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

Similar levels of disease activity and remission rates in patients with psoriatic arthritis and rheumatoid arthritis : results from the Finnish quality register

Objectives: To compare the current disease activity and remission rates, and their regional variation in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in Finland. Methods: Data of patients’ most recent visit in 1/2020–9/2021 were extracted from the Finnish Rheumatology Quality Register. Measures for disease activity and remission included joint counts, DAS28, cDAPSA, CDAI, the Boolean definition, and physician assessment. Regression analyses were applied, adjusted for age and sex. Results: Data of 3598 patients with PsA (51% female, mean age 54 years) and 13,913 patients with RA (72% female, 74% ACPA-positive, mean age 62 years) were included. The median (IQR) DAS28 was 1.9 (1.4, 2.6) in PsA and 2.0 (1.6, 2.7) in RA (p = 0.94); for cDAPSA, the median (IQR) values were 7.7 (3.1, 14) in PsA and 7.7 (3.3, 14) in RA (p < 0.001). In all regions in both diseases, the median DAS28 was ≤ 2.6 and the median cDAPSA < 13. Remission rates included DAS28 < 2.6 in 73% in PsA and 69% in RA (p = 0.17) and Boolean remission in 17% in PsA and 15% in RA (p < 0.001). By other definitions of remission, the rates ranged between 30% and 46%. Methotrexate was currently used by 49% in PsA and 57% in RA (p < 0.001). Self-administered bDMARDs were currently used by 37% in PsA and 21% in RA (p < 0.001). Conclusion: The overall disease activity was low and similar in patients with PsA and RA across the country. Remission rates varied between 15 and 73%, depending on the definition but were similar in PsA and RA. Key Points • The disease activity and clinical picture was similar between patients with PsA and RA, in a cross-sectional setting in 1.2020–9.2021. • A significant majority of patients with PsA had low disease activity or were in remission according to cDAPSA. Majority of patients with RA were in remission according to DAS28. • Patients with PsA and RA used methotrexate similarly. The utilization of bDMARDs was more prevalent in patients with PsA.Peer reviewe

Intense symptoms of pain are associated with poor sleep, fibromyalgia, depression and sleep apnea in patients with rheumatoid arthritis and psoriatic arthritis : A register-based study

Objectives: To study whether poor sleep and comorbidities are associated with high symptom levels of patient-reported outcomes (PROs) pain, patient global assessment and fatigue in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in a nation-wide cross-sectional setting. Methods: Clinical data were extracted from The Finnish Rheumatology Quality Register between 1.2021 and 9.2022. Self-reported sleep was categorized as “good” (little/no difficulties) or “poor” (great difficulties/can't) sleep. Data concerning comorbidities were collected from national registers. Descriptive statistics were used. Regression analyses were applied to analyze independent associations of sleep status, comorbidities and disease activity with pain in RA and PsA, adjusting for age and sex. Results: Among 13,512 patients with RA, 6052 [mean (SD) age 62 (13), 71% female] had sleep status reported; in PsA 1861/3636 [age 55 (13), 48% female]. In RA, 5072 (84%) reported good and 980 (16%) poor sleep; the corresponding numbers in PsA were 1460 (78%) and 401 (22%). Median values for objective disease activity were low and similar in patients with poor sleep and good sleep in both diseases. Among patients with no swollen joints, the median values for PROs were approximately three times higher for patients with poor sleep vs. good sleep in both diagnoses (P < 0.001). In regression analyses, “poor” sleep was independently associated with higher symptoms in pain [B (95%CI) 20 (18,22) in RA and 23 (19, 26) in PsA], followed by comorbid fibromyalgia, as well as depression in RA and sleep apnea in PsA. Conclusion: “Poor” sleep quality and comorbidities are independently associated with pain. Patient's sleep status is important to know especially in patients with severe symptoms without objective disease activity.Peer reviewe

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

Incidence of juvenile idiopathic arthritis in Finland, 2000-2020

Objective: Previous epidemiological data of JIA in Finland are from the turn of the millennium. We aimed to determine the recent annual incidence of JIA in several consecutive years in Finland and to explore the differences in incidence between sexes, age groups and regions. Methods: We analysed all children <16 years of age who met the ILAR classification criteria for JIA. Cases from 2000-2020 were identified from two national registers: the Care Register for Health Care of the Finnish Institute for Health and Welfare and the Reimbursement Register containing medication data from the Social Insurance Institution of Finland; cases from 2016-2020 were identified from the Finnish Rheumatology Quality Register. Results: The incidence of JIA was 31.7 per 100 000 (95% CI 30.2, 33.1), according to the Care Register in 2000-2020 and peaked in 2010-2014. No considerable differences in incidence rates were observed among registers. In all age groups, incidence in girls was predominant compared with boys. The incidence in girls peaked at the ages of 2 years and 14-15 years. Decreasing incidence was observed among boys 0-3 years old during the entire study period, whereas increasing incidence was observed among teenage girls and boys 4-7 years old in 2000-2013. Conclusion: The incidence of JIA is not only very high with respect to that in other parts of the world but also higher than previously reported in Finland. The incidence varied by region and year but was not higher at the end than the beginning of the study period.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