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 Jyväskylä 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 (€) 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.

Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis.

KEY MESSAGES: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

Healthcare costs and outcomes in adult patients with juvenile idiopathic arthritis: a population-based study.

OBJECTIVES: Evidence of the economic burden and long-term outcomes of juvenile idiopathic arthritis (JIA) remains scarce. Our aim was to explore healthcare costs and long-term outcomes in adult patients with JIA. METHOD: We identified all adult patients (≥ 18 years) with JIA who visited Jyväskylä Central Hospital rheumatology unit between May 2007 and March 2016. We considered individual medians of time-dependent clinical variables. These data were linked to administrative data from the area from the fiscal year 2014, which include information on all public healthcare contacts. Healthcare utilization is presented as direct costs in euros (EUR). Factors affecting direct costs were assessed with a generalized linear model. RESULTS: In 218 patients, median 28-joint Disease Activity Score with three variables (DAS28-3) was < 2.6 in 88.6% in those aged < 30 and in 72.9% in those aged ≥ 30 years, and median Health Assessment Questionnaire (HAQ) score was < 0.5 in 85.7% and 45.4%, respectively. In the utilization data (four municipalities, 137 patients), the total annual health services-related direct costs were 432 257 EUR (mean = 3155 EUR/patient/year). Thirty-six patients (26.3%) used biological disease-modifying anti-rheumatic drugs (bDMARDs) in 2014 for a total of 355 months, and the annual cost of bDMARDs was estimated at 355 000 EUR. Those with active disease had mean costs 2.4-fold higher than those with low or no disease activity. A one-point increase in median raw HAQ incurred an average 228 EUR increase in annual costs (p = 0.03). CONCLUSION: Most adult patients with JIA seem to manage well with their arthritis, bearing in mind that there still is room for improvement in long-term outcomes.

Patients with rheumatic diseases share similar patterns of healthcare resource utilization.

Objectives: Healthcare service needs have changed with the use of effective treatment strategies. Using data from the modern era, we aimed to explore and compare health service-related direct costs in juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and axial spondyloarthritis (AxSpA). Methods: We linked a longitudinal, population-based clinical data set from Finland's largest non-university hospital's rheumatology clinic with an administrative database on health service-related direct costs in 2014. We compared all-cause costs and costs of comorbidities between adult patients with JIA, PsA, RA, and AxSpA (including ankylosing spondylitis). We also characterized patients with high healthcare resource utilization. Results: Cost distributions were similar between rheumatic diseases (p = 0.88). In adulthood, patients with JIA displayed a similar economic burden to much older patients with other inflammatory rheumatic diseases. A minority were high utilizers: among 119 patients with JIA, 15% utilized as much as the remaining 85%. For PsA (213 patients), RA (1086), and AxSpA (277), the high-utilization proportion was 10%. Both low and high utilizers showed rather low disease activity, but in high utilizers, the patient-reported outcomes were slightly worse, with the most distinct differences in pain levels. Of health service-related direct costs, index rheumatic diseases comprised only one-third (43.6% in JIA) and the majority were comorbidity costs. Conclusions: Patients with JIA, PsA, RA, and AxSpA share similar patterns of healthcare resource utilization, with substantial comorbidity costs and a minority being high utilizers. Innovations in meeting these patients' needs are warranted.

Psychiatric and cardiovascular comorbidities as causes of long-term work disability among individuals with recent-onset rheumatoid arthritis.

OBJECTIVES: With the ameliorating prognosis of rheumatoid arthritis (RA), the role of comorbidities as causes of work disability (WD) may increase. The aim of this study was to determine the contribution of psychiatric and cardiovascular (CV) comorbidities as the leading causes of long-term WD among patients with recent-onset RA. METHOD: Between 2000 and 2007, all incident, working-age and non-retired RA patients were identified from a Finnish nationwide register. From other registers, we identified the RA patients who were granted a permanent or temporary disability pension by 31 December 2008. The incidences of disability pensions with CV diseases (ICD-10 codes I00-I99) or psychiatric disorders (F20-F69) as the leading causes were assessed and compared with the general population. RESULTS: We identified a cohort of 7831 patients with RA. During follow-up, 1095 patients were granted a disability pension. After adjusting for competing risks, the 9-year cumulative incidence of WD caused by RA, a psychiatric comorbidity, or a CV disease was 11.9, 1.3, and 0.5%, respectively. Compared to the general population, the age- and sex-specific standardized incidence ratio (SIR) of WD due to psychiatric comorbidities was 0.99 [95% confidence interval (CI) 0.80-1.23] and due to CV disease 1.75 (95% CI 1.23-2.51). CONCLUSIONS: In the study cohort with recent-onset RA, the 9-year cumulative incidence of disability pensions caused by psychiatric or CV comorbidities was only 11% or 4%, respectively, of that caused by RA itself. Compared to the general population, the risk of WD due to CV disease was increased.

