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Article ; Online: The impact of autoantibodies on the efficacy of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis: meta-analysis of randomized controlled trials.

Takase-Minegishi, Kaoru / Böhringer, Stefan / Nam, Jackie L / Kaneko, Yuko / Behrens, Frank / Saevarsdottir, Saedis / Detert, Jacqueline / Leirisalo-Repo, Marjatta / van der Heijde, Désirée / Landewé, Robert / Ramiro, Sofia / van der Woude, Diane

Rheumatology (Oxford, England)

2024

Abstract: Objective: To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies.: Methods: Previous systematic literature reviews performed by EULAR RA management task forces were searched for ... ...

Abstract	Objective: To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies. Methods: Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF + vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses. Results: Data from 28 eligible RCTs were analyzed, pooling 23 studies in three subgroups: 6 including csDMARD-naïve patients, 14 csDMARD-IR, and 3 TNFi-IR patients. In csDMARD-naïve and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88-1.18) and 1.09 (0.90-1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on 3 trials, the 6-month ACR20 RRR was 2.28 (1.31-3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs. Conclusion: The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used.
Language	English
Publishing date	2024-02-16
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keae113
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Article: Myocardial T1 mapping by cardiac magnetic resonance imaging shows early myocardial changes in treatment-naive patients with active rheumatoid arthritis and positive autoantibodies.

Federico, Johanna A / Syväranta, Suvi A / Tuohinen, Suvi S / Holmström, Miia M / Peltomaa, Ritva L / Koivuniemi, Riitta P / Kestilä, Mari H / Kaasalainen, Touko T / Peltonen, Juha I / Leirisalo-Repo, Marjatta T K / Kivistö, Sari M / Vaara, Satu M

Clinical and experimental rheumatology

2024

Abstract: Objectives: We aimed to study whether myocardial changes are already detectable by cardiac magnetic resonance (CMR) imaging at the time of rheumatoid arthritis (RA) diagnosis.: Methods: This single-centre prospective study included 39 treatment-naive ...

Abstract	Objectives: We aimed to study whether myocardial changes are already detectable by cardiac magnetic resonance (CMR) imaging at the time of rheumatoid arthritis (RA) diagnosis. Methods: This single-centre prospective study included 39 treatment-naive patients with early rheumatoid arthritis (ERA, symptom duration <1 year) without any history of heart disease, and 38 age- and sex-matched healthy volunteers. The disease severity was assessed with clinical evaluation (Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score) and serological testing (rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)). The ERA patients were classified into group A (DAS28-CRP score ≥3.2, positive RF and ACPA; n=17) and group B (not fulfilling the group A criteria). The ERA patients and healthy controls underwent 1.5T CMR. Results: Group A patients had significantly higher myocardial global T1 relaxation times than the healthy controls, 987 [965, 1003] ms vs. 979 [960, 991] ms (median [IQR]; p=0.041). A significant difference in T1 was found in the basal, mid inferior and mid anterolateral segments. In a multivariate analysis, prolonged global T1 relaxation time was independently associated with female sex (95% CI [5.62, 51.31] ms, p=0.016), and group A status (95% CI [4.65, 39.01] ms p=0.014). Conclusions: At the time of diagnosis, ERA patients with a higher disease activity (DAS28-CRP score ≥3.2) and both positive RF and ACPA showed prolonged T1 relaxation times in basal myocardial segments. These segments could be most susceptible to the development of myocardial fibrosis, and a segmental reporting style could be useful when estimating the first signs of myocardial fibrosis.
Language	English
Publishing date	2024-02-06
Publishing country	Italy
Document type	Journal Article
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/8p181d
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Article ; Online: What is the best treatment strategy for early RA?

Leirisalo-Repo, Marjatta

Best practice & research. Clinical rheumatology

2013 Volume 27, Issue 4, Page(s) 523–536

Abstract: Treatment of early rheumatoid arthritis has to be started very early, when the diagnosis is made, preferentially before 6 months of symptoms. Combination therapy with conventional disease-modifying anti-rheumatic drugs (DMARDs) with low-dose, oral ... ...

