{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:44:55Z","timestamp":1792507495396,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T00:00:00Z","timestamp":1261958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine immunization responses in patients with rheumatoid arthritis (RA) treated with rituximab and to investigate the effects of rituximab\u2010induced CD20+ B cell depletion on immune responses to tetanus toxoid (T cell\u2013dependent antigen), pneumococcal polysaccharide (T cell\u2013independent antigen), and keyhole limpet hemocyanin (KLH) (neoantigen) and on delayed\u2010type hypersensitivity (DTH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a controlled trial, we enrolled 103 patients with active RA receiving a stable dose of methotrexate (MTX). Tetanus toxoid, pneumococcal polysaccharide, and KLH vaccines as well as a\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      skin test were administered to 1 group of patients receiving rituximab plus MTX (called rituximab\u2010treated patients) for 36 weeks and to 1 group of patients receiving MTX alone for 12 weeks. The primary end point was the proportion of patients with a \u22654\u2010fold rise in antitetanus IgG levels. Antitetanus, antipneumococcal, and anti\u2010KLH serum IgG levels were measured prior to and 4 weeks following vaccine administration. The DTH response to\n                      <jats:italic>C albicans<\/jats:italic>\n                      was measured 2\u20133 days following placement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Responses to tetanus toxoid vaccine (\u22654\u2010fold rise) were similar in both groups (39.1% of rituximab\u2010treated patients and 42.3% of patients treated with MTX alone). The ability to maintain a positive DTH response to the\n                      <jats:italic>C albicans<\/jats:italic>\n                      skin test was comparable in both groups (77.4% of rituximab\u2010treated patients and 70% of patients treated with MTX alone), showing no effect of rituximab treatment. Rituximab\u2010treated patients had decreased responses to pneumococcal polysaccharide vaccine (57% of patients had a 2\u2010fold rise in titer in response to \u22651 serotype, compared with 82% of patients treated with MTX alone) and to KLH vaccine (47% of patients had detectable anti\u2010KLH IgG, compared with 93% of patients treated with MTX alone).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Recall responses to the T cell\u2013dependent protein antigen tetanus toxoid as well as DTH responses were preserved in rituximab\u2010treated RA patients 24 weeks after treatment. Responses to neoantigen (KLH) and T cell\u2013independent responses to pneumococcal vaccine were decreased, but many patients were able to mount responses. These data suggest that polysaccharide and primary immunizations should be administered prior to rituximab infusions to maximize responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.25034","type":"journal-article","created":{"date-parts":[[2009,12,28]],"date-time":"2009-12-28T16:05:00Z","timestamp":1262016300000},"page":"64-74","source":"Crossref","is-referenced-by-count":418,"title":["Immunization responses in rheumatoid arthritis patients treated with rituximab: Results from a controlled clinical trial"],"prefix":"10.1002","volume":"62","author":[{"suffix":"III","given":"Clifton O.","family":"Bingham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. John","family":"Looney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul","family":"Deodhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal","family":"Halsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Greenwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Codding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Trzaskoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavius","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariella","family":"Kelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,12,28]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032534"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22025"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21778"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.125.4.1678"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23059"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.2.817"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.1.361"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.077461"},{"key":"e_1_2_7_10_2","article-title":"Long\u2010term safety of patients receiving rituximab in rheumatoid arthritis clinical trials","author":"Van Vollenhoven RF","journal-title":"J Rheumatol."},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/338043"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/3.Supplement_1.S184"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3282ffdeca"},{"key":"e_1_2_7_14_2","first-page":"272","article-title":"Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab","volume":"34","author":"Kaine JL","year":"2007","journal-title":"J Rheumatol"},{"key":"e_1_2_7_15_2","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1182\/blood.V100.6.2257","article-title":"Rituximab treatment results in impaired secondary humoral immune responsiveness","volume":"100","author":"Van der Kolk LE","year":"2002","journal-title":"Blood"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.08.016"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/48.6.B231"},{"key":"e_1_2_7_18_2","unstructured":"Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the advisory committee on immunization practices (ACIP). URL:www.cdc.gov\/mmwr\/preview\/mmwrhtml\/00047135.htm."},{"key":"e_1_2_7_19_2","unstructured":"Centers for Disease Control and Prevention. Recommended adult immunization schedule \u2014 United States 2009. 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