Sleep problems in fibromyalgia and rheumatoid arthritis compared with the general population.

OBJECTIVE: Our aim was to evaluate how frequently problems of quality and quantity of sleep and depression occur in patients with fibromyalgia (FM), and compare these findings with those occurring in patients with rheumatoid arthritis (RA) and in the general population. MATERIALS AND METHODS: The patients were recruited from rehabilitation courses in the Rheumatism Foundation Hospital, Finland. There were 37 patients with FM and 31 patients with RA participating in the study. For comparison, we used the results from a general population study of 1284 adult subjects. The data had been collected earlier in a longitudinal cohort study for the Finnish Social Insurance Institution. RESULTS: The patients with FM and RA slept fewer hours a day than the population sample. The FM patients reported more insomnia, less contentment with sleep and more lack of deep and restful sleep in comparison to the RA patients and the participants of the population study. The FM patients also reported significantly more depression and pain than the RA patients (p0.01). It was still shown in a logistic regression analysis that insomnia was almost five times more frequent in FM patients than in RA patients, even when depression and pain were adjusted. CONCLUSION: The FM patients reported more insomnia-related symptoms than either RA patients or the population sample. The higher prevalence of insomnia-related symptoms among FM patients was not explained by depression or pain. Both patient groups reported somewhat shorter nocturnal sleep than the general population.

Validation of the Pain Coping Questionnaire in Finnish.

OBJECTIVE: The Pain Coping Questionnaire (PCQ), the first validated pain coping measurement developed specifically for children, has lacked proper validation in Finnish. The original PCQ by Reid et al. (Pain 1998; 76; 83-96) comprises eight-first-order and three higher-order scales. The aim herein was to determine the factor structure and validity of the Finnish PCQ translation in Finnish children. METHODS: Exploratory factor analysis was used for the first-order and higher-order classification of 91 recruited patients aged 8-15. Cronbach's alpha was used for reliability. Relationships between the Children's Depression Inventory, patient-reported pain frequency and pain coping strategies were examined. RESULTS: Analyses were executed with 38 items; one was excluded. A structure of eight-first-order (Internalizing/Catastrophizing [IC], Positive Self-Statements [PSS], Information Seeking [IS], Seeking Social Support [SSS], Cognitive Distraction [CD], Externalizing [EXT], Behavioural Distraction [BD], Problem Solving [PS]) and three higher-order scales (Approach [APP], Emotion-Focused Avoidance [EFA], Distraction [DIS]) proved the most consistent. Four first-order scales (PSS, CD, EXT, BD) emerged as identical to the original solution. Internal consistency reliability coefficients for all individual first- and second-order scales were satisfactory. A higher CDI score was positively related to EFA and negatively to DIS, and pain frequency positively related to APP and EFA. CONCLUSION: The exploratory factor analysis of the PCQ provided a both culturally and statistically satisfactory structure in the Finnish translation. This supports the reliability and validity of the PCQ in future national use and the value of the questionnaire also outside English-speaking countries. SIGNIFICANCE: This study showed both culturally and statistically satisfactory factor structure of PCQ in the Finnish translation. This result supports reliability and validity of the PCQ in the national use in the future. The result shows that the PCQ is a reliable method to be used in different linguistic and cultural surroundings and, thus, encourages using it in various countries. The data consist of two patient groups, adolescents with JIA and musculoskeletal pain. Pain and specifically coping with pain are important aspects of clinical work. A valid pain coping scale may enhance distinguishing vulnerable pain coping style in children and adolescent before pain becomes chronic.

Development rate of mutilans fingers in patients with rheumatic disease.

