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.

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.

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.

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.

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.

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.

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.

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.

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

OBJECTIVE: To evaluate radiographically the humeroulnar (HU) and humeroradial (HR) joint spaces in patients with long-term rheumatoid arthritis (RA). METHODS: An inception cohort of 74 patients with RA were followed for 15 yr. At the end-point, 148 elbows were radiographed by a standard method. The HU and HR joint spaces were examined from the anteroposterior radiographs by measuring the shortest tangential distance in the middle of the joints. Destruction of the elbow joints, assessed with the Larsen method on a scale of 0-5, was studied in relation to the joint-space measurements. RESULTS: Mean (s.d.) HU joint space (n=148) in RA patients was 2.5 (1.1) mm, range 0-4 mm [2.9 (0.8) mm in men and 2.4 (1.1) mm in women]. Mean (s.d.) HR joint space (n=140) was 2.3 (0.9) mm, range 0-4 mm [2.5 (0.8) mm in men and 2.3 (1.0) mm in women]. HU and HR spaces of the affected joints (Larsen grades 2-5) [1.9 (s.d. 1.1) and 1.8 (0.9) mm respectively] were notably narrower than those of the unaffected (Larsen grades 0-1) joints [3.1 (0.7) and 2.9 (0.6) mm]. All the joints graded as Larsen 4 or 5 (n=13) had a value of 0 mm for both joint spaces. Both the HU and the HR joint-space narrowing was associated with increasing destruction (Larsen grading) of the joint. [r= -0.69 (95% CI -0.77 to -0.60) and r= -0.70 (-0.78 to -0.60)]. The monotonic narrowing was significantly increasing from unaffected (Larsen 0, 1), slightly (2), moderately (3) to severely (4, 5) affected joints (P<0.001). A step in this process occurred between Larsen grades 3 and 4, when the mean joint space diminished from 1.4 and 1.5 respectively to 0 mm. CONCLUSIONS: Joint-space narrowing is a frequent consequence of rheumatoid affection of the elbow joint. HR joint space decreases together with HU joint space; however, the HR joint space is already slightly narrower at the start. The narrowing is a rather late phenomenon, occurring only after erosive destruction. This should be borne in mind when using the Larsen method to evaluate changes in the elbow joint.

Valgus deformity and proximal subluxation of the rheumatoid elbow: a radiographic 15 year follow up study of 148 elbows.

OBJECTIVE: To evaluate the nature of positional changes of humeroulnar (HU) and humeroradial (HR) joints in a cohort of 74 patients with seropositive and erosive rheumatoid arthritis (RA) followed up prospectively. METHODS: At the 15 year follow up standard anteroposterior and lateral radiographs of 148 elbow joints were evaluated. The mediolateral HU angle of the elbow was measured from anteroposterior radiographs. The proximal subluxation of the HU joint was measured from lateral radiographs as the distance between the posterior aspect of the olecranon process and the posterior surface of the humerus. The anteroposterior subluxation of the HR joint was measured from lateral radiographs as the relation of the midpoint of head of the radius to the midpoint of the capitellum of the humerus. Destruction of the elbow joints was assessed with the Larsen method on a scale of 0 to 5 and compared with the measurements. RESULTS: Mean HU angle in 148 elbows of patients with RA was 11.5 degrees (SD 6.1), range -21 degrees (varus) to 34 degrees (valgus); 9.9 degrees (SD 4.3) in men and 12.0 degrees (SD 6.4) in women. The mean HU angle, 14.4 degrees (SD 6.0) of the affected joints (Larsen grades 2-4), showed more valgus than the mean 9.8 degrees (SD 2.5) of the non-affected (Larsen grades 0 to 1) joints; totally destroyed and unstable Larsen 5 joints were excluded. Mean HU and HR subluxations, 2.0 mm (SD 3.8) and 0.8 mm, of the affected joints (Larsen 2-5) were greater than the means, -1.1 mm (SD 1.5) and -0.4 mm (SD 0.9), of the non-affected joints. Both the HU proximal subluxation and the HR anterior subluxation correlated, r(s)=0.64 (95% CI 0.53 to 0.73 ) and r(s)=0.48 (95% CI 0.34 to 0.60), with the destruction of the elbow joint. CONCLUSIONS: The elbow seems to turn into valgus during rheumatoid destruction and excision of the radial head may speed up this process. However, totally unstable Larsen grade 5 joints may also have varus deformity owing to mutilating bone destruction. The ulna subluxates proximally in relation to the humerus, whereas the radius moves slightly anteriorly as a consequence of elbow involvement.

