Cluster analysis identifies unmet healthcare needs among patients with rheumatoid arthritis

Objective: To identify the patterns of healthcare resource utilization and unmet needs of persistent disease activity, pain, and physical disability in rheumatoid arthritis (RA) by cluster analysis. Method: Patients attending the Jyvaskyla Central Hospital rheumatology unit, Finland, were, from 2007, prospectively enrolled in a clinical database. We identified all RA patients in 2010-2014 and combined their individual-level data with well-recorded administrative data on all public healthcare contacts in fiscal year 2014. We ran agglomerative hierarchical clustering (Ward's method), with 28-joint Disease Activity Score with three variables, Health Assessment Questionnaire index, pain (visual analogue scale 0-100), and total annual health service-related direct costs (euro) as clustering variables. Results: Complete-case analysis of 939 patients derived four clusters. Cluster C1 (remission and low costs, 550 patients) comprised relatively young patients with low costs, low disease activity, and minimal disability. C2 (chronic pain, disability, and fatigue, 269 patients) included those with the highest pain and fatigue levels, and disability was fairly common. C3 (inflammation, 97 patients) had rather high mean costs and the highest average disease activity, but lower average levels of pain and less disability than C2, highlighting the impact of effective treatment. C4 (comorbidities and high costs, 23 patients) was characterized by exceptionally high costs incurred by comorbidities. Conclusions: The majority of RA patients had favourable outcomes and low costs. However, a large group of patients was distinguished by chronic pain, disability, and fatigue not unambiguously linked to disease activity. The highest healthcare costs were linked to high disease activity or comorbidities.Peer reviewe

Decreased burden of revision hip replacements despite substantial rise in prevalence : a register-based analysis in Finland

Background and purpose — While the incidence of THR operations has been established, little is known about the prevalence or the ratio of the annual number of revision THRs to the total number of THRs in the general population. By combining data from nationwide registers, we calculated the annual prevalence of THRs and the revision burden caused by THR survivors in Finland. Patients and methods — All primary THRs performed between 1980 and 2020 were identified from the Finnish Arthroplasty Register (FAR). Patient deaths were extracted from the Finnish Digital and Population Data Services Agency and THR revisions and removals from the FAR and the Finnish Hospital Discharge Register. We analyzed annual THR prevalence by dividing the number of THRs by the population aged 40 or older and the revision burden factor (RBF) by dividing the annual number of revisions by the total number of primary and revision THRs in the population. The proportions of bilateral implants and patients with THRs performed more than 10 years earlier (older THRs) were identified. Results — THR prevalence in Finland increased rapidly, reaching 3.6% in 2020. Between 2010 and 2020, the number of THRs increased by 50% and the prevalence of THRs by 38%. In 2020, the proportion of bilateral THRs had risen to 29% and the proportion of patients with older THRs to 36%. The RBF decreased between 1996 and 2020 from 3.1% to 1.3% (age-and sex-adjusted proportion ratio PR 0.42 [95% CI 0.39–0.45]). Interpretation — Despite the decrease in the RBF, the rapidly increasing prevalence of THRs potentially increases the number of revisits and revisions and thus poses a challenge for healthcare in the future.publishedVersionPeer reviewe

Long-Term Increase of Radiographic Damage and Disability in Patients with RA in Relation to Disease Duration in the Era of Biologics. Results from the SCQM Cohort

Objectives: There is little information on the relation between disease duration, disability and radiographic outcome since the introduction of biologics into the therapy of rheumatoid arthritis (RA). No long-term cohort studies have been conducted on this subject so far. To analyse radiographic damage, disability, and disease activity in RA-patients dependent on disease duration in the Swiss national RA cohort (SCQM). Methods: The primary outcome was the association between the radiographic destruction, assessed by Ratingen scores, and disease duration. All patients with at least one clinical visit were analysed with polynomial and multiple negative binomial models. Results: The disease duration in the 8678 patients with available radiographs analysed ranged between less than 1 and more than 65 years (median 8.3). Disease duration and radiographic destruction were significantly associated with an average increase of Ratingen scores by 8.3% per year. Apart from disease duration, positive rheumatoid factor was the strongest predictor for radiographic destruction. While DAS28-scores remained stable in patients with a disease duration of more than 5 years (median DAS28 2.8), HAQ-DI scores increased continuously by 0.018 for each additional year. Conclusion: In this RA cohort, patients show a continuous increase of articular destruction and physical disability in parallel with disease duration. Even when nowadays a satisfactory control of disease activity can be achieved in most patients, RA remains a destructive disease leading to joint destruction and physical disability in many patients

