Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthritis receiving baricitinib: results from a long-term extension trial substudy
Open accessAbstract
BACKGROUND: Clinical guidelines recommend pneumococcal and tetanus vaccinations in patients with rheumatoid arthritis (RA). Baricitinib is an oral, selective Janus kinase (JAK) 1/JAK 2 inhibitor and is approved for the treatment of moderately to severely active RA in adults in over 50 countries including European countries, the USA, and Japan. This substudy evaluated pneumococcal conjugate and tetanus toxoid vaccine (TTV) responses in patients with RA receiving baricitinib. These vaccines elucidate predominantly T cell-dependent humoral antibody response. METHODS: Eligible RA patients receiving baricitinib 2 mg or 4 mg with or without concomitant methotrexate (MTX) were enrolled in a phase 3 long-term extension trial (RA-BEYOND; ClinicalTrials.gov, NCT01885078) in USA/Puerto Rico. Patients were vaccinated with 13-serotype pneumococcal conjugate vaccine (PCV-13) and TTV. Primary endpoints were the proportion of patients achieving a satisfactory humoral response for PCV-13 (≥ 2-fold increase in anti-pneumococcal antibody concentrations in ≥ 6 serotypes) and TTV (≥ 4-fold increase in anti-tetanus concentrations) at 5 weeks post-vaccination. Secondary endpoints included humoral responses at 12 weeks and functional responses of serotypes 4, 6B, 14, and 23F (twofold and fourfold increases in opsonic indexes at 5 and 12 weeks). RESULTS: Of 106 patients with a mean duration of RA of approximately 12 years, 80% were female, 30% were taking corticosteroids, and 89% (N = 94) were taking baricitinib plus MTX; most patients (97% PCV-13/96% TTV) completed the evaluations. Overall, 68% (95% CI 58.4, 76.2) of patients achieved a satisfactory response to PCV-13, 43% (34.0, 52.8) achieved a ≥ 4-fold increase in anti-tetanus concentrations, and 74% (64.2, 81.1) achieved a ≥ 2-fold increase. PCV-13 response was similar for patients taking corticosteroids (71%; 53.4, 83.9) vs those not (67%; 55.2, 76.5). The percentage of sera with a ≥ 2-fold increase in post-vaccination opsonic indexes at week 5 ranged from 47% (serotype 14) to 76% (serotype 6B). Through 12 weeks post-vaccination, seven patients (6.6%) reported injection-site events. There were no deaths during the substudy, and three patients experienced a serious adverse event. CONCLUSIONS: Approximately two thirds of patients on long-term baricitinib achieved satisfactory humoral and functional responses to PCV-13 vaccination, while TTV responses were less robust. PCV-13 response was not diminished in those taking concomitant corticosteroids. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01885078 . Registered on 24 June 2013.
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RA patients treated with baricitinib achieved a considerable pneumococcal humoral response.
“A considerable pneumococcal humoral response was achieved in patients with RA treated with baricitinib.33”
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Cites
2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis
Singh, J. A., Saag, K. G., Bridges, S. L., Akl, E. A., Bannuru, R. R., Sullivan, M. C., Vaysbrot, E. E., McNaughton, C., Osani, M. C., Shmerling, R. H., et al. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39480 · Cited by 2,806 · see citing works
2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis
Singh, J. A., Saag, K. G., Bridges, S. L., Akl, E. A., Bannuru, R. R., Sullivan, M. C., Vaysbrot, E. E., McNaughton, C., Osani, M. C., Shmerling, R. H., et al. (2015) · Arthritis Care & Research · doi:10.1002/acr.22783 · Cited by 1,113 · see citing works
Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis
Taylor, P. C., Keystone, E. C., van der Heijde, D. M. F. M., Weinblatt, M. E., Morales, L., Gonzaga, J. R., Yаkushin, S. S., Ishii, T., Emoto, K., Beattie, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1608345 · Cited by 951 · see citing works
JAKs and STATs in immunity, immunodeficiency, and cancer
O'Shea, J. J., Holland, S. M., & Staudt, L. M. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1202117 · Cited by 927 · see citing works
Ramiro, S., Gaujoux-Viala, C., Nam, J. L., Smolen, J. S., Buch, M. H., Gossec, L., van der Heijde, D. M. F. M., Winthrop, K. L., & Landewé, R. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204575 · Cited by 701 · see citing works
Self-citationBaricitinib in Patients with Refractory Rheumatoid Arthritis
Genovese, M. C., Kremer, J. M., Zamani, O., Ludivico, C. L., Krogulec, M., Xie, L., Beattie, S. D., Koch, A. E., Cardillo, T. E., Rooney, T. P., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1507247 · Cited by 632 · see citing works
Fridman, J. S., Scherle, P., Collins, R. J., Burn, T. C., Li, Y., Li, J., Covington, M. B., Thomas, B. A., Collier, P., Favata, M. F., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902819 · Cited by 472 · see citing works
Bingham, C. O., Looney, R. J., Deodhar, A., Halsey, N., Greenwald, M., Codding, C., Trzaskoma, B., Martin, F., Agarwal, S., & Kelman, A. (2010) · Arthritis & Rheumatism · doi:10.1002/art.25034 · Cited by 459 · see citing works
Self-citationFleischmann, R., Schiff, M. H., van der Heijde, D. M. F. M., Ramos-Remus, C., Spindler, A. J., Stanislav, M., Zerbini, C. A. F., Gurbuz, S., Dickson, C. L., de Bono, S., et al. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39953 · Cited by 429 · see citing works
Dougados, M., van der Heijde, D. M. F. M., Chen, Y., Greenwald, M., Drescher, E., Liu, J., Beattie, S. D., Witt, S., de la Torre, I., Gaich, C. L., et al. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-210094 · Cited by 405 · see citing works
Ramiro, S., Sepriano, A. R., Chatzidionysiou, K., Nam, J. L., Smolen, J. S., van der Heijde, D. M. F. M., Dougados, M., van Vollenhoven, R., Bijlsma, J. W. J., Burmester, G. R., et al. (2017) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-210708 · Cited by 358 · see citing works
The Risk of Infections with Biologic Therapies for Rheumatoid Arthritis
Fürst, D. E. (2009) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2008.10.002 · Cited by 291 · see citing works
The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis
Winthrop, K. L., Silverfield, J., Racewicz, A., Neal, J., Lee, E. B., Hrycaj, P., Gomez-Reino, J., Soma, K., Mebus, C., Wilkinson, B., et al. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-207191 · Cited by 196 · see citing works
Self-citationPneumococcal vaccine and opsonic pneumococcal antibody
Song, J. Y., Moseley, M. A., Burton, R. L., & Nahm, M. H. (2013) · Journal of Infection and Chemotherapy · doi:10.1007/s10156-013-0601-1 · Cited by 155 · see citing works
Vaccines: Vaccination in Patients with Chronic Rheumatic or Autoimmune Diseases
Glück, T., & Müller‐Ladner, U. (2008) · Clinical Infectious Diseases · doi:10.1086/587063 · Cited by 148 · see citing works
Kapetanovic, M. C., Roseman, C., Jonsson, G. G., Truedsson, L., Saxne, T., & Geborek, P. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30580 · Cited by 147 · see citing works
Crnkic Kapetanovic, M., Saxne, T., Jönsson, G., Truedsson, L., & Geborek, P. (2013) · Arthritis Research & Therapy · doi:10.1186/ar4358 · Cited by 142 · see citing works
Bingham, C. O., Rizzo, W., Kivitz, A., Hassanali, A., Upmanyu, R., & Klearman, M. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-204427 · Cited by 108 · see citing works
Self-citationKim, D. K., Bridges, C. B., & Harriman, K. H. (2016) · Annals of Internal Medicine · doi:10.7326/m15-3005 · Cited by 102 · see citing works