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.

Bone destruction, upward migration, and medialisation of rheumatoid shoulder: a 15 year follow up study.

OBJECTIVE: To evaluate bone destruction, upward migration, and medialisation of the glenohumeral (GH) joint in a cohort of 74 patients with seropositive and erosive rheumatoid arthritis followed up prospectively. METHODS: At the 15 year follow up 148 shoulders were radiographed by a standard method. Bone destruction in the GH joint was examined from the radiographs by four methods, of which three measured the migration and one the remodelling of the humeral head. The distances from the greater tuberosity of the humeral head to the coracoid process (medialisation distance (MD)) and to the articular surface of the humeral head (GA) have been previously developed to evaluate the preoperative offsets of the arthritic GH joint. Medial displacement index (MI) and upward migration index (UI) have been recently developed to evaluate the destructive pattern of the rheumatoid GH joint. Destruction of the GH joints was assessed by the Larsen method on a scale of 0 to 5. The relation between the measurements and the grade of destruction of the GH joints was examined. UI was compared with our previous measurements of the subacromial space. RESULTS: Both the MI and the UI had a negative correlation with the GH joint destruction (Larsen grade), r=-0.49 (95% CI -0.36 to -0.60) and r=-0.58 (95% CI -0.46 to -0.68). The UI correlated significantly with the subacromial space, r=0.90 (95% CI 0.86 to 0.93). The mean MI and UI measurements of the non-affected joints were within the reported normal variation. The mean MD collapsed between Larsen grades 4 (83.0 mm) and 5 (65.5 mm). The morphology of the humeral head began to flatten and erode from the grade 3 onwards and medial head destruction was detected at grade 5. CONCLUSIONS: Medialisation seems to be preceded by upward migration of the humeral head, indicating rotator cuff damage. Symptomatic Larsen grade 3 shoulders should be intensively followed up by clinical and radiological means. If a total shoulder arthroplasty is considered, an orthopaedic consultation is worthwhile at a sufficiently early stage (Larsen 3 and 4), when soft tissue structures responsible for function are still in proper condition and timing of the operative procedure can be well planned.

Incidence of elbow involvement in rheumatoid arthritis. A 15 year endpoint study.

OBJECTIVE: To evaluate the incidence of involvement and cause of destruction of humeroulnar (HU) and humeroradial (HR) joints in a prospectively followed cohort of 74 patients with seropositive and erosive rheumatoid arthritis (RA). METHODS: At the 15 year followup standard anteroposterior and lateral radiographs of 148 elbow joints were evaluated, and the grade of destruction was assessed by the Larsen method. RESULTS: Erosive involvement (Larsen grade 2) was observed in 75/148 (51%) elbows in 45/74 (61%) patients; 30 patients had bilateral and 15 unilateral involvement. The incidence of mild erosions (Larsen grade 2) was 49/148 (33%), and severe erosions (Larsen 3-5) 26/148 (18%). The 13 most severely involved (Larsen grade 4-5) joints were seen in 8 (11%) patients. Erosions were most often observed on the capitellum (64 joints) and the lateral epicondyle (58 joints) of the humerus (AP view) or on the olecranon of the ulna (52 joints). The Larsen score (0-100) for peripheral joints correlated significantly with the elbow joint Larsen grade on both sides: right, r = 0.53 (95% CI 0.34 to 0.68); left, r = 0.53 (95% CI 0.34 to 0.68). CONCLUSION: After 15 years more than half of the elbows and almost 2 of 3 patients with RA showed definite involvement of the elbow joint. Erosions were most often located on the capitellum and the lateral epicondyle of the humerus or the olecranon of the ulna. Severe destruction was most often bilateral.