OBJECTIVE: To describe arthritis mutilans (AM) deformity during the progression of rheumatic disease. METHODS: The development of mutilans-like hand deformities in 2 patients with juvenile chronic arthritis (JCA) and in 2 patients with adult onset rheumatoid arthritis (RA) are presented. The hands of these patients were evaluated at least at two time points during the course of disease using two different scoring methods based on differently summed Larsen grades of the hand joints. RESULTS: Two patients (one with JCA and one with RA) showed AM changes after a disease period of less than 10 years and 2 not until after 30 years. The patients with adult onset disease were young at the onset of joint disease. Early wrist fusions were performed on both patients showing a slow development rate. CONCLUSIONS: The development rate of AM is very variable, even in patients with the same diagnoses. Wrist fusion prevents shortening of the carpus and may decrease the development rate of AM.

Relationship of ankle joint involvement with subtalar destruction in patients with rheumatoid arthritis. A 20-year follow-up study.

AIMS: In the present study we evaluated radiographically involvement of the ankle joint and its relationship to destruction of the subtalar joint in rheumatoid arthritis (RA). METHODS: An inception cohort of 103 patients with seropositive RA was followed over a period of 20 years. Follow-up examinations were conducted after onset, 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15-year and 68 patients the 20-year follow-up. Radiographic evaluation was performed using a lateral weight-bearing ankle radiograph. A simplified grading was applied for the talocrural joint, in which the ankles (patients) were divided into three groups: no changes, minor changes and major changes. In the end-point analysis the last radiograph was assigned. Subtalar destruction was recorded (Larsen grade > or = 2). Severity of RA in different groups was evaluated using the Larsen score of 0-100 of hands and feet. Difference between patient groups was evaluated using Cuzick's test. RESULTS: At the endpoint major changes of the ankles were detected in seven patients (7%) only, minor changes were observed in 17 patients (16%). The first minor involvement of the ankle was observed at the three-year follow-up in two patients. First major changes were detected at the 15-year follow-up in three ankles of two patients. Subtalar pathology preceded that of TC joint in all ankles with major changes. In 17 patients with minor changes, simultaneous subtalar pathology was observed in all but two ankles, while preceding subtalar involvement was radiographically manifest in 13 of 21 ankles. The means of Larsen scores of 0-100 were in the three ankle grading groups 40, 54 and 63, respectively. Cuzick's test for the trend was highly significant (P < 0.001). No reconstructive surgery was performed on the ankle joint during the follow-up, whereas the subtalar joint complex was fused cumulatively in 12 patients. CONCLUSIONS: The ankle joint is involved in a late stage of RA and is usually affected only in the patients with severe disease. Subtalar pathology precedes the changes in the talocrural joint almost regularly.

Cost-effectiveness of adalimumab, etanercept, and tocilizumab as first-line treatments for moderate-to-severe rheumatoid arthritis.

OBJECTIVE: The aim of this study was to assess the cost-utility and value of reducing the uncertainty associated with the decision to use first-line biologic treatment (bDMARD) after the failure of one or more traditional drugs (tDMARD) in moderate-to-severe rheumatoid arthritis (msRA) in Finland. RESEARCH DESIGN AND METHODS: The treatment sequences were compared among 3000 hypothetical Finnish msRA patients using a probabilistic microsimulation model in a lifetime scenario. Adalimumab + methotrexate, etanercept + methotrexate, or tocilizumab + methotrexate were used as first biologics followed by rituximab + methotrexate and infliximab + methotrexate. Best supportive care (BSC), including tDMARDs, was assumed to be used after the exhaustion of the biologics. Methotrexate alone was added as a further comparator. Efficacy was based on ACR responses that were obtained from a mixed treatment comparison. The resources were valued with Finnish unit costs (year 2010) from the healthcare payer perspective. Additional analyses were carried out, including productivity losses. The Health Assessment Questionnaire (HAQ) values were mapped to the EQ-5D values using the tocilizumab trials; 3% annual discounting for costs and quality-adjusted life years (QALY) and extensive sensitivity analyses were completed. MAIN OUTCOME MEASURES: Incremental cost per QALY gained and multinomial expected value of perfect information (mEVPI). RESULTS: bDMARDs significantly increase the QALYs gained when compared to methotrexate alone. Tocilizumab + methotrexate was more cost-effective than adalimumab + methotrexate or etanercept + methotrexate in comparison with methotrexate alone, and adalimumab + methotrexate was dominated by etanercept + methotraxate. A QALY gained with retail-priced (wholesale-priced) tocilizumab + methotrexate costs €18,957 (€17,057) compared to methotrexate alone. According to the cost-effectiveness efficiency frontier and cost-effectiveness acceptability frontier (CEAF), tocilizumab + methotrexate should be considered before rituximab + methotrexate, infliximab + methotrexate, and BSC. Based on the CEAF, tocilizumab + methotrexate had a 60-93% probability of being cost-effective with €20,000 per QALY gained (mEVPI €230-2182). CONCLUSIONS: Tocilizumab + methotrexate is a potentially cost-effective bDMARD treatment for msRA, indicating a low value of additional research information with the international threshold values. LIMITATIONS: Efficacy based on an indirect comparison (certolizumab pegol, golimumab excluded), fixed treatment sequence after the exhaustion of first bDMARD, Swedish resource use data according to HAQ scores, and inpatient costs assumed to include surgery.