Abstract	Treatment of early rheumatoid arthritis has to be started very early, when the diagnosis is made, preferentially before 6 months of symptoms. Combination therapy with conventional disease-modifying anti-rheumatic drugs (DMARDs) with low-dose, oral glucocorticoids in the induction phase from the start gives the best results. The patient should be monitored systematically, at start between 1 and 3 months, and the patient should have access to additional visits if a flare or arthritis or adverse event occurs. The treatment should aim to remission (no tender and swollen joints, no signs of inflammatory activity), which can be reached by 60-80% of the patients. Intra-articular glucocorticoid injections as part of the treatment strategy increase the suppression of arthritis and retard joint destruction. Biological drugs are reserved for patients who have consistent active disease and who do not respond to conventional combinations.
MeSH term(s)	Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Drug Therapy, Combination ; Glucocorticoids/therapeutic use ; Humans ; Injections, Intra-Articular
Chemical Substances	Antirheumatic Agents ; Glucocorticoids
Language	English
Publishing date	2013-08
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2052323-3
ISSN	1532-1770 ; 1521-6942
ISSN (online)	1532-1770
ISSN	1521-6942
DOI	10.1016/j.berh.2013.10.002
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Article ; Online: Rheumatoid arthritis patients with predominantly tender joints rarely achieve clinical remission despite being in ultrasound remission.

Hammer, Hilde Berner / Jensen Hansen, Inger Marie / Järvinen, Pentti / Leirisalo-Repo, Marjatta / Ziegelasch, Michael / Agular, Birte / Terslev, Lene

Rheumatology advances in practice

2021 Volume 5, Issue 2, Page(s) rkab030

Abstract: Objectives: Given that subjective variables might reduce remission by composite DAS (CDAS), the main objectives were to explore whether RA patients with mainly tender : Methods: In a Nordic multicentre study, RA patients initiating tocilizumab were ... ...

Abstract	Objectives: Given that subjective variables might reduce remission by composite DAS (CDAS), the main objectives were to explore whether RA patients with mainly tender Methods: In a Nordic multicentre study, RA patients initiating tocilizumab were assessed by PROMs, clinical, laboratory and US assessments (36 joints and 4 tendons) at baseline, 4, 12 and 24 weeks. Remission was defined according to clinical disease activity index (CDAI)/Boolean or no Doppler activity present. Tender-swollen joint differences (TSJDs) were calculated. Statistics exploring changes over time/differences between groups included Wilcoxon, Mann-Whitney, Kruskal-Wallis and Spearman tests. Results: One hundred and ten patients were included [mean (s.d.) age 55.6 (12.1) years, RA duration 8.7 (9.5) years]. All PROMs, clinical, laboratory and US scores decreased during follow-up ( Conclusion: Patients with more tender than swollen joints scored higher on subjective assessments but had less US synovitis. They seldom achieved CDAS remission despite many being in Doppler remission. If patients with predominantly tender joints do not reach CDAS remission, objective assessments of inflammation should be performed. Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov/, NCT02046616.
Language	English
Publishing date	2021-05-14
Publishing country	England
Document type	Journal Article
ISSN	2514-1775
ISSN (online)	2514-1775
DOI	10.1093/rap/rkab030
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Article ; Online: Author Correction: Clonal hematopoiesis in patients with rheumatoid arthritis.

Savola, Paula / Lundgren, Sofie / Keränen, Mikko A I / Almusa, Henrikki / Ellonen, Pekka / Leirisalo-Repo, Marjatta / Kelkka, Tiina / Mustjoki, Satu

Blood cancer journal

2021 Volume 11, Issue 2, Page(s) 36

Language	English
Publishing date	2021-02-17
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-021-00427-1
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Article ; Online: Tofacitinib treatment modulates the levels of several inflammation-related plasma proteins in rheumatoid arthritis and baseline levels of soluble biomarkers associate with the treatment response.

Valli, Atte / Kuuliala, Krista / Virtanen, Anniina / Kuuliala, Antti / Palmroth, Maaria / Peltomaa, Ritva / Vidqvist, Krista-Liisa / Leirisalo-Repo, Marjatta / Silvennoinen, Olli / Isomäki, Pia

Clinical and experimental immunology

2022 Volume 210, Issue 2, Page(s) 141–150

Abstract: The data on the effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analyzed how tofacitinib treatment and thus inhibition of the Janus kinase-signal transducer and activation of ... ...

