days post-vaccine Use of standard immune-modifying therapy reduced the odds of a detectable antibody response vs targeted immune-modifying therapy (adjusted OR 0.31) | N/A |
Ammitzbøll et al. [19] | SLE (n = 61) and RA (n = 73) No controls | Median age: SLE – 60 years RA – 70 years Gender: SLE – 41 (77.1%) female RA – 49 (67.1%) female Ethnicity: Not included | Standard systemic Azathioprine, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, prednisone and salazopurine Targeted Abatacept, belimumab, JAKi, IL-6i, rituximab, TNFi | BNT162b2 | N/A | Humoral Seroconversion 103/134 (77%) patients had detectable antibodies at 8 days post-second vaccine dose. A lower proportion of patients with RA than SLE had detectable antibodies (49/73 [67%] vs 54/61 [89%]) 4/17 (24%) patients receiving rituximab had detectable antibodies vs 0/6 (0%) receiving rituximab/methotrexate co-therapy |
Boekel et al. [20] | IMIDs including RA, PsA, ankylosing spondylitis, axial/peripheral spondyloarthritis, juvenile idiopathic arthritis, SLE, vasculitis, PMR, Sjögren’s disease, multiple sclerosis, sarcoidosis, systemic sclerosis, myositis, mixed connective tissue disease (n = 632) Healthy controls (n = 289) | Mean age: IMIDs – 63 years Healthy controls – 63 years Gender: IMIDs – 423 (67%) female Healthy controls – 195 (67%) female Ethnicity: Not included | Standard systemic Azathioprine, ciclosporin, hydroxychloroquine, leflunomide, methotrexate, prednisone and sulfasalazine Targeted Abatacept, ixekizumab, natalizumab, ocrelizumab, rituximab, secukinumab, tocilizumab, ustekinumab, and TNFi | ChAdOx1 nCoV-19 (514/921, 56%) BNT162b2 (460/921, 50%) mRNA-1273 (55/921 6%) Ad.26.COV2.S (3/921, 0.3%) | Humoral Seroconversion 210/432 (49%) individuals with IMIDs had detectable antibodies vs 154/210 (73%) healthy controls (adjusted OR 0·33; p < 0·0001) at 34 vs 36 days post vaccine, respectively 43/133 (32%) individuals with IMIDs on methotrexate, 1/18 (6%) on rituximab/ocrelizumab, and 24/36 (67%) on TNFi had detectable antibodies | Humoral Seroconversion 97/106 (92%) individuals with IMIDs had detectable antibodies vs 38/40 (95%) healthy controls at 38 and 42 days post second dose, respectively 17/18 (94%) individuals with IMIDs on methotrexate, 3/7 (43%) on rituximab/ocrelizumab, and 14/14 (100%) on TNFi had detectable antibodies |
Bonelli et al. [21] | Rheumatological disease (n = 5) including immune-mediated necrotizing myopathy, ANCA-associated vasculitis, eosinophilic granulomatosis, SLE and mixed connective tissue disease Healthy controls: vaccinated (n = 4) and unvaccinated (n = 4) | Median age: Rheumatological disease – 49 years Gender: Rheumatological disease – 3 (60%) females Ethnicity: Not included Demographics for controls not included | Targeted Rituximab | BNT162b2 | N/A | Humoral Seroconversion 2 of 5 (40%) individuals receiving rituximab had detectable antibodies at 23 days post second vaccination Cellular IFN-γ response was detected in the rituximab-treated group (5/5, 100%) and vaccinated healthy control group (4/4, 100%), independent of the humoral immune response |
Boyarsky et al. [22] | Rheumatological disease (n = 123) including inflammatory arthritis (28%), SLE (20%), Sjogren’s syndrome (13%) and overlap connective tissue diseases (29%) No controls | Mean age: 50 years Gender: 117 (95%) female Ethnicity: 111 (90%) White | Standard systemic Azathioprine, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, sulfasalazine and tacrolimus Targeted Abatacept, adalimumab, belimumab, certolizumab, etanercept, infliximab, ixekizumab rituximab, tocilizumab, tofacitinib, ustekinumab | BNT162b2 (64/123, 52%) mRNA-1273 (59/123, 48%) | Humoral Seroconversion 91/123 (74%) of individuals with rheumatological diseases had detectable antibodies 18–26 days post-vaccine 55/85 (65%) individuals receiving standard immune-modifying therapy had detectable antibodies vs 16/17 (94%) individuals receiving TNFi A lower proportion of individuals receiving rituximab (2/6, 33%) had an antibody response vs those receiving methotrexate (10/13, 77%) or TNFi (16/17, 94%) | N/A |
