CoChat
Sign Up
Cited by 178

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors

Fleischmann, Roy, van Adelsberg, Janet, Lin, Yong, Castelar‐Pinheiro, Geraldo da Rocha, Brzezicki, Jan, Hrycaj, Pawel, Graham, Neil M. H., van Hoogstraten, Hubert, Bauer, Deborah, Burmester, Gerd R.·2017·Arthritis & Rheumatology
DOI 10.1002/art.39944PMC PMC6207906
Open this paper in CoChat — free account

Abstract

Objective: To evaluate the efficacy and safety of sarilumab plus conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) in patients with active moderate‐to‐severe rheumatoid arthritis (RA) who had an inadequate response or intolerance to anti–tumor necrosis factor (anti‐TNF) therapy. Methods: Patients were randomly allocated to receive sarilumab 150 mg, sarilumab 200 mg, or placebo every 2 weeks for 24 weeks with background conventional synthetic DMARDs. The co‐primary end points were the proportion of patients achieving a response according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 24, and change from baseline in the Health Assessment Questionnaire disability index (HAQ DI) at week 12. Each sarilumab dose was evaluated against placebo; differences between the 2 sarilumab doses were not assessed. Results: The baseline characteristics of the treatment groups were similar. The ACR20 response rate at week 24 was significantly higher with sarilumab 150 mg and sarilumab 200 mg every 2 weeks compared with placebo (55.8%, 60.9%, and 33.7%, respectively; P < 0.0001). The mean change from baseline in the HAQ DI score at week 12 was significantly greater for sarilumab (least squares mean change: for 150 mg, −0.46 [ P = 0.0007]; for 200 mg, −0.47 [ P = 0.0004]) versus placebo (−0.26). Infections were the most frequently reported treatment‐emergent adverse events. Serious infections occurred in 1.1%, 0.6%, and 1.1% of patients receiving placebo, sarilumab 150 mg, and sarilumab 200 mg, respectively. Laboratory abnormalities included decreased absolute neutrophil count and increased transaminase levels in both sarilumab groups compared with placebo. In this study, reductions in the absolute neutrophil count were not associated with an increased incidence of infections or serious infections. Conclusion: Sarilumab 150 mg and sarilumab 200 mg every 2 weeks plus conventional synthetic DMARDs improved the signs and symptoms of RA and physical function in patients with an inadequate response or intolerance to anti‐TNF agents. Safety data were consistent with interleukin‐6 receptor blockade and the known safety profile of sarilumab.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/art.39944

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Patient disposition. a = Screen failures mainly resulted from failure to meet the inclusion criterion for disease severity (53%), for not having a high‐sensitivity C‐reactive protein level of ≥8 mg/liter, or because of tuberculosis (21%). b = A total of 5 patients (1 in the placebo group and 4 in the sarilumab 150 mg group) discontinued from the study because their laboratory values measured at baseline were abnormal and precluded them from study inclusion before treatment initiation. AE = adverse event; q2w = every 2 weeks.
Figure 1 Patient disposition. a = Screen failures mainly resulted from failure to meet the inclusion criterion for disease severity (53%), for not having a high‐sensitivity C‐reactive protein level of ≥8 mg/liter, or because of tuberculosis (21%). b = A total of 5 patients (1 in the placebo group and 4 in the sarilumab 150 mg group) discontinued from the study because their laboratory values measured at baseline were abnormal and precluded them from study inclusion before treatment initiation. AE = adverse event; q2w = every 2 weeks.CC BY-NC-ND · PubMed Central
Figure 2 Incidence of American College of Rheumatology 20% criteria for improvement (ACR20), ACR50, and ACR70 responses. A, Proportion of patients who had achieved ACR20, ACR50, and ACR70 responses at week 24. Values inside the bars are the response rates. B, Proportion of patients who had achieved ACR20, ACR50, and ACR70 responses over time. * = P < 0.0001 versus placebo plus conventional synthetic disease‐modifying antirheumatic drug(s) (csDMARD[s]); † = P = 0.0002 versus placebo plus csDMARD(s); ‡ = P = 0.0056 versus placebo plus csDMARD(s). q2w = every 2 weeks.
Figure 2 Incidence of American College of Rheumatology 20% criteria for improvement (ACR20), ACR50, and ACR70 responses. A, Proportion of patients who had achieved ACR20, ACR50, and ACR70 responses at week 24. Values inside the bars are the response rates. B, Proportion of patients who had achieved ACR20, ACR50, and ACR70 responses over time. * = P < 0.0001 versus placebo plus conventional synthetic disease‐modifying antirheumatic drug(s) (csDMARD[s]); † = P = 0.0002 versus placebo plus csDMARD(s); ‡ = P = 0.0056 versus placebo plus csDMARD(s). q2w = every 2 weeks.CC BY-NC-ND · PubMed Central
Figure 3 Mean change from baseline in Health Assessment Questionnaire disability index (HAQ DI) scores. A, Least squares mean (LSM) change from baseline in HAQ DI scores at week 12. B, LSM change from baseline in the HAQ DI over time according to treatment group. C, Proportion of patients who had achieved improvement in the HAQ DI of ≥0.22 units at week 24. D, Proportion of patients who had achieved improvement in the HAQ DI of ≥0.30 units at week 24. In C and D, values inside the bars are the response rates. * = P < 0.0001 versus placebo plus csDMARDs; † = P < 0.01 versus placebo plus csDMARDs; ‡ = P < 0.05 versus placebo plus csDMARDs. Dotted vertical line indicates the time point after which rescue was permitted. See Figure 2 for other definitions.
Figure 3 Mean change from baseline in Health Assessment Questionnaire disability index (HAQ DI) scores. A, Least squares mean (LSM) change from baseline in HAQ DI scores at week 12. B, LSM change from baseline in the HAQ DI over time according to treatment group. C, Proportion of patients who had achieved improvement in the HAQ DI of ≥0.22 units at week 24. D, Proportion of patients who had achieved improvement in the HAQ DI of ≥0.30 units at week 24. In C and D, values inside the bars are the response rates. * = P < 0.0001 versus placebo plus csDMARDs; † = P < 0.01 versus placebo plus csDMARDs; ‡ = P < 0.05 versus placebo plus csDMARDs. Dotted vertical line indicates the time point after which rescue was permitted. See Figure 2 for other definitions.CC BY-NC-ND · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 38