Abstract	The data on the effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analyzed how tofacitinib treatment and thus inhibition of the Janus kinase-signal transducer and activation of transcription pathway affects the in vivo levels of inflammation-related plasma proteins in RA patients. In this study, 16 patients with active RA [28-joint disease activity score (DAS28) >3.2] despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) started tofacitinib treatment 5 mg twice daily. Levels of 92 inflammation-related plasma proteins were determined by proximity extension assay at baseline and at 3 months. Tofacitinib treatment for 3 months, in csDMARD background, decreased the mean DAS28 from 4.4 to 2.6 (P < 0.001). Marked (>20%) and statistically significant (P < 0.05) changes were found in the levels of 21 proteins, 18 of which decreased and 3 increased. Of these proteins, 17 are directly involved in inflammatory responses or in the cellular response to cytokines. The highest (>50%) decrease was observed for interleukin-6 (IL-6), C-X-C motif chemokine ligand 1, matrix metalloproteinase-1, and AXIN1. Higher baseline levels of IL-6 and lower levels of C-C motif chemokine 11 and Delta and Notch-like epidermal growth factor-related receptors were associated with DAS28 improvement. Our results indicate that tofacitinib downregulates several proinflammatory plasma proteins that may contribute to the clinical efficacy of tofacitinib. In addition, soluble biomarkers may predict the treatment response to tofacitinib.
MeSH term(s)	Humans ; Interleukin-6 ; Pyrroles/therapeutic use ; Pyrroles/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/chemically induced ; Antirheumatic Agents/therapeutic use ; Antirheumatic Agents/adverse effects ; Treatment Outcome ; Biomarkers ; Inflammation/chemically induced ; Blood Proteins ; Chemokines
Chemical Substances	tofacitinib (87LA6FU830) ; Interleukin-6 ; Pyrroles ; Protein Kinase Inhibitors ; Antirheumatic Agents ; Biomarkers ; Blood Proteins ; Chemokines
Language	English
Publishing date	2022-10-18
Publishing country	England
Document type	Journal Article
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxac085
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Article ; Online: Reactive arthritis and other musculoskeletal symptoms associated with acquisition of diarrhoeagenic

Tuompo, Riitta / Lääveri, Tinja / Hannu, Timo / Pakkanen, Sari H / Kirveskari, Juha / Leirisalo-Repo, Marjatta / Kantele, Anu

Annals of the rheumatic diseases

2020 Volume 79, Issue 5, Page(s) 605–611

Abstract: Objectives: Using a prospective research design, we evaluated the association between acquisition of diarrhoeagenic : Methods: A total of 526 study participants were asked to provide pretravel and post-travel stool samples and fill in questionnaires ( ...

Abstract	Objectives: Using a prospective research design, we evaluated the association between acquisition of diarrhoeagenic Methods: A total of 526 study participants were asked to provide pretravel and post-travel stool samples and fill in questionnaires (pretravel, post-travel and 3-week follow-up). A multiplex quantitative PCR assay was deployed to detect five DEC comprising enteroaggregative Results: From among the total of 224 volunteers who returned all questionnaires and stool specimens, 38 (17.0%) reported MSK symptoms. Multivariate analysis revealed that acquisition of DEC was associated with MSK symptoms (OR 3.9; 95% CI 1.2 to 13.3). Of the 151 with only-DEC, four (2.6%) had ReA, two (1.3%) reactive tendinitis and three (2.0%) reactive arthralgia. ReA was mostly mild, and all patients with ReA were negative for human leucocyte antigen B27. Antibiotic treatment of travellers' diarrhoea did not prevent development of MSK symptoms. Conclusion: A total of 17% of volunteers reported post-travel MSK symptoms. DEC acquisition was associated with an increased risk of developing them, yet the ReA incidence remained low and the clinical picture mild. Antibiotic treatment did not protect against development of MSK symptoms.
MeSH term(s)	Academic Medical Centers ; Anti-Bacterial Agents/therapeutic use ; Arthritis, Reactive/epidemiology ; Arthritis, Reactive/etiology ; Arthritis, Reactive/physiopathology ; Cohort Studies ; Diarrhea/complications ; Diarrhea/diagnosis ; Diarrhea/microbiology ; Escherichia coli/pathogenicity ; Escherichia coli Infections/complications ; Escherichia coli Infections/diagnosis ; Female ; Finland ; Humans ; Incidence ; Logistic Models ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction/methods ; Multivariate Analysis ; Musculoskeletal Diseases/epidemiology ; Musculoskeletal Diseases/etiology ; Musculoskeletal Diseases/physiopathology ; Prognosis ; Prospective Studies ; Risk Assessment ; Severity of Illness Index ; Travel-Related Illness
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2020-03-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/annrheumdis-2019-216736
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Article: Early arthritis and infection.

Leirisalo-Repo, Marjatta

Current opinion in rheumatology

2005 Volume 17, Issue 4, Page(s) 433–439

Abstract: Purpose of review: To summarize the recent literature on the association of infection with early arthritis, and to discuss the possible role of such infections with respect to the development of chronic rheumatic complications.: Recent findings: ... ...