Braun-Moscovici et al. [23] | Rheumatological disease (n = 264) including RA, PsA, SpA, sarcoidosis, SLE, systemic sclerosis, myositis, Sjogren’s syndrome, myositis and vasculitis Individuals recovered from COVID-19 (n = 26) | Mean age: Rheumatological disease – 58 years Recovered from COVID-19 – 47 years Gender: Rheumatological disease – 200 (76%) female Recovered from COVID-19 – 19 (73%) female Ethnicity: Not included | Standard systemic Azathioprine, ciclosporin, corticosteroids, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, Purinethol and salazopurine Targeted Abatacept, adalimumab, anakinra, baricitinib, belimumab, certolizumab, etanercept, golimumab, infliximab, ixekizumab, JAKi, mepolizumab, risankizumab, rituximab, sarilumab, secukinumab, tocilizumab, tofacitinib, upadacitinib and ustekinumab | BNT162b2 | N/A | Humoral Seroconversion 68/78 (87%) methotrexate-treated individuals, 24/48 (50%) rituximab-treated individuals and 63/63 (100%) individuals on TNFi had detectable antibodies 4–6 weeks following the 2nd dose Neutralisation 227/264 (86%) individuals with rheumatological disease had detectable neutralising antibodies 4–6 weeks following the 2nd dose. 23/47 (49%) individuals on rituximab had detectable neutralising antibodies vs 5/8 (63%) individuals on abatacept, 17/21 (81%) individuals on mycophenolate mofetil and 4/5 (80%) individuals on IL-17i. Neutralising titres were higher in vaccinated individuals vs individuals with rheumatological disease who had recovered from COVID-19 (p < 0.05) |
Bugatti et al. [24] | Rheumatological disease (n = 140) including RA, PsA, SpA No controls | Mean age: 56 years Gender: 95 (67.9%) female Ethnicity: Not included | Standard systemic Ciclosporin, leflunomide, methotrexate, prednisone and sulfasalazine, Targeted Cytotoxic T lymphocyte associated protein-4 immunoglobulin (CTLA4Ig), IL-6Ri, IL-17/IL-23i, JAKi, PDE4i and TNFi | BNT162b2 | Humoral Seroconversion 85/140 (60%) individuals had detectable antibodies after 21 days. Use of methotrexate, glucocorticoids and CTLA4Ig was more common, and use of IL-17/23 inhibitors was less common, in individuals who did not mount detectable antibodies Seroconversion decreased from 85.4% among patients not on methotrexate or glucocorticoids to 33.3% among those on both therapies | N/A |
Chen et al. [25] | IMIDs including RA, SLE, PsA, multiple sclerosis, ankylosing spondylitis, Sjögren’s syndrome, Hashimoto’s disease, psoriasis, combined variable immune deficiency, vasculitis, scleroderma, ANCA-associated vasculitis, IBD, alopecia areata, asthma and inflammatory arthritis (n = 75) Healthy controls (n = 25) | Median age: 49 years Gender: 52 (68%) female Ethnicity: 69 (90%) White, 5 (6%) Black, 1 (1%) Asian Demographics for controls not included | Standard Systemic Sulfasalazine, antimetabolites, systemic steroids Targeted anti-CD20, IL-23i and TNFi | BNT162b2 | N/A | Humoral Seroconversion Individuals receiving anti-CD20 had substantially lower levels of spike-specific IgG vs controls at 3 months post second dose. Most other drug treatment groups showed no statistically significant differences in spike-specific IgG titres vs controls Neutralisation 48/75 (64%) individuals with IMIDs on immune-modifying therapy developed adequate neutralization titres against Delta variant vs 23/25 (92%) healthy controls at 3 months post vaccine. 8/12 (67%) individuals on TNFi developed adequate neutralization titres compared to 2/9 (22%) on IL-23i and 4/12 (33%) on antimetabolites |