  1. 10.1136/annrheumdis-2013-204573 · DOI
  2. 10.1002/art.39480 · DOI
  3. 10.1093/rheumatology/kes115 · DOI
  4. 10.1002/art.22331 · DOI
  5. 10.1038/nrrheum.2015.8 · DOI
  6. 10.1186/ar1917 · DOI
  7. 10.1158/2326-6066.CIR-14-0022 · DOI
  8. 10.1136/ard.59.suppl_1.i21 · DOI
  9. 10.1177/1759720X10378372 · DOI
  10. 10.1093/rheumatology/38.3.202 · DOI
  11. 10.1007/s00296-006-0143-2 · DOI
  12. 10.1097/00124743-199504000-00006 · DOI
  13. 10.1186/ar1916 · DOI
  14. 10.1136/ard.2008.092932 · DOI · Paper page
  15. 10.1136/annrheumdis-2012-202470 · DOI
  16. 10.1002/art.30158 · DOI
  17. 10.1136/annrheumdis-2011-200395 · DOI
  18. 10.1002/art.39093 · DOI · Paper page
  19. 10.1136/annrheumdis-2013-204405 · DOI
  20. 10.1002/art.27584 · DOI
  21. 10.1002/art.1780360601 · DOI
  22. 10.1002/art.1780380602 · DOI
  23. 10.1002/art.1780230202 · DOI
  24. 10.1002/art.1780380107 · DOI
  25. 10.1002/1529-0131(200007)43:7<1478::AID-ANR10>3.0.CO;2-M · DOI
  26. 10.1016/S0140-6736(12)61424-X · DOI
  27. 10.1056/NEJMoa050524 · DOI
  28. 10.1136/annrheumdis-2013-204920 · DOI
  29. 10.1093/rheumatology/keq343 · DOI
  30. 10.1136/annrheumdis-2013-205137 · DOI · Paper page
  31. 10.1136/annrheumdis-2013-204760 · DOI · Paper page
  32. 10.1136/ard.2008.101378 · DOI
  33. 10.1136/ard.2008.105197 · DOI · Paper page
  34. 10.1155/2014/698313 · DOI
  35. 10.1136/ard.2009.122374 · DOI
  36. 10.1016/j.berh.2007.05.007 · DOI
  37. 10.3899/jrheum.120573 · DOI
  38. Boyapati A, 2015, Evaluation of bone and joint proteins for prognostic association with radiographic progression and disease activity in methotrexate inadequate responder rheumatoid arthritis patients in a sarilumab phase 3 study [abstract], Arthritis Rheumatol, 67

Cited by

Sorted by citations

See all 178

Metadata

Authors
Fleischmann, R., van Adelsberg, J., Lin, Y., Castelar‐Pinheiro, G. D. R., Brzezicki, J., Hrycaj, P., Graham, N. M. H., van Hoogstraten, H., Bauer, D., & Burmester, G. R.
Affiliations
  • Metroplex Clinical Research Center and University of Texas Southwestern Medical Center Dallas
  • Regeneron Pharmaceuticals Tarrytown New York
  • Sanofi Bridgewater New Jersey
  • Rio de Janeiro State University Rio de Janeiro Brazil
  • Centrum Kliniczno‐Badawcze Elblag Poland
  • Poznań University of Medical Sciences Poznań Poland
  • Charité University Medicine Free University, and Humboldt University, Berlin Germany
Venue
Arthritis & Rheumatology
Publisher
Wiley
Published
2017-01-28
Volume
69
Issue
2
Pages
277-290
ISSN
  • 2326-5191
  • 2326-5205
DOI
10.1002/art.39944
PMC
PMC6207906
Cited by
178
References
2
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Funders
Sanofi and Regeneron Pharmaceuticals

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review