Abstract	Purpose of review: To summarize the recent literature on the association of infection with early arthritis, and to discuss the possible role of such infections with respect to the development of chronic rheumatic complications. Recent findings: Viral infections are frequently associated with arthritis. Alphaviruses belong to mosquito-borne viruses, one form of which (Sindbis virus) can in Scandinavia and Karelia cause acute arthritis with typical rash. The role of this infection leading to chronic erosive arthritis needs further prospective studies. Patients infected with HIV can have various forms of arthritis. The role of HIV virus as an arthritogenic agent is still debated. On the basis of population studies, Campylobacter infections seem to be increasing as causative infections in reactive arthritis. There is no role for prolonged antibiotic therapy to shorten the duration of acute reactive arthritis, but the possibility that such a treatment might reduce the development of chronic sequelae needs to be examined in a larger study. The role of preceding infection initiating the process of rheumatoid arthritis is still an option, the association being observed in about 20% of patients studied in the early phase of arthritis. Summary: Viral and microbial infections play a role in acute arthritis. The role of these infections in the development of chronic arthritis needs further prospective controlled studies.
MeSH term(s)	Acute Disease ; Arthritis, Infectious/etiology ; Arthritis, Infectious/physiopathology ; Bacterial Infections/complications ; Bacterial Infections/physiopathology ; Early Diagnosis ; Humans ; Virus Diseases/complications ; Virus Diseases/physiopathology
Language	English
Publishing date	2005-06-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1045317-9
ISSN	1531-6963 ; 1040-8711
ISSN (online)	1531-6963
ISSN	1040-8711
DOI	10.1097/01.bor.0000166388.47604.8b
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Article ; Online: Baseline JAK phosphorylation profile of peripheral blood leukocytes, studied by whole blood phosphospecific flow cytometry, is associated with 1-year treatment response in early rheumatoid arthritis.

Kuuliala, Krista / Kuuliala, Antti / Koivuniemi, Riitta / Kautiainen, Hannu / Repo, Heikki / Leirisalo-Repo, Marjatta

Arthritis research & therapy

2017 Volume 19, Issue 1, Page(s) 75

Abstract: Background: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4: Methods: Thirty-five DMARD-naïve patients with early RA provided blood samples for whole blood flow cytometric ... ...

Abstract	Background: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4 Methods: Thirty-five DMARD-naïve patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4 Results: High JAK3 phosphorylation in CD4 Conclusions: Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA.
MeSH term(s)	Aged ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/metabolism ; Biomarkers/blood ; Female ; Flow Cytometry ; Humans ; Janus Kinases/metabolism ; Lymphocytes/metabolism ; Male ; Middle Aged ; Monocytes/metabolism ; Phosphorylation
Chemical Substances	Antirheumatic Agents ; Biomarkers ; Janus Kinases (EC 2.7.10.2)
Language	English
Publishing date	2017-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-017-1278-0
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Article ; Online: Yersinia enterocolitica biotype 1A: a possible new trigger of reactive arthritis.

Tuompo, Riitta / Hannu, Timo / Huovinen, Elisa / Sihvonen, Leila / Siitonen, Anja / Leirisalo-Repo, Marjatta

Rheumatology international

2017 Volume 37, Issue 11, Page(s) 1863–1869

Abstract: Yersinia enterocolitica (YE) biotype 1A is generally considered non-pathogenic, and the role of it in causing reactive musculoskeletal complications is unclear. We evaluated the capability of YE biotype 1A to induce reactive arthritis (ReA) and other ... ...

Abstract	Yersinia enterocolitica (YE) biotype 1A is generally considered non-pathogenic, and the role of it in causing reactive musculoskeletal complications is unclear. We evaluated the capability of YE biotype 1A to induce reactive arthritis (ReA) and other reactive musculoskeletal symptoms. Analysis of self-reported musculoskeletal symptoms was supplemented with a telephone interview (with a permission to acquire copies of patient files from a local physician or hospital) and/or clinical examination of subjects with recent musculoskeletal symptoms after a positive stool culture for YE. The diagnoses of ReA and reactive tendinitis and enthesitis (ReTe) were defined as "definite" when based on clinical examination and/or on interview by phone and "probable" when based solely on the questionnaire. Of 120 subjects, who reported musculoskeletal symptoms, 100 were included in the final analysis. Among these 100 patients, 68% had YE biotype 1A, 16% YE bio/serotype 4, and 1% biotype 2 infection; the remaining 15% had different YE-like strains or a non-biotypable strain. Of the 21 patients with ReA and of the 14 patients with ReTe, the diagnosis was definite in 9 and 7 patients and probable in 12 and 7 patients, respectively. The clinical picture of ReA caused by YE biotype 1A was similar with other bio/serotypes of YE. The definite ReA due to YE biotype 1A occurred in middle-aged adults (5 men, 4 women) with the most frequently affected joints being the knees and ankles. We suggest that YE biotype 1A should be taken into account as a new trigger of ReA.
Language	English
Publishing date	2017-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8286-7
ISSN	1437-160X ; 0172-8172
ISSN (online)	1437-160X
ISSN	0172-8172
DOI	10.1007/s00296-017-3816-0
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