Dailey et al. [26] | IBD (n = 436) including Crohn’s disease, ulcerative colitis and IBD-unspecified. Only 33 were analysed post vaccination Adult and paediatric controls (number or other details not specified) | Mean age: 17 years Gender: 183 (42%) female Ethnicity: Not included | Standard systemic Corticosteroids and methotrexate Targeted Infliximab, vedolizumab | BNT162b2 (21/33, 63.6%) mRNA-1273 (7/33, 21.2%) Ad26.COV2-S (5/33, 15.2%) | N/A | Humoral Seroconversion Spike-specific IgG responses were higher (~ 15 ×) following vaccination vs natural infection in the IBD subgroup between 3.1 and 3.3 weeks post 2nd dose (p < 0.0001) Neutralising All IBD subjects had higher (~ 10 ×) neutralising titres (against SARS-CoV-2 wild type [WT] or mutant [mt S-RBD] spike protein receptor binding domain) post 2nd vaccination vs those with history of natural infection, including patients receiving infliximab monotherapy or infliximab/methotrexate co-therapy |
Deepak et al. [27] | IMIDs including RA, spondyloarthritis, uveitis, SLE, vasculitis, Sjogren syndrome, multiple sclerosis and IBD (n = 133) Healthy controls (n = 53) | Mean age: IMIDs – 45 years Healthy controls – 43 years Gender: IMIDs – 99 (74.4%) female Healthy controls – 29 (54.7%) female Ethnicity: IMIDs – 117 (88.0%) White, 9 (6.8%) Asian, 4 (3.0%) Black or African American, 3 (2.3%) others Healthy controls – 42 (79.2%) White, 7 (13.2%) Asian, 1 (1.9%) Black or African American, 3 (5.7%) other | Standard systemic Azathioprine, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, sulfasalazine and tacrolimus Targeted Adalimumab, certolizumab, etanercept, golimumab, guselkumab, infliximab, ocrelizumab, rituximab and ustekinumab | BNT162b2 mRNA-1273 Number of individuals receiving specific vaccines not given | N/A | Humoral Seroconversion 118/133 (89%) individuals with IMIDs vs all healthy controls (53/53, 100%) seroconverted within 14–20 days post-vaccination. No difference between individuals with IMIDs on standard immune-modifying therapy vs those not on standard immune-modifying therapy 6/10 (60%) individuals with IMIDs receiving rituximab/ocrelizumab seroconverted Neutralising Neutralisation titres against the common variant (D614G) were 2391 (95% CI 1537 to 3719) in individuals with IMIDs on standard immune-modifying therapy vs 2270 (95% CI, 1650 to 3121) in those not on standard therapy at 20 days post-vaccination Individuals with IMIDs on rituximab/ocrelizumab had lower neutralisation titres vs individuals with IMIDs who were not on rituximab/ocrelizumab (neutralisation titres 723 (95% CI 233 - 2246) vs 2445 (95% CI 1890 - 3164), respectively) |
Furer et al. [28] | Rheumatological disease including RA, PsA, axial spondyloarthritis, SLE, systemic vasculitis, large vessel vasculitis (n = 686) Healthy controls (n = 121) | Median age: Rheumatological disease – 59 years Healthy controls – 50 years Gender: Rheumatological disease – 475 (69.3%) female Healthy controls – 78 (65%) female Ethnicity: Not mentioned | Standard systemic Glucocorticoids, hydroxychloroquine, leflunomide, methotrexate and mycophenolate mofetil Targeted Abatacept, IL-6i, IL-17i, JAKi, rituximab and TNFi | BNT162b2 | N/A | Humoral Seroconversion 590/686 (86%) patients with rheumatological diseases seroconverted vs 100% controls (p < 0.0001), 2–6 weeks after the second vaccination Compared to individuals receiving biologic monotherapy, those on methotrexate monotherapy or methotrexate in combination with other treatments had reduced seroconversion rates (> 97% vs 92%, p = 0.02 or 84%, p < 0.0001, respectively) Rituximab impaired seroconversion (39%) Spike specific IgG titres were significantly lower in individuals with rheumatological diseases compared with controls |