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.

Combination drug therapy retards the development of rheumatoid atlantoaxial subluxations.

OBJECTIVE: To compare the efficacy of combination therapy with disease-modifying antirheumatic drugs (DMARDs) versus single therapy with DMARDs in the prevention of early cervical spine changes in patients with rheumatoid arthritis (RA). METHODS: One hundred ninety-five patients with recent-onset RA (mean disease duration 8 months) were randomly assigned to receive a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single DMARD with or without prednisolone. After 2 years of followup, cervical spine radiographs were taken of 176 of these patients (85 in the combination-therapy group and 91 in the single-therapy group). These radiographs were evaluated, and the findings were correlated with the therapy strategies as well as with peripheral joint destruction and clinical and laboratory variables describing the disease activity. RESULTS: Anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI; i.e., vertical subluxation), and subaxial subluxation (SAS) were found in only 6 (3.4%), 2 (1.1%), and 5 (2.8%) of the patients, respectively. Interestingly, none of the patients in the combination-therapy group had aAAS or AAI. The incidences of aAAS and AAI in the single-therapy group were 6.6% and 2.2%, respectively. SAS was present in 2 patients (2.2%) in the single-therapy group and in 3 patients (3.5%) in the combination-therapy group. The difference in the incidence of aAAS between the treatment groups was statistically significant (P = 0.029). None of the patients with cervical spine changes achieved remission of RA during the study. CONCLUSION: In the present study, the incidence of cervical spine subluxations in patients treated with single-drug therapy was in accord with findings of previous studies. However, none of the patients in the combination-therapy group had aAAS or AAI. These findings suggest that early, aggressive combination-DMARD therapy with sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone can prevent or retard the development of rheumatoid atlantoaxial disorders.

Subacromial space in the rheumatoid shoulder: a radiographic 15-year follow-up study of 148 shoulders.

A cohort of 74 patients with rheumatoid arthritis was monitored prospectively for 15 years. At the end of the study 148 shoulders were radiographed with a standard method. The subacromial space was examined from the radiographs with a method where the acromiohumeral interval was measured from the dense cortical bone marking the inferior aspect of the acromion to a point directly above the head of the humerus. The smallest distance was recorded, and negative values were used when the original articular surface of the humerus exceeded the inferior surface of the acromion. Destruction of the glenohumeral (GH) joints was assessed by the Larsen method on a scale of 0 to 5. The relation of subacromial space measurement to the grade of destruction of GH joints was examined. The mean subacromial space was 6.7 (SD 4.4), range from -13 to 12 mm: 6.1 mm (SD 5.6) in men and 6.9 mm (SD 4.0) in women. The mean of nonaffected (Larsen grade 0 or 1) shoulders (n = 77) was 8.6 mm (SD 1.5), and the corresponding mean of the affected (Larsen grade > or =2) shoulders (n = 71) was 4.6 mm (SD 5.5). Previously reported pathologic criterion (<6 mm) indicating rotator cuff involvement was fulfilled in 30 (20%) of 148 shoulders: in 8 (22%) of 36 shoulders in men and in 22 (20%) of 112 shoulders in women. All the shoulders with severe rheumatoid destruction (Larsen grade 4 or 5) fulfilled the pathologic limit. The subacromial space had a significant negative correlation with the GH joint destruction (Larsen grade) in both sides: right r = -.63 (95% CI -.75 to -.47), left r = -.71 (95% CI -.81 to -.58). Progressive upward migration is an inevitable consequence of rheumatoid destruction in the GH joint. A significant step in this process occurred between the Larsen grades of 3 and 4, where the mean distance turned negative, indicating rotator cuff disease. A patient with rheumatoid arthritis and painful shoulder and upward migration of the humerus on the shoulder radiograph should be evaluated by an orthopaedic surgeon. In indistinct cases with subacromial space diminution, imaging techniques like ultrasonography or magnetic resonance imaging may be required to determine the exact pathologic condition of the rotator cuff and to select optimal treatment.

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.