Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthritis receiving baricitinib: results from a long-term extension trial substudy

Abstract

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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“…85 On the other hand, the response appears to improve with second vaccination in studies evaluating influenza 85 and hepatitis A 86 vaccines in patients receiving methotrexate (15-20 mg per week), 85,86 azathioprine, or cyclosporine. 85,87,88 Satisfactory immune responses to influenza vaccine and nonviral vaccine (PPSV23, tetanus toxoid) in JAK inhibitoretreated patients with rheumatoid arthritis 89 and inflammatory bowel disease have been observed when vaccines were administered either before the initiation of therapy [90][91][92][93] or after temporary withdrawal of JAK inhibitors 2 to 3 weeks before vaccination, 89,94,95 which is consistent with most consensus guideline recommendations. 3,70,71 Overall, vaccine efficacy may be reduced in patients receiving systemic immune-targeting therapies because of the impaired immune response in these patients; however, temporary withdrawal and/or additional vaccinations may be considered to achieve adequate protection.…”

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“…Several patients with COVID‐19, treated with hydroxychloroquine/chloroquine, had lower IgG antibody responses than expected on recovery 18 Satisfactory humoral response to PCV13 at 4 weeks occurred in ~two‐thirds of patients with rheumatoid arthritis receiving long‐term treatment with upadacitinib and background methotrexate, which was similar to placebo 19 Limited studies on newer generation biologic agents used in chronic plaque psoriasis and atopic dermatitis suggest little to no interference to seasonal influenza, pneumococcal or tetanus vaccine.…”

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“…PCV-13 vaccination was successful in 68% of patients with rheumatoid arthritis treated with the JAK1/2 inhibitor baricitinib, whereas only 43% achieved an at least fourfold increase in antitetanus IgG concentrations. However, most patients in this study were also taking methotrexate (89%) and/or corticosteroids (30%) [ 36 ]. Similar results were found for the JAK1 inhibitor upadacitinib, with a satisfactory humoral response (at least twofold increase in antibody levels compared with baseline) to PCV-13 at 12 weeks in 65% and 55% of patients for 15 mg and 30 mg upadacitinib, respectively [ 37 ].…”