The value of the ACR 1987 criteria in very early rheumatoid arthritis.

We assessed the sensitivity and specificity of the ACR 1987 revised criteria for rheumatoid arthritis (RA) in 121 patients with recent-onset (< or = 6 months) RA, 68 with reactive arthritis (ReA), 19 with ankylosing spondylitis (AS), and 13 with psoriatic arthritis (PsA). The sensitivity of each single criterion ranged 8.3-90.9% and specificity 52.0-100%. The sensitivity of four fulfilled criteria was 83.5% and specificity 86.0%. In ReA 11.8%, AS 5.3%, and PsA 38.5% of patients fulfilled four criteria respectively. Thus at the beginning of RA, 83% of patients could be diagnosed correctly by using the ACR 1987 criteria, and the remaining 17% had seropositive and/or erosive arthritis at the onset. The suitability of the radiographic ACR criteria is discussed.

A 20-year follow-up study of subtalar changes in rheumatoid arthritis.

The destruction of the subtalar joints in 103 seropositive RA patients with recent (< or = 6 months) disease was evaluated radiographically in a prospective follow-up study at onset and at 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15-year follow-up and 68 the 20-year follow-up. The Larsen grades of the joints were evaluated and the need for surgical treatment considered. At the 15-year follow-up the mean Larsen grade was 1.2 (median 0) and at the 20-year follow-up 1.3 (median 0); at the 20-year follow-up 77 subtalar joints were still assessed as Larsen grade 0. In this series, subtalar fusions were performed in 12 patients only. Spontaneous fusions occurred in 5 hindfeet in 3 patients. The destruction rate of the subtalar joint was lower than in previous retrospective or cross-sectional studies. The need for routine radiographs of ankles in RA patients is questioned.

Does wrist fusion cause destruction of the first carpometacarpal joint in rheumatoid arthritis? 18 patients followed for 2-6 years.

We evaluated radiographic destruction of the first carpometacarpal joint (CMC I) in 18 hands with wrist fusions and compared it with the unoperated contralateral hands preoperatively and after a follow-up of a mean of 4.4 (2-6) years. Patients were obtained from a prospective 20-year follow-up study of 103 patients with seropositive rheumatoid arthritis. The degree of destruction in the CMC I-joints was evaluated with Larsen grades. The mean value of Larsen indices for CMC I was 0.9 before wrist fusion and 2.5 (p < 0.001) at the follow-up, compared to 0.8 and 1.3 (p = 0.06) in the control hands, respectively. No preoperative difference was found between the hands to be fused and the control hands, but the difference was significant (p = 0.009) after the follow-up.

Destruction of the first carpometacarpal joint behaves differently from that of the entire carpus in rheumatoid arthritis. A 20-year follow-up study.

The aim of our study was to examine the radiographic changes of the wrist and the first carpometacarpal (CMC I) joints in rheumatoid arthritis (RA) occurring over 20 years. The wrists of 83 RF positive RA patients with recent (< or = 6 months) arthritis were evaluated radiographically at onset, at 1, 3, 8, and 15 years and of 68 patients 20 years from entry. In hands where wrist fusion was performed, follow-up continued until the arthrodesis. Larsen grading for the wrist joints and modified grades for the ipsilateral CMC I joints were compared. Larsen grades of both wrists differed highly significantly (p < 0.001) from the grades of the ipsilateral CMC I joints after 3 years and up to end of the study. In conclusion destruction of the CMC I does not proceed uniformly with destruction of the entire carpus and it would be beneficial to classify it separately.

