Multidisciplinary Management of Phyllodes Tumours and Breast Sarcoma: A Cross-sectional Survey of Clinical Practice across the UK and Ireland.

AIMS: Phyllodes tumours and breast sarcomas are uncommon tumours and their rarity poses significant challenges in diagnosis and management. This cross-sectional study was conducted to evaluate the multidisciplinary clinical practice for these tumours across the UK and Ireland, with the aim of identifying gaps in knowledge and providing direction for establishing national guidelines. MATERIALS AND METHODS: An international survey was adapted and circulated to breast and/or sarcoma surgeons and oncologists in the UK and Ireland through national organisations. Multidisciplinary team (MDT) responses were analysed anonymously. RESULTS: Twenty-eight MDTs participated in this study, predominately from high-volume units (85.5%). Although only 43% of the surveyed units were part of a trust that holds a sarcoma MDT, 68% of units managed malignant phyllodes and angiosarcoma, whereas 64.5% managed soft-tissue sarcoma of the breast. Across all subtypes, axillary surgery was recommended by 14-21% of the MDTs and the most recommended resection margins for breast surgery were 'no tumour on ink' in benign phyllodes (39%) and 10 mm in the remaining subtypes (25-29%). Immediate breast reconstruction was supported by 11-18% of MDTs for breast sarcoma subtypes, whereas 36% and 32% advocated this approach in benign and borderline phyllodes tumours, respectively. Adjuvant radiotherapy and chemotherapy were recommended by up to 29% and 11% of the MDTs, respectively. CONCLUSION: The results of this study demonstrate a wide variation in clinical practice across the surveyed MDTs. As only 28 MDTs participated in our study, with under-representation from low-volume units, our results might be an underestimation of the variability in practice across the UK and Ireland. This multi-institutional study sheds light on controversial aspects in the management of phyllodes tumours and breast sarcoma, identifies the need for national guidelines to inform best practice, and calls for the centralisation of the management of breast sarcoma within specialist centres.

Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis: what is the role of inflammation control?

OBJECTIVE: While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. METHOD: Bionaïve PsA patients starting a first anti-TNF therapy 2004-2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. RESULTS: Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator's global assessment were associated with a lower risk of 12-month refractory pain. CONCLUSIONS: A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.

Comparison of chronic widespread pain prevalence with different criteria in two cohorts of rheumatoid arthritis.

OBJECTIVE: This study aims to investigate chronic widespread pain with the 1990 (CWP1990) and 2019 (CWP2019) definitions 6 years after the onset of rheumatoid arthritis (RA), in one patient cohort with tight controls and one conventional cohort, and factors associated with reporting CWP1990 and CWP2019, respectively. METHODS: A cohort of 80 RA patients with monthly visits to the physician the first 6 months was compared to a cohort of 101 patients from the same clinic with conventional follow-up. Both cohorts had early RA (< 13 months). The prevalence of CWP1990 and the more stringent CWP2019 were in a 6-year follow-up investigated with a questionnaire, including a pain mannequin and a fear-avoidance beliefs questionnaire. RESULTS: In the tight control cohort, 10% reported CWP2019 after 6 years compared to 23% in the conventional cohort (p = 0.026). There was no difference when using the CWP1990 definition (27% vs 31%, p = 0.546). When adjusted for important baseline data, the odds ratio for having CWP2019 was 2.57 (95% CI 1.02-6.50), in the conventional group compared to the tight control group (p = 0.046). A high level of fear-avoidance behaviour towards physical activity was associated with CWP2019, OR 10.66 (95% CI 1.01-112.14), but not with CWP1990 in the tight control cohort. CONCLUSION: A more stringent definition of CWP identifies patients with a more serious pain condition, which potentially could be prevented by an initial tight control management. Besides tight control, caregivers should pay attention to fear-avoidance behaviour and tailor treatment. KEY POINTS: • CWP2019 is a more stringent definition of chronic widespread pain and identifies patients with a more serious pain condition. • Patients with a serious pain condition could be helped by frequent follow-ups. • This study suggests that a special attention of fear-avoidance behaviour towards physical activity in patients with RA is needed.

Risk factors for post-operative complications after sentinel lymph node biopsy for cutaneous melanoma: Results from a large cohort study.

