Rapid Anti-Inflammatory Effects of Gonadotropin-Releasing Hormone Antagonism in Rheumatoid Arthritis Patients with High Gonadotropin Levels in the AGRA Trial.

Kåss A, Hollan I, Fagerland MW, Gulseth HC, Torjesen PA, Førre ØT

PloS one13 Oct 2015Cited by 16 (Europe PMC)

PMID26460564PMCIDPMC4603957DOI10.1371/journal.pone.0139439PepBankPUB-26460564

Summary

ObjectivesGonadotropin-releasing hormone (GnRH) and pituitary gonadotropins, which appear to be proinflammatory, undergo profound secretory changes during events associated with rheumatoid arthritis (RA) onset, flares, or improvement e.g. menopausal transition, postpartum, or pregnancy. Potential anti-inflammatory effects of GnRH-antagonists may be most pronounced in patients with high GnRH and gonadotropin levels. Therefore, we investigated the efficacy and safety of a GnRH-antagonist, cetrorelix, in RA patients with high gonadotropin levels.MethodsWe report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99). Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15. Only predefined primary and secondary endpoints were analyzed.ResultsThe primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP), improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0∙010). By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism 'Good-responses' (19% vs. 0%, P = 0.026). Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15. Adverse event rates were similar between groups.ConclusionsGnRH-antagonism produced rapid anti-inflammatory effects in RA patients with high gonadotropin levels. GnRH should be investigated further in RA.Trial registrationClinicalTrials.gov NCT00667758.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. 9 results from people.

01HumanRandomized controlled trialEfficacy outcome
In post hoc analyses of RA patients with high gonadotropins, cetrorelix improved DAS28-CRP versus placebo by day 5 (-1.0 versus -0.4, P = 0∙010).
In plain wordsIn RA patients with high gonadotropins, cetrorelix improved disease activity more than placebo by day 5.
Peptide
Cetrorelix
Outcome
DecreaseDAS28-CRP change by day 5
Study
n = 53
Comparator
Placebo
Analysis
Primary
Outcome group
Bone and joint · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Measurements
DAS28-CRP change
−1 points
cetrorelix
DAS28-CRP change
−0.4 points
placebo
Source sentences
Summary
The primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP), improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0∙010).
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056401
02HumanRandomized controlled trialEfficacy outcome
In post hoc analyses of RA patients with high gonadotropins, cetrorelix increased ACR20 responses versus placebo by day 5 (44% versus 19%, P = 0.049).
In plain wordsIn RA patients with high gonadotropins, cetrorelix increased ACR20 responses compared with placebo.
Peptide
Cetrorelix
Outcome
IncreaseACR20 response by day 5
Study
n = 53
Comparator
Placebo
Outcome group
Bone and joint · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Measurements
ACR20 response
44%
cetrorelix
ACR20 response
19%
placebo
Source sentences
Summary
By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism 'Good-responses' (19% vs. 0%, P = 0.026).
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056402
03HumanRandomized controlled trialEfficacy outcome
In post hoc analyses of RA patients with high gonadotropins, cetrorelix increased DAS28-CRP≤3.2 attainment versus placebo by day 5 (24% versus 0%, P = 0.012).
In plain wordsIn RA patients with high gonadotropins, more patients on cetrorelix reached a DAS28-CRP of 3.2 or lower than on placebo by day 5.
Peptide
Cetrorelix
Outcome
IncreaseDAS28-CRP≤3.2 by day 5
Study
n = 53
Comparator
Placebo
Outcome group
Bone and joint · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Measurements
DAS28-CRP≤3.2
24%
cetrorelix
DAS28-CRP≤3.2
0%
placebo
Source sentences
Summary
By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism 'Good-responses' (19% vs. 0%, P = 0.026).
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056403
04HumanRandomized controlled trialEfficacy outcome
In post hoc analyses of RA patients with high gonadotropins, cetrorelix increased EULAR Good-responses versus placebo by day 5 (19% versus 0%, P = 0.026).
In plain wordsIn RA patients with high gonadotropins, cetrorelix increased EULAR Good-responses compared with placebo.
Peptide
Cetrorelix
Outcome
IncreaseEULAR Good-response by day 5
Study
n = 53
Comparator
Placebo
Outcome group
Bone and joint · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Measurements
EULAR Good-response
19%
cetrorelix
EULAR Good-response
0%
placebo
Source sentences
Summary
By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism 'Good-responses' (19% vs. 0%, P = 0.026).
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056404
05HumanRandomized controlled trialEfficacy outcome
In post hoc analyses of RA patients with high gonadotropins, cetrorelix decreased TNF-α versus placebo by day 15 (P = 0.045).
In plain wordsIn RA patients with high gonadotropins, cetrorelix reduced TNF-α compared with placebo.
Peptide
Cetrorelix
Outcome
DecreaseTNF-α by day 15
Study
n = 53
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Source sentences
Summary
Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15.
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056405
06HumanRandomized controlled trialEfficacy outcome
In post hoc analyses of RA patients with high gonadotropins, cetrorelix decreased interleukin-1β versus placebo by day 15 (P = 0.034).
In plain wordsIn RA patients with high gonadotropins, cetrorelix reduced interleukin-1β compared with placebo.
Peptide
Cetrorelix
Outcome
DecreaseInterleukin-1β by day 15
Study
n = 53
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Source sentences
Summary
Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15.
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056406
07HumanRandomized controlled trialEfficacy outcome
In post hoc analyses of RA patients with high gonadotropins, cetrorelix decreased interleukin-10 versus placebo by day 15 (P = 0.020).
In plain wordsIn RA patients with high gonadotropins, cetrorelix reduced interleukin-10 compared with placebo.
Peptide
Cetrorelix
Outcome
DecreaseInterleukin-10 by day 15
Study
n = 53
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Source sentences
Summary
Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15.
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056407
08HumanRandomized controlled trialEfficacy outcome
In post hoc analyses of RA patients with high gonadotropins, cetrorelix decreased CRP versus placebo by day 15 (P = 0.042).
In plain wordsIn RA patients with high gonadotropins, cetrorelix reduced CRP compared with placebo.
Peptide
Cetrorelix
Outcome
DecreaseCRP by day 15
Study
n = 53
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Source sentences
Summary
Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15.
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056408
09HumanRandomized controlled trialSafety outcome
In post hoc analyses of RA patients with high gonadotropins, adverse event rates were similar with cetrorelix and placebo.
In plain wordsIn RA patients with high gonadotropins, adverse event rates were similar with cetrorelix and placebo.
Peptide
Cetrorelix
Outcome
No significant changeAdverse event rate
Study
n = 53
Comparator
Placebo
Outcome group
Adverse events · Immune and inflammation
Studied dose
5mg days1-2; 3mg days 3-5 · subcutaneousAs given in this study (human).
Source sentences
Summary
Adverse event rates were similar between groups.
3 context sentences(design, population, supporting numbers)
Summary · context
We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99).
Summary · context
Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15.
Summary · context
Only predefined primary and secondary endpoints were analyzed.
Show in the study text Report a problemFND-2646056409

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT00667758

Gonadotropin-Releasing Hormone (GnRH)-Antagonist Therapy in Rheumatoid Arthritis

Betanien Hospitaln = 104May 2008 to Oct 2011

Rheumatoid Arthritis

Trial page ClinicalTrials.govUpdated 6 Aug 2012

Version history

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Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:35 UTC
First added · source update from Europe PMC

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