Geisen et al. [29] | IMIDs including psoriasis, IBD, SLE, RA, spondyloarthropathy, PsA (n = 26) Healthy controls (n = 42) | Mean age: IMIDs – 51 years Healthy controls – 38 years Gender: IMIDs – 17 (64.3%) female Healthy controls – 29 (69.2%) female Ethnicity: Not included | Standard systemic Azathioprine, leflunomide, hydroxychloroquine and sulfasalazine Targeted Adalimumab, belimumab, certolizumab, etanercept, golimumab, infliximab, ixekizumab, secukinumab, tocilizumab, ustekinumab and vedolizumab | BNT162b2 (63/68, 92.6%) mRNA-1273 (5/68, 7.4%) | N/A | Humoral Seroconversion Spike specific IgG was detected in all individuals Lower titres were detected in individuals with IMIDs vs healthy controls (mean titre 2053 BAU/mL vs 2685 BAU/mL, p = 0.037) at 7 days post- second dose. No significant difference between standard immune-modifying therapy, TNFi and IL-17i Neutralising Individuals with IMIDs on immune-modifying therapy had lower levels of neutralising antibodies vs healthy controls (mean inhibitory level 87.42% vs 96.04%, p = 0.044) |
Haberman et al. [30] New York Cohort | IMIDs including psoriasis, PsA, RA, vasculitis, dermatomyositis, adult-onset Still’s disease, sarcoidosis, PMR (n = 51) Healthy controls (n = 26) New York Cohort | Mean age: IMIDs, not on methotrexate – 49 years IMIDs, on methotrexate – 63 years Healthy controls – 49 years Gender: IMIDs, not on methotrexate – 18 (69.2%) female IMIDs on methotrexate – 18 (66.7%) female Healthy controls – 16 (61.5%) female Ethnicity: IMIDs, not on methotrexate – 20 (76.9%), 2 (7.7%) Black, 3 (11.5%) Asian, 3 (11.5%) Hispanic IMIDs, on methotrexate – 17 (63%) White, 3 (11.1%) Black, 3 (11.1%) Asian, 5 (18.5%) Hispanic Healthy controls – 16 (61.5%) White, 1 (3.8%) Black, 9 (34.6%) Asian, 1 (3.8%) Hispanic | Standard systemic Hydroxychloroquine, leflunomide, methotrexate, oral steroids, sulfasalazine Targeted Abatacept, apremilast, IL-17i, IL-23i, JAKi, rituximab and TNFi | BNT162b2 | N/A | Humoral Seroconversion 18/25 (72.0%) of IMID cohort on methotrexate had detectable antibodies vs 24/26 (92.3%) not on methotrexate (p = 0.045). 25/26 (96.1%) healthy controls had detectable antibodies Timing of sampling not specified Cellular Spike-specific B cells, activated CD4 + T cells and circulating T follicular helper cells were similarly induced in all groups Activated CD8+ T-cell responses were attenuated in methotrexate-treated group vs healthy controls or individuals with IMIDs not receiving methotrexate |
Haberman et al. [30] Erlangen cohort | IMIDs including psoriasis, PsA, RA, vasculitis, dermatomyositis, adult-onset Still’s disease, sarcoidosis, PMR (n = 31) Healthy controls (n = 182) Erlangen cohort | Mean age: IMIDs, not on methotrexate – 45 years IMIDs, on methotrexate – 55 years Healthy controls – 41 years Gender: IMIDs, not on methotrexate – 7 (58.3%) female IMIDs, on methotrexate – 15 (75.0%) female Healthy controls – 104 (57.1%) female Ethnicity: IMIDs, not on methotrexate–11 (100%) White IMIDs, on methotrexate – 19 (95%) White and 1 (5%) Asian Healthy controls – 178 (97.8%) White, 2 (1.1%) Asian, 1 (0.6%) Hispanic | Standard systemic Methotrexate Targeted TNFi | BNT162b2 | N/A | Humoral Seroconversion 10/11 (90.9%) patients not on methotrexate, and 10/20 (50.0%) patients receiving methotrexate had detectable antibodies vs 179/182 (98.3%) healthy controls Timing of sampling not specified |