Gandolfo, S., Fabro, C., Bulfoni, M., et al. (2017) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2017-eular.6450 · Cited by 88 · see citing works
Burton, R. L., & Nahm, M. H. (2012) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00086-12 · Cited by 81 · see citing works
Daly, T. M., & Hill, H. R. (2014) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00735-14 · Cited by 71 · see citing works
Migita, K., Akeda, Y., Akazawa, M., Tohma, S., Hirano, F., Ideguchi, H., Kozuru, H., Jiuchi, Y., Matsumura, R., Suematsu, E., et al. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0863-3 · Cited by 64 · see citing works
Measuring immune responses to pneumococcal vaccines
LaFon, D. C., & Nahm, M. H. (2018) · Journal of Immunological Methods · doi:10.1016/j.jim.2018.08.002 · Cited by 64 · see citing works
Kim, D.-K., Bridges, C. B., & Harriman, K. H. (2016) · American Journal of Transplantation · doi:10.1111/ajt.13877 · Cited by 62 · see citing works
Kapetanovic, M. C., Roseman, C., Jonsson, G. G., & Truedsson, L. (2011) · Clinical Rheumatology · doi:10.1007/s10067-011-1856-5 · Cited by 50 · see citing works
Kapetanovic, M., Nagel, J., Nordström, I., Saxne, T., Geborek, P., & Rudin, A. (2017) · Vaccine · doi:10.1016/j.vaccine.2016.12.068 · Cited by 50 · see citing works
van Deursen, A. M. M., van Houten, M. A., Webber, C., Patton, M., Scott, D. A., Patterson, S., Sidhu, M. S., Drews, W., Gruber, W. C., Emini, E. A., et al. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/cix419 · Cited by 49 · see citing works
Rákóczi, É., Perge, B., Végh, E., Csomor, P., Pusztai, A., Szamosi, S., Bodnár, N., Szántó, S., Szűcs, G., & Szekanecz, Z. (2016) · Joint Bone Spine · doi:10.1016/j.jbspin.2015.10.017 · Cited by 40 · see citing works
Vaccinations for Rheumatoid Arthritis
Perry, L., Winthrop, K. L., & Curtis, J. R. (2014) · Current Rheumatology Reports · doi:10.1007/s11926-014-0431-x · Cited by 39 · see citing works
Self-citationWinthrop, K. L., Korman, N. J., Abramovits, W., Rottinghaus, S. T., Tan, H., Gardner, A., Mukwaya, G., Kaur, M., & Valdez, H. (2018) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2017.09.076 · Cited by 35 · see citing works
Self-citationDetecting and describing heterogeneity in meta-analysis
Hardy, R. J., & Thompson, S. G. (1998) · Statistics in Medicine · doi:10.1002/(sici)1097-0258(19980430)17:8
Flagged first, then by citations
Research works printed but not linked: 1
- Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998;17:857-72.
- Authors
- Winthrop, K. L., Bingham, C. O., Komocsar, W. J., Bradley, J., Issa, M., Klar, R., & Kartman, C. E.
- Affiliations
- Oregon Health & Science University (US)
- Johns Hopkins University (US)
- Eli Lilly (United States) (US)
- IQVIA (United States) (US)
- Corresponding author
- Winthrop, Kevin L.
- Venue
- Arthritis Research & Therapy
- Published
- 2019-04-18
- Volume
- 21
- Issue
- 1
- Pages
- 102-102
- ISSN
- 1478-6354 (ISSN-L)
- 1478-6362
- PMC
- PMC6471863
- OpenAlex
- W2936505424
- Cited by
- 61
- References
- 32
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 13 · 2021: 20 · 2020: 6 · 2019: 1 · 2018: 1
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Arthritis Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Eli Lilly and Company
- Incyte Corporation
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Keywords
- rheumatoid arthritis, baricitinib, pneumococcal conjugate vaccine, tetanus toxoid vaccine, vaccine response, humoral antibody response, JAK inhibitors, methotrexate, anti-pneumococcal antibodies, anti-tetanus antibodies, opsonic index, vaccine safety, immunogenicity
- MeSH terms
- Aged, Arthritis, Rheumatoid, Azetidines, Female, Humans, Immunity, Cellular, Male, Middle Aged, Purines, Pyrazoles, Streptococcus pneumoniae, Sulfonamides, Tetanus Toxoid, Treatment Outcome, Pneumococcal Vaccines
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