For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
37
views
58
references
 Top references
cited by
91
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      234
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to evaluate whether concomitant treatment with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib.

          Methods

          HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long‐term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient‐years (with 95% confidence intervals [95% CIs]) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies.

          Results

          Across all studies (6,192 patients; 16,839 patient‐years), HZ was reported in 636 tofacitinib‐treated patients (IR 4.0, 95% CI 3.7–4.4). In most cases (93%), HZ was classified as nonserious, and the majority of patients (94%) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95% CI 2.0–2.9) in Eastern Europe to 8.0 (95% CI 6.6–9.6) in Japan and 8.4 (95% CI 6.4–10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 [95% CI 0.07–2.01]) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 [95% CI 3.72–7.68]). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ.

          Conclusion

          Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs.

          Related collections

          Most cited references58

          • Record: found
          • Abstract: found
          • Article: not found

          Measurement of patient outcome in arthritis.

          R KRAINES, P Spitz, J Fries … (1980)
          A structure for representation of patient outcome is presented, together with a method for outcome measurement and validation of the technique in rheumatoid arthritis. The paradigm represents outcome by five separate dimensions: death, discomfort, disability, drug (therapeutic) toxicity, and dollar cost. Each dimension represents an outcome directly related to patient welfare. Quantitation of these outcome dimensions may be performed at interview or by patient questionnaire. With standardized, validated questions, similar scores are achieved by both methods. The questionnaire technique is preferred since it is inexpensive and does not require interobserver validation. These techniques appear extremely useful for evaluation of long term outcome of patients with rheumatic diseases.
          Article 0 comments Cited 376 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis.

            Roy Fleischmann, Joel Kremer, John M Cush … (2012)
            Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis. In this phase 3, double-blind, placebo-controlled, parallel-group, 6-month study, 611 patients were randomly assigned, in a 4:4:1:1 ratio, to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, placebo for 3 months followed by 5 mg of tofacitinib twice daily, or placebo for 3 months followed by 10 mg of tofacitinib twice daily. The primary end points, assessed at month 3, were the percentage of patients with at least a 20% improvement in the American College of Rheumatology scale (ACR 20), the change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores (which range from 0 to 3, with higher scores indicating greater disability), and the percentage of patients with a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating more disease activity). At month 3, a higher percentage of patients in the tofacitinib groups than in the placebo groups met the criteria for an ACR 20 response (59.8% in the 5-mg tofacitinib group and 65.7% in the 10-mg tofacitinib group vs. 26.7% in the combined placebo groups, P<0.001 for both comparisons). The reductions from baseline in HAQ-DI scores were greater in the 5-mg and 10-mg tofacitinib groups than in the placebo groups (-0.50 and -0.57 points, respectively, vs. -0.19 points; P<0.001). The percentage of patients with a DAS28-4(ESR) of less than 2.6 was not significantly higher with tofacitinib than with placebo (5.6% and 8.7% in the 5-mg and 10-mg tofacitinib groups, respectively, and 4.4% with placebo; P=0.62 and P=0.10 for the two comparisons). Serious infections developed in six patients who were receiving tofacitinib. Common adverse events were headache and upper respiratory tract infection. Tofacitinib treatment was associated with elevations in low-density lipoprotein cholesterol levels and reductions in neutrophil counts. In patients with active rheumatoid arthritis, tofacitinib monotherapy was associated with reductions in signs and symptoms of rheumatoid arthritis and improvement in physical function. (Funded by Pfizer; ORAL Solo ClinicalTrials.gov number, NCT00814307.).
            Article 0 comments Cited 369 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Tofacitinib or adalimumab versus placebo in rheumatoid arthritis.

              Ronald van Vollenhoven, Roy Fleischmann, Stanley Cohen … (2012)
              Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis. In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity). At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P<0.001 for all comparisons). There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group. Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group. Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts. In patients with rheumatoid arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard ClinicalTrials.gov number, NCT00853385.).
              Article 0 comments Cited 361 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Kevin L. Winthrop: Winthrop@ohsu.edu
                Journal
                Journal ID (nlm-ta): Arthritis Rheumatol
                Journal ID (doi): 10.1002/(ISSN)2326-5205
                Journal ID (publisher-id): ART
                Title: Arthritis & Rheumatology (Hoboken, N.j.)
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 2326-5191
                ISSN (Electronic): 2326-5205
                Publication date (Electronic): 06 September 2017
                Publication date (Print): October 2017
                Volume: 69
                Issue: 10 ( doiID: 10.1002/art.v69.10 )
                Pages: 1960-1968
                Affiliations
                [ 1 ] Oregon Health and Science University Portland
                [ 2 ] University of Alabama at Birmingham
                [ 3 ] Ochsner Medical Center Baton Rouge Louisiana
                [ 4 ] University of Occupational and Environmental Health Japan Kitakyushu Japan
                [ 5 ] Keio University School of Medicine Tokyo Japan
                [ 6 ] Pfizer New York New York
                [ 7 ] Pfizer Japan Tokyo Japan
                [ 8 ] Pfizer Inc. Collegeville Pennsylvania
                [ 9 ] Pfizer Groton Connecticut
                Author notes
                [*] [* ]Address correspondence to Kevin L. Winthrop, MD, MPH, Casey Eye Institute, Oregon Health and Science University, 3375 SW Terwilliger Boulevard, Portland, OR 97239. E‐mail: Winthrop@ 123456ohsu.edu .
                Article
                Publisher ID: ART40189
                DOI: 10.1002/art.40189
                PMC ID: 5656820
                PubMed ID: 28845604
                SO-VID: 92b45364-9d9b-4bbb-b1e2-d8139cf753f0
                Copyright © © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
                License:

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Date received : 01 November 2016
                Date accepted : 20 June 2017
                Page count
                Figures: 2, Tables: 2, Pages: 9, Words: 7572
                Funding
                Funded by: Pfizer
                Funded by: Pfizer Inc
                Categories
                Subject: Rheumatoid Arthritis
                Subject: Rheumatoid Arthritis
                Custom metadata
                source-schema-version-number 2.0
                component-id art40189
                cover-date October 2017
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.1 mode:remove_FC converted:26.10.2017

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content234

                See all similar

                Cited by89

                See all cited by

                Most referenced authors825

                See all reference authors