Kappelman et al. [31] | IBD (n = 317) No controls | Mean age: 51 years Gender: 238 (75%) female Ethnicity: 301 (95%) White, 5 (2%) Asian | Standard systemic 6-mercaptopurine, azathioprine, budesonide, methotrexate and sulfasalazine Targeted TNFi, ustekinumab and vedolizumab | BNT162b2 (173/317, 55%) mRNA-1273 (144/317, 45%) | N/A | Humoral Seroconversion 300/317 (94.6%) had detectable antibodies at 64 days post-2nd vaccination. 11/13 (85%) individuals taking corticosteroids had detectable antibodies vs 289/304 (95%) non-steroid users 19/20 (95%) individuals on standard immune-modifying therapy had detectable antibodies vs 101/108 (94%) individuals on TNFi monotherapy |
Kennedy et al. [32] | IBD including Crohn’s disease, ulcerative colitis or IBD unclassified who have received one dose of vaccination (n = 1293) and two doses (n = 27) No healthy controls | Mean age: Overall – 44 years Infliximab – 41 years Vedolizumab – 49 years Gender: Overall – 634 (49.2%) female Infliximab – 434 (50.3%) female Vedolizumab – 200 (47.1%) female Ethnicity: Overall – 1172 (91.1%) White, 78 (6.1%) Asian, 24 (1.9%) mixed, 8 (0.6%) Black Infliximab – 791 (91.8%) White, 46 (5.3%) Asian, 16 (1.9%) mixed, 6 (0.7%) Black Vedolizumab – 381 (89.9%) White, 32 (7.5%) Asian, 8 (1.9%) mixed, 2 (0.5%) Black | Targeted Infliximab and vedolizumab | BNT162b2 (589/1293, 45.6%) ChAdOx1 nCoV-19 (704/1293, 54.4%) | Humoral Seroconversion Spike-specific IgG titres were lower in patients treated with infliximab vs vedolizumab, at 3–10 weeks following BNT162b2 (6.0 U/mL vs 28.8 U/mL, p < 0.0001) or ChAdOx1 nCoV-19 (4.7 U/mL vs 13.8 U/mL, p < 0.0001) | Humoral Seroconversion 17/20 (85%) infliximab-treated individuals and 6/7 (86%) vedolizumab-treated individuals seroconverted at 3–10 weeks post-vaccination (p = 0.68) |
Mahil et al. [33•] | Psoriasis (n = 84) Healthy controls (n = 17) | Median age: Methotrexate – 48 years TNFi–36 years IL-17i – 45 years IL-23i – 50 years Healthy controls – 34 years Gender: Methotrexate – 6 (35%) female TNFi – 14 (52%) female IL-17i – 7 (47%) female IL-23i – 10 (40%) female Healthy controls – 8 (47%) female Ethnicity: Methotrexate – 13 (76%), 1 (6%) Black, 3 (18%) South Asian TNFi – 24 (89%), 3 (11%) South Asian IL-17i – 13 (87%) White, 2 (13%) South Asian IL-23i – 21 (84%) White, 3(12%) South Asian, 1 (4%) mixed Healthy controls – 14 (82%) White, 3 (18%) South Asian | Standard systemic Methotrexate Targeted Adalimumab, certolizumab, etanercept, guselkumab, infliximab, ixekizumab, risankizumab secukinumab and ustekinumab | BNT162b2 | Humoral Seroconversion 60/77 (78%) individuals receiving immune-modifying therapy vs 17/17 (100%) healthy controls seroconverted, at 28 days post-vaccine Individuals receiving methotrexate (7/15, 47%) had a lower seroconversion rate vs individuals receiving biologics including TNFi (19/24, 79%), IL-17i (15/15, 100%) and IL-23i (19/23, 83%) Neutralising Individuals receiving TNFi, IL-17i, and IL-23i had similar neutralisation titres against wild-type SARS-CoV-2 vs controls. Patients on methotrexate had lower neutralisation titres (median ID50 129 [IQR 40–236]) vs patients on biologics (269 [141–418], p = 0·011) or healthy controls (317 [213–487], p = 0.0032) Cellular T-cell response rates were similar in patients receiving methotrexate, biologics, and controls at 28 days post-vaccine | N/A |
Mahil et al. [34•] | Psoriasis (n = 67) Healthy controls (n = 15) | Median age: Methotrexate – 50 years TNFi – 36 years IL-17i – 43 years IL-23i – 51 years Healthy controls – 38 years Gender: Methotrexate – 6 (43%) female TNFi – 11 (58%) female IL-17i – 7 (50%) female IL-23i – 8 (40%) female Healthy controls – 7 (47%) female Ethnicity: Methotrexate – 11 (79%) White, 1 (7%) Black, 2 (14%) South Asian TNFi – 18 (95%) White, 1 (5%) South Asian IL-17i – 12 (86%) White, 2 (14%) South Asian IL-23i – 17 (85%) White, 2 (10%) South Asian, 1 (5%) mixed Healthy controls – 13 (87%) White, 2 (13%) South Asian | Standard systemic Methotrexate Targeted IL-17i, IL-23i and TNFi | BNT162b2 | N/A | Humoral Seroconversion All participants seroconverted 14 days post-second vaccine The second vaccine boosted spike-specific IgG titres in all groups, with no significant differences between patients receiving immune-modifying therapy (median EC50 1816 [IQR 641–3645]) vs healthy controls (2749 [867–4770], p = 0·14). Median titres were lowest in individuals on methotrexate (median EC50 1751 [IQR 468–4976]) vs patients on biologics (1816 [787–3534], p = 0·65) or healthy controls (2749 [867–4770], p = 0·20) Neutralising All participants had detectable neutralising antibodies against wild-type, Alpha, and Delta variants post-second vaccine. All groups showed increased neutralising antibody titres post-second vs first dose. Individuals on methotrexate had similar neutralisation activity against the Alpha variant (ID50 440 [IQR 101–935]) vs those receiving biologics (453 [233–955], p = 0·97) or healthy controls (491 [264–1227], p = 0·63). Neutralisation activity against the Delta variant was similar across all groups i.e. individuals on methotrexate (ID50 856 [77–1476]), biologics (469 [232–1309], p = 0·76) and controls (863 [225–1297], p = 0·49) Cellular Those on methotrexate had lower induction of T-cell responses vs healthy controls. A lower proportion of patients receiving methotrexate had detectable T-cell responses (8/13, 62% [95%CI 32–86]) vs those on biologics (37/50, 74% [95%CI 60–85], p = 0·38) or controls (14/14, 100% [95%CI 77–100], p = 0·022) |
Moor et al. [35] | Patients including ANCA-associated vasculitis, RA, Sjogren’s syndrome, SLE, multiple sclerosis, pemphigus vulgaris, systemic sclerosis and pemphigoid (n = 96) Healthy controls (n = 29) | Median age: Patients – 67 years Healthy controls – 54 years Gender: Patients – 51 (53%) female Healthy controls – 19 (66%) female Ethnicity: Not included | Targeted Ocrelizumab or rituximab | BNT162b2 (58/96, 60%) mRNA-1273 (38/96, 40%) | N/A | Humoral Seroconversion Detectable antibodies in 47/96 (49%) patients on rituximab/ocrelizumab at 1·79 months post-second vaccine dose, vs 29/29 (100%) controls at 1·81 months (p < 0·001) Cellular SARS-CoV-2-specific IFNγ responses detected in 14/44 (32%) patients on rituximab/ocrelizumab vs 22/25 (88%) healthy controls (p < 0·001) |
Rubbert-Roth et al. [36] | RA (n = 53) Healthy controls (n = 20) | Mean age: RA – 65 years Healthy controls – 45 years Gender: RA – 29 (54.7%) female Healthy controls – 14 (70%) female Ethnicity: Not included | Standard systemic Leflunomide, methotrexate and prednisone Targeted Anti-cytokine drugs (specific drugs not mentioned), abatacept, JAKi | BNT162b2 (64/73, 87.7%) mRNA-1273 (9/73, 12.3%) | Humoral Seroconversion 5/51 (10%) individuals with RA on immune-modifying therapy had detectable antibodies post-vaccine vs 18/20 (90%) controls (p < 0·001) Spike specific IgG titres were lower in patients with RA on immune-modifying therapy (median 0.4 U/ml, IQR 0.4–2.13) vs healthy controls (99.2 U/ml, 24.8–172, p < 0.0001) at 3 weeks post-vaccination | Humoral Seroconversion Spike specific IgG titres were lower in individuals with RA (657 U/ml, IQR 188–2500) vs healthy controls (2500 U/ml, IQR 2500–2500, p < 0.0001) at 2 weeks after the second vaccination 45/51 (88%) individuals with RA on immune-modifying therapy had detectable antibody titres post-second vaccine. Of 6 individuals who did not have detectable antibodies, 4 were receiving JAKi monotherapy or combination therapy, 1 methotrexate/prednisolone co-therapy and 1 methotrexate/prednisolone co-therapy. Neutralising A neutralising humoral response was detected in 13/16 (81%) individuals on standard systemic therapy, 17/18 (94%) on cytokine targeted biologic therapy, 4/5 (80%) on abatacept, and 8/12 (67%) on JAKi therapy |
