The Role of Microbiome on Biological Therapy Efficacy in axSpA and RA

• Conditions: Arthritis, Rheumatoid; Axial Spondyloarthritis
• Interventions: Biological: biological disease-modifying antirheumatic drugs (bDMARDs)

• Registration Number: NCT04973787
• Lead Sponsor: Universidade Nova de Lisboa

Brief Summary

Spondyloarthritis (SpA) and Rheumatoid arthritis (RA) are among the most common chronic inflammatory rheumatic diseases. Introduction of Tumor Necrosis Factor alpha inhibitors (TNFi) to the therapeutic strategy improved acute inflammation and pain, but a significant percentage of patients develop severe adverse events or are still non responders or incomplete responders to these expensive treatments. There is an urgent need to identify new predictors of biological therapy response. It has been described the role of microbiota in some rheumatic diseases, however, clinical trials are scarce. We hypothesized that microbiota or their metabolites may play a role in therapeutic response to TNFi.

Detailed Description

Thus, this project aimed to evaluate the influence of oral and gut microbiota in the therapeutic response to biologic therapies, in 60 patients.

It is expected to enrolled 30 SpA and 30 RA patients and 30 controls, crossed by gender, age and diet profile. Oral and fecal microbiota will be characterized before TNFi therapeutic. Patients will have an additional microbiota and metabolic profile characterization 14 weeks late after.

This will allow to identify specific profiles of oral and gut microbiome and/or specific biochemical patterns in these patients. At week 14 it will be possible to identify changes induced by TNFi. In addition, it will be possible to identify microbiota pattern associated clinical therapeutic TNFi response vs non-response.

This will allow to predict isolate microbe or microbes patterns at baseline associated to clinical response obtained at week 14. These results may additionally contribute to clinical decision and a better evidenced-based treatment.

Study Timeline

• Study Start: 2020-08-01
• Study First Submitted: 2021-06-22
• Status Verified: 2021-07
• Study First Submitted QC: 2021-07-12
• Last Update Submitted: 2021-07-12
• Study First Posted: 2021-07-22
• Last Update Posted: 2021-07-22
• Primary Completion: 2022-01-31
• Study Completion: 2022-01-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Diagnosis of axSpA (according to ASAS classification criteria) or RA (according to 2010 ACR/EULAR classification criteria);
2. Indication for bDMARD therapy, according to the Portuguese recommendations for the use of biological therapies in patients with axSpA and RA;
3. Oral corticosteroids (equivalent to prednisolone ≤ 10mg/day) and/or nonsteroidal anti-inflammatory drugs allowed at stable dose ≥4 weeks before baseline;
4. Conventional DMARDs allowed at stable dose ≥12 weeks before baseline;
5. Ability to provide informed consent.

Exclusion Criteria

1. History of rheumatic disorder other than axSpA or RA;
2. History of Inflammatory Bowel Disease;
3. Previous treatment with bDMARD;
4. Current pregnancy or breastfeeding;
5. Malignancy (except for completely treated squamous or basal cell carcinoma);
6. Any uncontrolled medical condition (e.g., uncontrolled diabetes mellitus, unstable ischemic heart disease);
7. History of any documented gastrointestinal disease or tract surgery leaving permanent residua (e.g., gastrectomy, bariatric surgery, or colectomy);
8. Intraarticular injections of extra-axial joints and tendons within 28 days before or at baseline;
9. Recent (<3 months prior) use of any antibiotic therapy, current extreme diet (e.g., parenteral nutrition or macrobiotic diet), current consumption of probiotics.

Control group will be healthy participants, and the same inclusion and exclusion criteria will be applied except for rheumatic disease diagnosis.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
RA	biological disease-modifying antirheumatic drugs (bDMARDs)	Patients with clinical diagnosis of Rheumatoid arthritis according to 2010 ACR/EULAR classification criteria, with indication for bDMARD (Portuguese Rheumatology Society Guidelines)
axSpA	biological disease-modifying antirheumatic drugs (bDMARDs)	Patients with clinical diagnosis of axialSpondyloarthritis according to ASAS criteria, with indication for bDMARD (Portuguese Rheumatology Society Guidelines)

Primary Outcome Measures

Name	Time	Method
Oral and gut microbiota characterization in axSpA and RA patients at baseline	Before bDMARD
Oral and gut microbiota characterization in axSpA and RA patients at week 14	14 weeks after start bDMARD
Disease activity measured by ASAS20 in axSpA and ACR20 in RA	14 weeks after start bDMARD

Secondary Outcome Measures

Name	Time	Method
Changes in Erythrocyte Sedimentation Rate (ESR, measured in mm/h)	Before bDMARD and 14-week after start bDMARD
Disease activity characterization using Ankylosing Spondylitis Disease Activity Score - C-Reactive Protein (ASDAS-CRP) in axSpA	Before bDMARD and 14-week after start bDMARD	\< 1.3 Inactive disease; \> 3.5 Very high disease activity
Quality of life evaluation with Short form 36 (SF36) at baseline and week 14	Before bDMARD and 14-week after start bDMARD	Score from 0 (worse outcome) to 100 (better outcome)
Quality of life evaluation with Ankylosing Spondylitis Quality of Life (ASQOL) at baseline and week 14	Before bDMARD and 14-week after start bDMARD	Range from 0 -18 - High scores indicate worse quality of life
Disease activity characterization using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in axSpA	Before bDMARD and 14-week after start bDMARD	Scale from 0 (worse outcome) to 10 (better outcome)
Quality of life evaluation with Health Assessment Questionnaire (HAQ) at baseline and week 14	Before bDMARD and 14-week after start bDMARD	Scores of 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 moderate to severe disability, and 2 to 3 severe to very severe disability
Quality of life evaluation regarding depression and anxiety using Hospital Anxiety and Depression Scale (HADS) at baseline and week 14	Before bDMARD and 14-week after start bDMARD	Scores of less than 7 indicate non-cases; 8-10 Mild; 11-14 Moderate;15-21 Severe
Changes in High-sensitivity C-reactive protein (hsCRP, measured in mg/dL)	Before bDMARD and 14-week after start bDMARD
Disease activity characterization using Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP) for RA	Before bDMARD and 14-week after start bDMARD	Score greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission
Fatigue evaluation at baseline and week 14	Before bDMARD and 14-week after start bDMARD	Visual analogic scale (0-10)

Trial Locations

Locations (10)

Centro Hospitalar Baixo Vouga - Hospital Infante D. Pedro; 🇵🇹 Aveiro, Portugal

Hospital Sousa Martins - Unidade de Saúde Local da Guarda; 🇵🇹 Guarda, Portugal

Hospital de Braga, E.P.E.; 🇵🇹 Braga, Portugal

Instituto Português de Reumatologia; 🇵🇹 Lisboa, Portugal

Centro Hospitalar de Vila Nova da Gaia/Espinho; 🇵🇹 Vila Nova De Gaia, Portugal

Centro Hospitalar Universitário de Lisboa Norte - Hospital Santa Maria; 🇵🇹 Lisboa, Portugal

Centro Hospitalar Lisboa Ocidental - Hospital Egas Moniz; 🇵🇹 Lisboa, Portugal

Centro Hospitalar de Médio Tejo - Hospital Rainha Santa Isabel - Torres Novas; 🇵🇹 Torres Novas, Portugal

Centro Hospitalar Universitário São João; 🇵🇹 Oporto, Portugal

Unidade Local de Saúde do Alto Minho, Hospital Conde de Bertiandos; 🇵🇹 Ponte de Lima, Portugal