Coracoclavicular involvement--an atypical manifestation in rheumatoid arthritis.

An inception cohort of 74 patients with seropositive and erosive RA were followed up for 15 years. All 148 shoulders were radiographed with a standard method at the 15-year follow-up. The coracoclavicular region was evaluated from each radiograph. In addition, the distance between the processus coracoideus and the superior margin of the clavicle was measured. Only one clavicle had elongated, shallow erosion on the undersurface at the insertion area of the coracoclavicular ligaments. In this case the distance between the coracoid process and clavicle was 25 mm, whereas the mean distance of all shoulders (n = 148) was 17.4 mm (range 9 25 mm). We conclude that resorption on the undersurface of the distal clavicle is an atypical manifestation in rheumatoid arthritis. The origin of this atypical lesion is a not diminished distance between the processus coracoideus and the clavicle. Inflammation of the coracoclavicular ligaments is most likely the reason for this lesion.

Prevalence of mutilans-like hand deformities in patients with seropositive rheumatoid arthritis. A prospective 20-year study.

This study examined radiographically the prevalence of arthritis mutilans hand deformities in an inception cohort of 68 rheumatoid arthritis (RA) patients. Hand deformities of 103 RF-positive RA patients were evaluated after 8 years, 83 patients after 15 years and 68 patients 20 years after entry. The grade of destruction in the hand joints was assessed by the Larsen method and Larsen scores of 0-50 were determined for both PIP (+IP) and MCP joints. At the end point, 3 patients had Larsen scores > or =40 for both PIP and MCP joints. These three patients had severe resorption in most of the finger joints, but did not demonstrate classical opera-glass hand. The prevalence of mutilans-like hand deformities with RA was 3/68 (4.4%) in a prospective 20-year study.

Increased risk of leukaemia in patients with juvenile chronic arthritis treated with chlorambucil.

Two cases of acute leukaemia have developed in a group of 77 patients treated with chlorambucil (Chl) because of severe juvenile chronic arthritis. The total follow-up from the beginning of Chl treatment in these patients was 560 years, indicating a highly increased risk of leukaemia. Despite favourable results, especially in patients with secondary amyloidosis, Chl should only be used in selected cases.

Radiographic joint space in rheumatoid glenohumeral joints. A 15-year prospective follow-up study in 74 patients.

OBJECTIVE: To evaluate radiographically the glenohumeral (GH) joint space in patients with long-term rheumatoid arthritis (RA). METHODS: A cohort of 74 patients with RA were followed prospectively for 15 yr. At the end point, 148 shoulders were radiographed using a standard method. The GH joint space was examined from the radiographs using a method developed previously for population studies; the joint space was measured at three different sites and the average of the three measurements, the integral space, was calculated. Destruction of the GH joints was assessed with the Larsen method on a scale of 0-5 and compared with the joint space measurements. RESULTS: The mean GH joint space in RA patients was 3. 1 (S.D. 3.3), range -17.3 to 5.7 mm; 2.7 mm (S.D. 4.5) in men and 3. 2 mm (S.D. 2.8) in women. The mean of the affected joints (Larsen grades 2-5), 1.7 mm (S.D. 4.5), was notably narrower than the mean 4. 4 mm (S.D. 0.6) of the non-affected (Larsen grades 0-1) joints. Pathological GH joint space, less than 2 mm, was found in five (15%) of 36 joints in men and in 14 (13%) of 112 joints in women. All the joints graded as Larsen 4 and 5 (n = 17) fulfilled this pathological criterion. Joint space narrowing was associated [r = - 0.66, 95% confidence interval (CI): -0.56 to -0.75] with increasing destruction (Larsen grading) of the joint. The narrowing was significant between non- (Larsen 0, 1), moderately (Larsen 2, 3) and severely (Larsen 4, 5) affected joints (P < 0.001). However, a remarkable step in this process occurred between Larsen grades 3 and 4 when the mean joint space diminished from 3.1 to 0.3 mm. CONCLUSIONS: Joint space narrowing is a frequent consequence of GH joint rheumatoid affection. However, joint space narrowing is a late phenomenon occurring not until after marked erosive destruction, which should be noted when using the Larsen method for GH joints.