Ruddy et al. [37] | Rheumatological disease (n = 404) including RA, ankylosing spondylitis, PsA, reactive arthritis, SLE, Sjogren’s syndrome, myositis, systemic sclerosis and vasculitis No controls | Median age: 44 years Gender: 385 (96%) female Ethnicity: 367 (91%) White | Standard systemic Azathioprine, ciclosporin, dimethyl fumarate, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, sirolimus, sulfasalazine and tacrolimus Targeted Abatacept, anakinra, belimumab, guselkumab, IL-6i, IL-17i, JAKi, rituximab, TNFi and ustekinumab | BNT162b2 (198/404, 49%) mRNA-1273 (204/404, 51%) | N/A | Humoral Seroconversion 378/404 (94%) of individuals with rheumatological disease seroconverted at a median of 29 days after 2nd dose A greater proportion of those receiving TNFi had detectable antibodies (100%), vs those receiving mycophenolate (73%, p < 0.001), rituximab (26%, p < 0.001) or glucocorticoids (82%, p < 0.001) or those with a diagnosis of myositis (79%, p = 0.01) Lower median antibody titres in individuals receiving mycophenolate mofetil (8 U/mL) and rituximab (< 0.4 U/mL) vs individuals receiving glucocorticoid monotherapy (> 250 U/mL) |
Seree-aphinan et al. [38] | Cases: Individuals with pemphigus, psoriasis and chronic spontaneous urticaria who are receiving immune-modifying therapy (n = 14) Controls: individuals (with acne, melasma, androgenetic alopecia, seborrheic keratosis) who are not receiving immune-modifying therapy (n = 18) | Mean age: Controls – 45 years Cases – 44 years Gender: Controls – 11 (61%) female Cases – 10 (71%) female Ethnicity: Not included | Standard systemic Azathioprine, ciclosporin, methotrexate, mycophenolate mofetil and prednisone Targeted Ixekizumab, omalizumab and secukinumab | CoronaVac (Sinovac) | N/A | Humoral Seroconversion No individuals (0/6, 0%) taking azathioprine, ciclosporin, mycophenolate mofetil, or moderate-to-high dose corticosteroids seroconverted 4 weeks post-second vaccine. 7/8 (87.5%) individuals on low dose methotrexate, low dose systemic corticosteroids, or biologics seroconverted Neutralising Patients on azathioprine, ciclosporin, mycophenolate mofetil, or moderate-to-high dose corticosteroids had lower neutralizing activity vs those receiving low dose methotrexate, low dose systemic corticosteroids or biologics |
Seyahi et al. [39] | IMIDs (n = 104) including RA, SLE, Sjogren’s syndrome, polymyositis, ankylosing spondylitis, PsA or psoriasis, Behcet’s syndrome, vasculitis, Familial Mediterranean Fever, IBD. This cohort comprises hospital workers (n = 82) and elderly individuals aged 65 and above (n = 22) Healthy controls (n = 347), comprising hospital workers (n = 300) and elderly individuals (n = 47) | Mean age: Hospital workers with IMIDs – 42 years Elderly group with IMIDs – 71 years Control hospital workers – 71 years, Control elderly group – 71 years Gender: Hospital workers with IMIDs – 53 (64.6%) female Elderly group with IMIDs – 16 (72.7%) female Control hospital workers – 193 (64.3%) female Control elderly group – 24 (51.1%) female Ethnicity: Not included | Standard systemic Azathioprine, leflunomide, methotrexate mycophenolate mofetil, prednisone, sulfasalazine and tacrolimus Targeted Anakinra, interferon-alpha, rituximab, secukinumab, TNFi and tocilizumab | CoronaVac (Sinovac) | N/A | Humoral Seroconversion A lower proportion of hospital workers with IMIDs had detectable antibodies vs hospital worker controls (92.7% vs 99.7%, p < 0.001) at least 21 days following the second vaccination. A lower proportion of elderly individuals with IMIDs had detectable antibodies vs elderly controls (77.3% vs 97.9%, p = 0.011) at least 21 days post-second vaccine A lower proportion of individuals receiving rituximab (1/7, 14.3%) had detectable antibodies vs those receiving other targeted therapy (22/25, 88%), standard therapy (25/27, 92.6%) or no treatment (29/29, 100%) |