Somatic STAT3 mutations in Felty syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia

Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty syndrome patients who were monitored at the rheumatology outpatient clinic for Felty syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3, which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8(+) T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that ten of the 92 assayed cytokines were elevated both in Felty syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty syndrome as they are in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, a unified reclassification of these two syndromes is warranted.Peer reviewe

Methotrexate safety and efficacy in combination therapies in patients with early rheumatoid arthritis : a post-hoc analysis of a randomized controlled trial (NORD-STAR)

This article is protected by copyright. All rights reserved.OBJECTIVE: To investigate methotrexate safety and influence of dose on efficacy outcomes in combination with three different biological treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA). METHODS: This post-hoc analysis included 812 treatment-naïve early RA patients who were randomized (1:1:1:1) in the NORD-STAR trial (NCT01491815) to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24 weeks of treatment. RESULTS: Compared with ACT, the prevalence of methotrexate-associated side effects was higher when methotrexate was combined with tocilizumab (HR 1.48 [95% CI 1.20 to 1.84]), but not with certolizumab-pegol (HR 0.99 [0.79 to 1.23]) or with abatacept (HR 0.93 [0.75 to 1.16]). With ACT as the reference, methotrexate dose was significantly lower when used in combination with tocilizumab (β -4.65 [95% CI -5.83 to -3.46], p<0.001), with abatacept (β -1.15 [-2.27 to -0.03], p=0.04), and numerically lower in combination with certolizumab-pegol (β -1.07 [-2.21 to 0.07], p=0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations. CONCLUSION: Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/week, and these were more frequent in combination with tocilizumab versus active conventional treatment. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24 weeks. This article is protected by copyright. All rights reserved.Peer reviewe

Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis Is Characterized by a Disease-Specific CD8+T Lymphocyte Signature

Rheumatoid arthritis (RA) is a complex autoimmune disease targeting synovial joints. Traditionally, RA is divided into seropositive (SP) and seronegative (SN) disease forms, the latter consisting of an array of unrelated diseases with joint involvement. Recently, we described a severe form of SN-RA that associates with characteristic joint destruction. Here, we sought biological characteristics to differentiate this rare but aggressive anti-citrullinated peptide antibody-negative destructive RA (CND-RA) from early seropositive (SP-RA) and seronegative rheumatoid arthritis (SN-RA). We also aimed to study cytotoxic CD8+ lymphocytes in autoimmune arthritis. CND-RA, SP-RA and SN-RA were compared to healthy controls to reveal differences in T-cell receptor beta (TCR beta) repertoire, cytokine levels and autoantibody repertoires. Whole-exome sequencing (WES) followed by single-cell RNA-sequencing (sc-RNA-seq) was performed to study somatic mutations in a clonally expanded CD8+ lymphocyte population in an index patient. A unique TCR beta signature was detected in CND-RA patients. In addition, CND-RA patients expressed higher levels of the bone destruction-associated TNFSF14 cytokine. Blood IgG repertoire from CND-RA patients recognized fewer endogenous proteins than SP-RA patients' repertoires. Using WES, we detected a stable mutation profile in the clonally expanded CD8+ T-cell population characterized by cytotoxic gene expression signature discovered by sc-RNA-sequencing. Our results identify CND-RA as an independent RA subset and reveal a CND-RA specific TCR signature in the CD8+ lymphocytes. Improved classification of seronegative RA patients underlines the heterogeneity of RA and also, facilitates development of improved therapeutic options for the treatment resistant patients

Commonalities and differences in set-up and data collection across European spondyloarthritis registries : results from the EuroSpA collaboration

Funding Open access funding provided by Royal Library, Copenhagen University Library The EuroSpA Research Collaboration Network was financially supported by Novartis Pharma AG. Novartis had no influence on the data collection, statistical analyses, manuscript preparation or decision to submit the manuscript.Peer reviewedPublisher PD

Terveydenhuollon kansalliset laaturekisteripilotit loppusuoralla

Pilottiprojektin tulokset laaturekisterien toiminnan organisoimisesta kannustavat ¬jatkamaan työtä moniammatillisesti ja pitkäjänteisesti. Kansallinen koordinaatio on välttämätöntä laatu- ja vaikuttavuustiedon vertailukelpoisuuden ja hyödyntämisen varmistamiseksi