See the published version of this article at Arthritis Research & Therapy.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
The Multi-biomarker Disease Activity test for assessing response to treatment strategies using methotrexate with or without prednisone in the CAMERA-II Trial
Mary Safy-Khan
Universitair Medisch Centrum Utrecht
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0962-9377
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Arthritis Research & Therapy.
Objectives The CAMERA-II trial compared two tight-control, treat-to-target strategies, initiating methotrexate with prednisone (MTX+pred) or MTX with placebo (MTX+plac), in early RA-patients. The multi-biomarker disease activity (MBDA) blood test objectively measures RA disease activity with a score of 1−100. In CAMERA-II, response profiles of the MBDA score, its individual biomarkers and DAS28 were assessed.
Methods We evaluated 92 patients from CAMERA-II of whom clinical data and serum for MBDA testing at baseline and ≥1 timepoint from months 1, 2, 3, 4, 5, 6, 9 or 12 were available. Changes (∆) from baseline for DAS28 and MBDA score and comparisons of ∆DAS28 and ∆MBDA score over time within the MTX+pred versus the MTX+plac strategy, were tested for significance with t-tests. Changes in biomarker concentration from baseline to months 1−5 were tested with Wilcoxon signed rank test and tested for difference between treatment arms by Mann-Whitney U test.
Results MBDA and DAS28 showed similar response profiles, with gradual improvement over the first 6 months in the MTX+plac group, and in the MTX+pred group faster improvement during month 1, followed by gradual improvement. The 12 MBDA biomarkers could be grouped into 4 categories of response profiles, with significant responses for 4 biomarkers during the MTX+plac strategy and 9 biomarkers during the MTX+pred strategy.
Conclusions MBDA tracked treatment response in CAMERA-II similarly to DAS28. More individual MBDA biomarkers tracked treatment response of MTX+pred than of MTX+plac. Four response profiles could be observed.
TRIAL REGISTRATION
CAMERA-II International Standard Randomised Controlled Trial Number: ISRCTN 70365169. Registered 29 March 2006, retrospectively registered.
Keywords
Rheumatoid arthritis, multi-biomarker disease activity score, DAS28, biomarkers, CAMERA-II
Figure 1
Figure 2
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 15 Aug, 2020
Published
On 09 Sep, 2020
No community comments so far
Review #1 received
Received 10 Aug, 2020
Editorial decision: Accept
On 10 Aug, 2020
Review #2 received
Received 09 Aug, 2020
Reviewer #1 agreed
On 06 Aug, 2020
Reviewer #2 agreed
On 06 Aug, 2020
Editor assigned
On 05 Aug, 2020
Reviewers invited
Invitations sent on 05 Aug, 2020
Submission checks complete
On 04 Aug, 2020
Editor invited
On 04 Aug, 2020
No comments provided
Review #1 received
Received 08 Jun, 2020
Editorial decision: Major revision
On 08 Jun, 2020
Review #2 received
Received 07 Jun, 2020
Reviewer #2 agreed
On 24 May, 2020
Reviewer #1 agreed
On 21 May, 2020
Reviewers invited
Invitations sent on 27 Mar, 2020
Editor assigned
On 31 Jan, 2020
First submitted
On 30 Jan, 2020
Submission checks complete
On 30 Jan, 2020
Editor invited
On 30 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This preprint is under consideration at Arthritis Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
The Multi-biomarker Disease Activity test for assessing response to treatment strategies using methotrexate with or without prednisone in the CAMERA-II Trial
Mary Safy-Khan
Universitair Medisch Centrum Utrecht
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0962-9377
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 15 Aug, 2020
Published
On 09 Sep, 2020
No community comments so far
Review #1 received
Received 10 Aug, 2020
Editorial decision: Accept
On 10 Aug, 2020
Review #2 received
Received 09 Aug, 2020
Reviewer #1 agreed
On 06 Aug, 2020
Reviewer #2 agreed
On 06 Aug, 2020
Editor assigned
On 05 Aug, 2020
Reviewers invited
Invitations sent on 05 Aug, 2020
Submission checks complete
On 04 Aug, 2020
Editor invited
On 04 Aug, 2020
No comments provided
Review #1 received
Received 08 Jun, 2020
Editorial decision: Major revision
On 08 Jun, 2020
Review #2 received
Received 07 Jun, 2020
Reviewer #2 agreed
On 24 May, 2020
Reviewer #1 agreed
On 21 May, 2020
Reviewers invited
Invitations sent on 27 Mar, 2020
Editor assigned
On 31 Jan, 2020
First submitted
On 30 Jan, 2020
Submission checks complete
On 30 Jan, 2020
Editor invited
On 30 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Arthritis Research & Therapy.
Objectives The CAMERA-II trial compared two tight-control, treat-to-target strategies, initiating methotrexate with prednisone (MTX+pred) or MTX with placebo (MTX+plac), in early RA-patients. The multi-biomarker disease activity (MBDA) blood test objectively measures RA disease activity with a score of 1−100. In CAMERA-II, response profiles of the MBDA score, its individual biomarkers and DAS28 were assessed.
Methods We evaluated 92 patients from CAMERA-II of whom clinical data and serum for MBDA testing at baseline and ≥1 timepoint from months 1, 2, 3, 4, 5, 6, 9 or 12 were available. Changes (∆) from baseline for DAS28 and MBDA score and comparisons of ∆DAS28 and ∆MBDA score over time within the MTX+pred versus the MTX+plac strategy, were tested for significance with t-tests. Changes in biomarker concentration from baseline to months 1−5 were tested with Wilcoxon signed rank test and tested for difference between treatment arms by Mann-Whitney U test.
Results MBDA and DAS28 showed similar response profiles, with gradual improvement over the first 6 months in the MTX+plac group, and in the MTX+pred group faster improvement during month 1, followed by gradual improvement. The 12 MBDA biomarkers could be grouped into 4 categories of response profiles, with significant responses for 4 biomarkers during the MTX+plac strategy and 9 biomarkers during the MTX+pred strategy.
Conclusions MBDA tracked treatment response in CAMERA-II similarly to DAS28. More individual MBDA biomarkers tracked treatment response of MTX+pred than of MTX+plac. Four response profiles could be observed.
TRIAL REGISTRATION
CAMERA-II International Standard Randomised Controlled Trial Number: ISRCTN 70365169. Registered 29 March 2006, retrospectively registered.
Figure 1
Figure 2