Simon et al. [40] | IMIDs including SpA, RA, IBD, psoriasis, SLE, systemic sclerosis, IgG4-related diseases, GCA, periodic fever syndromes, granulomatosis with polyangiitis and polymyalgia rheumatica (n = 84) Healthy controls (n = 182) | Mean age: IMIDs – 53 years Healthy cohort – 41 years Gender: IMIDs – 55 (65.5%) female Healthy controls–104 (57.1%) female Ethnicity: Not included | Standard systemic Hydroxychloroquine, methotrexate, sulfasalazine Targeted IL-17/23i, JAKi and TNFi | BNT162b2 | Humoral Seroconversion 79/84 (94%) individuals with IMIDs on immune-modifying therapy vs 182/182 controls (100%) had detectable antibodies at 11 days post-vaccine (p = 0.003) | Humoral Seroconversion 79/84 (94%) individuals with IMIDs on immune-modifying therapy vs all (100%) controls had detectable antibodies up to 39 days post-second vaccine (p = 0.003). No difference between individuals with IMIDs on standard or targeted therapy or no treatment Neutralising 76/84 (90.5%) individuals with IMIDs on immune-modifying therapy vs 181/182 (99.5%) controls had neutralising antibodies (p = 0.0008) |
Wieske et al. [41] | IMIDs on immune-modifying therapy, including vasculitis, Sjogren’s syndrome, PMR, GCA, vitiligo, pemphigus, psoriasis, auto-immune hepatitis, auto-immune sclerosing cholangitis, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, inflammatory myositis, neuromyelitis optica spectrum disorder (n = 1692) IMIDs not on immune-modifying therapy (n = 419) Healthy controls (n = 174) | Mean age: 50 years overall Gender: 1470 (62.8%) female overall Ethnicity: Not included | Standard systemic Ciclosporin, hydroxychloroquine, methotrexate, mycophenolate mofetil and sulfasalazine Targeted Abatacept, anti-CD20, belimumab, dupilumab, JAKi, IL-17i, IL-23i, interferon-beta, natalizumab, omalizumab, tocilizumab, TNFi, ustekinumab and vedolizumab Others: Intravenous or subcutaneous immunoglobulin, purine antagonists, and sphingosine-1-phosphate receptor modulators | ChAdOx1 nCoV-19 (254/2339, 11%) BNT162b2 (1324/2339, 57%) mRNA-1273 (712/2339, 30%) Ad.26.COV2.S (49/2339, 2%) | N/A | Humoral Seroconversion 39/128 (30·5%) on anti-CD20 therapy seroconverted vs 479/493 (97·2%) controls Compared with controls, relative risk of seroconversion post-second vaccine on anti-CD20 therapy was 0.32 (95% CI 0·19–0·49), while the relative risks for other immune-modifying drugs were not significantly reduced For those who seroconverted, anti-CD20 was associated with substantial reductions in antibody titres. TNFi, dupilumab, intravenous and subcutaneous immunoglobulin, and methotrexate were associated with moderate reductions in antibody titres Neutralisation Neutralisation capacity of individuals on immune-modifying monotherapy was similar to controls |
Wong et al. [42] | IBD (n = 48) Vaccinated healthcare workers (HCWs, n = 14) Healthy controls (n = 29) | Mean age: IBD – 49 years HCWs – 35 years Healthy controls – 32 years Gender: IBD – 25 (52%) female HCWs -7 (50%) female Healthy controls – 11 (37.9%) female Ethnicity: IBD – 42 (87.5%) White HCWs – 10 (71.4%) White Healthy controls – 18 (62.1%) White | Targeted Guselkumab, TNFi, vedolizumab and vedolizumab with thiopurine | BNT162b2 (54/91, 59.3%) mRNA-1273 (37/91, 40.7%) | N/A | Humoral Seroconversion 26/26 (100%) individuals with IBD on targeted therapy had detectable antibodies at 8–18 days post-second vaccine. Vedolizumab was associated with lower spike specific IgG titres vs controls (p = 0.0043) |