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Measuring inflammation in rheumatoid arthritis with a new clinical and ultrasound index: development and initial validation

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Abstract

With the aim to develop and validate a clinical + ultrasound (US) inflammation score in rheumatoid arthritis (RA) for use in clinical practice, a mixed-method study was conducted. The theoretical development of the index was achieved with qualitative methodology (discussion group and Delphi survey). Subsequently, a cross-sectional study was carried out to analyse issues related to scoring and validation of the new index. RA patients underwent clinical [28 swollen and tender joints count, patient and physician global assessment (PhGA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)], and US assessments [synovitis or tenosynovitis by grey-scale (GS) and power Doppler (PD) of 42 structures]. An index was created based on statistical models and expert interaction. Construct validity was tested by correlation with DAS28, SDAI, CDAI, and PhGA. Reliability was evaluated in a subgroup of patients with the intraclass correlation coefficient (ICC). US assessment, CRP, and swollen joints were the items that passed the prioritization phase (Delphi study). For the cross-sectional study, 281 patients were randomly divided into design (n = 141) and validation samples (n = 140). The combination of US sites chosen (7 bilaterally) detected the maximum proportion of synovitis and PD present. Three scoring methods were tested: semiquantitative (0–3 GS + 0–3 PD), dichotomous (0/1 GS + 0/1 PD), and qualitative (0/1 based on algorithm). All showed strong correlation with activity measures (ρ ≥ 0.60), and reliability (ICC 0.89–0.93). The index with best parameters of validity, feasibility, and reliability was the qualitative. The final index chosen was the sum of swollen joint count, US qualitative score, and CRP. The UltraSound Activity score is a valid and reliable measure of inflammation in RA equal to the sum of 28 SJC, a simplified (0/1) US assessment of 11 structures and CRP. It is necessary further investigation to demonstrate additional value over existing indices.

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Availability of data and materials

The data sets used and analysed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We acknowledge all rheumatologists participants in the study: Andrea Cuervo Aguilera (Hospital Clinic), Anne Riveros (Hospital de Granollers), Basilio Rodríguez Díez (Hospital Vall d´Hebron), Elena Leonor Sirvent Alierta (Parc Sanitari Sant Joan de Déu), Elisabet Montori (Hospital Plató), Jose Miguel Ruiz Martín (Hospital Viladecans), Laura López Vives (Hospital San Rafael), Maria Bonet (Hospital Vilafranca), Melania Martínez Morillo (Hospital Germans Trias i Pujol), Mireia Castillo (Hospital Universitari Mútua Terrassa), Mireia Moreno Martínez-Losa (Hospital Parc Tauli), Patricia Moya (Hospital Sant Pau), Paula Estrada Alarcón (Hospital Moisés Broggi), Sandra Farietta Varela (Hospital Vall d´Hebron), Susana Holgado Pérez (Hospital Germans Trias i Pujol). Also we are thankful to Rafael Curbelo Rodríguez who at the time was working at InMusc and helped with the design of materials and logistics, as well as the help of Esther Martín-Blas (InMusc), who acted as technical secretariat.

Funding

The study was funded by the Societat Catalana de Reumatologia with a grant from Abbvie. The funding body had no role in the design of the study, collection, analysis, and interpretation of data or in writing the manuscript.

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Authors and Affiliations

  1. Servicio de Reumatología, Hospital Universitari Vall d´Hebron, Passeig de la Vall d’Hebron, 119-129, 08035, Barcelona, Spain

    Juan José de Agustín

  2. Hospital Sant Rafael, Barcelona, Spain

    Alba Erra

  3. Hospital de Granollers, Granollers, Spain

    Andrés Ponce

  4. Hospital Plató, Barcelona, Spain

    Carmen Moragues

  5. Hospital Sant Pau, Barcelona, Spain

    Carmen Moragues, Cesar Díaz-Torné & Patricia Moya

  6. Hospital Moisés Broggi, Sant Joan Despí, Spain

    Delia Reina

  7. Hospital Comarcal de l’Alt Penedès, Vilafranca, Spain

    Estefanía Moreno

  8. Hospital Clinic, Barcelona, Spain

    Julio Ramírez & Raimon Sanmartí

  9. Hospital Germans Trias i Pujol, Badalona, Spain

    Lourdes Mateo

  10. Hospital Universitari Mútua Terrassa, Terrassa, Spain

    Manel Pujol Busquets

  11. Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Spain

    Pilar Santo-Panero

  12. Hospital de Viladecans, Viladecans, Spain

    Sergi Ros-Expósito

  13. Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain

    Javier Narváez

  14. Instituto de Salud Musculoesquelética (InMusc), Madrid, Spain

    Mª Jesús García de Yébenes & Loreto Carmona

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  1. Juan José de Agustín
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Contributions

The study was designed by JJdA, LC, and MJGY. MB, SFV, ACA, AR, SHP, DRS, EM, CDT, MPB, BRD, JMRM, PSP, EC, MMML, AED, LLV, JRG, AP, LMS, MMM, PEA, CMP, PM, MC, SRE, EM, and ELSA contributed as panellists for the qualitative part, recruited the patients, and collected the data. Analyses were carried out by MJGY. The manuscript was drafted by JJdA, MJGY, and LC. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Juan José de Agustín.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

The study was approved by the ethics committee of research (ECR) of the Vall d’Hebron hospital (ID-RTF080) as reference and then by all other ECR involved. All patients signed an informed consent prior to their participation.

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de Agustín, J.J., Erra, A., Ponce, A. et al. Measuring inflammation in rheumatoid arthritis with a new clinical and ultrasound index: development and initial validation. Rheumatol Int 39, 2137–2145 (2019). https://doi.org/10.1007/s00296-019-04383-9

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