BACKGROUND: A sentinel lymph node (SLN) biopsy is a common surgical procedure for cutaneous melanoma. Our aim was to evaluate risk factors for early post-operative complications after SLN biopsy and to examine the impact of complications on health care resource utilisation. METHODS: We performed a retrospective cohort study including all adult patients who underwent a SLN biopsy for cutaneous melanoma in the Stockholm region from 2006 to 2014. Data of patient and tumour characteristics were collected from medical records, as well as information on complications and outpatient visits within 30 days from surgery. Risk factors were evaluated through logistic regression. RESULTS: Out of 886 patients who underwent SLN biopsy during the study period, 109 (12.3%) had one or several post-operative complications. The most common complication was a wound infection (7.7%), followed by seroma (6.4%). The risk of a post-operative complication was increased in patients with diabetes (odds ratio (OR) = 10.0, 95% confidence interval (CI) 4.0-24.6), who had inguinal location of SLN (OR = 2.7, 95% CI 1.7-4.3), who were male (OR = 1.9, 95% CI 1.2-2.9) and who had ulceration of the primary tumour (OR = 1.6, 95% CI 1.0-2.6). Individuals with post-operative complications had more visits to the outpatient clinic (p < 0.05). CONCLUSION: Complications after SLN biopsy affect 12.3% of patients. Our results suggest that patients with diabetes, who had inguinal SLN biopsy and who were male have increased risk, and this might warrant more intense post-operative surveillance.

Risk factors for development and persistence of chronic widespread pain in spondyloarthritis: a population-based two-year follow-up study.

Objective: To study chronic widespread pain (CWP) over time in patients with spondyloarthritis (SpA), and to identify risk factors for development and persistence of CWP.Methods: In this cohort study with baseline and 2.5 year follow-up postal surveys, patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (USpA) (47% women) answered questions regarding pain, and were categorized as no chronic pain (NCP), chronic regional pain (CRP), or CWP. For each risk factor candidate (disease duration, body mass index, smoking, and patient-reported outcome measures), logistic regression analyses with CWP as the main outcome were performed separately, together with a basic model including age, gender, and SpA subgroup.Results: Altogether, 644 patients could be categorized at both time-points, yielding similar prevalence estimates at baseline and follow-up, although 38% transitioned between pain groups. Risk factors (odds ratio; 95% confidence interval) for development of CWP included more pain regions (1.36; 1.20‒1.53), higher pain intensity (1.35; 1.20‒1.52), worse fatigue (1.25; 1.13‒1.38), and worse global health (1.35; 1.19‒1.54). Persistent CWP was reported by 72%. In addition to factors predicting development of CWP, higher age (1.02; 1.00‒1.04), female gender (1.82; 1.06‒3.10), and anxiety (1.07; 1.00-1.14) also predicted persistence.Conclusion: The prevalence of CWP remained high over time, but with individual transitions between the pain groups. The development and persistence of CWP were predicted by more pain and worse health, with the addition of female gender and higher age for persistent CWP. Special attention and treatment alternatives for patients with SpA and concomitant CWP are essential in the clinic.

Intensive care admissions due to poisoning.

BACKGROUND: Poisoning represents a significant part of admissions to intensive care units. The aim of this nationwide study was to describe recent national quality register data of demographics and mortality for these patients. METHOD: A retrospective national observational study including all patients over 19 years admitted to an ICU in Sweden, between 1 January 2010 and 31 December 2011, with an ICD-10 code for poisoning. The data were collected from three national registers (The Swedish Intensive Care Register, The National Patient Register, and The Cause of Death Register). RESULTS: The incidence of ICU-treated poisonings was 43/100,000. Twenty-one per cent (n = 8155) of all poisoned patients seeking medical care were admitted to the ICU. Their median age was 38 years (q1-q3: 26-51), as many men as women and 46.5% (n = 3790) had a previous registered poisoning. A mix of different substances was the most common type of suspected poisoning (29.7%, n = 2424). The in-hospital mortality was 1.9% and was correlated to invasive mechanical ventilation (OR 6.91 CI 95% 4.59-10.42), age > 40 (OR 4.54 CI 95% 2.86-7.21) and no previous hospitalisation for poisoning (OR 3.23 CI 95% 2.06-5.07). For 78.3% (n = 119) of the deceased patients, the fatal poisoning was their first diagnosed poisoning. The 30-day mortality was 2.7%, a majority died from poisoning (P < 0.01). CONCLUSION: In Sweden, patients treated in the ICU due to poisoning represent a fifth of all poisoned patients seeking medical care. Older men with no previous poisoning were considered a high-risk group.

Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells.

Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis. Caveolin-1 overexpression inhibits protein internalization, suggesting a general negative regulatory role of caveolin-1 in endocytosis. In contrast to this global inhibitory effect, we identify several proteins that can override caveolin-1 negative regulation, exhibiting increased internalization at hypoxia. We demonstrate antibody-mediated cytotoxin delivery and killing specifically of hypoxic cells through one of these proteins, carbonic anhydrase IX. Our data reveal that caveolin-1 modulates cell-surface proteome turnover at hypoxia with potential implications for specific targeting of the hypoxic tumour microenvironment.

Smoking as a risk factor for the radiological severity of rheumatoid arthritis: a study on six cohorts.

BACKGROUND: Smoking is a risk factor for the development of anti -citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA). Whether smoking predisposes to severe joint damage progression is not known, since deleterious, protective and neutral observations have been made. OBJECTIVE: To determine the effect of smoking on joint damage progression. METHODS: Smoking status was assessed in 3158 RA patients included in six cohorts (Leiden Early Arthritis Clinic (Leiden-EAC), BARFOT, Lund, Iceland, NDB and Wichita). In total 9412 radiographs were assessed. Multivariate normal regression and linear regression analyses were performed. Data were summarised in a random effects inverse variance meta-analysis. RESULTS: When comparing radiological progression for RA patients that were never, past and current smokers, smoking was significantly associated with more severe joint damage in Leiden-EAC (p=0.042) and BARFOT (p=0.015) RA patients. No significant associations were found in the other cohorts, though a meta-analysis on the six cohorts showed significantly more severe joint damage progression in smokers (p=0.01). Since smoking predisposes to ACPA, analyses were repeated with ACPA as additional adjustment factor. Then the association was lost (meta-analysis p=0.29). CONCLUSIONS: This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.

Association of genetic variants in the IL4 and IL4R genes with the severity of joint damage in rheumatoid arthritis: a study in seven cohorts.

OBJECTIVE: The progression of joint destruction in rheumatoid arthritis (RA) is determined by genetic factors. Changes in IL4 and IL4R genes have been associated with RA severity, but this finding has not been replicated. This study was undertaken to investigate the association between IL4- and IL4R-tagging single-nucleotide polymorphisms (SNPs) and the progression rate of joint damage in RA in a multicohort candidate gene study. METHODS: IL4- and IL4R-tagging SNPs (n = 8 and 39, respectively) were genotyped in 600 RA patients for whom 2,846 sets of radiographs of the hands and feet were obtained during 7 years of followup. Subsequently, SNPs significantly associated with the progression of joint damage were genotyped and studied in relation to 3,415 radiographs of 1,953 RA patients; these included data sets from Groningen (The Netherlands), Lund (Sweden), Sheffield (UK), the North American Rheumatoid Arthritis Consortium (US), Wichita (US), and the National Data Bank (US). The relative increase in progression rate per year in the presence of a genotype was determined in each cohort. An inverse variance weighting meta-analysis was performed on the 6 data sets that together formed the replication phase. RESULTS: In the discovery phase, none of the IL4 SNPs and 7 of the IL4R SNPs were significantly associated with the joint damage progression rate. In the replication phase, 2 SNPs in the IL4R gene were significantly associated with the joint damage progression rate (rs1805011 [P = 0.02] and rs1119132 [P = 0.001]). CONCLUSION: Genetic variants in IL4R were identified, and their association with the progression rate of joint damage in RA was independently replicated.

A genetic variant in granzyme B is associated with progression of joint destruction in rheumatoid arthritis.

OBJECTIVE: Genetic factors account for an estimated 45-58% of the variance in joint destruction in rheumatoid arthritis (RA). The serine proteinase granzyme B induces target cell apoptosis, and several in vitro studies suggest that granzyme B is involved in apoptosis of chondrocytes. Serum levels of granzyme B are increased in RA and are also associated with radiographic erosions. The aim of this study was to investigate GZMB as a candidate gene accounting for the severity of joint destruction in RA. METHODS: A total of 1,418 patients with 4,885 radiograph sets of the hands and feet from 4 independent cohorts were studied. First, explorative analyses were performed in 600 RA patients in the Leiden Early Arthritis Clinic cohort. Fifteen single-nucleotide polymorphisms (SNPs) tagging GZMB were tested. Significantly associated SNPs were genotyped in data sets representing patients from the Groningen, Sheffield, and Lund cohorts. In each data set, the relative increase in the annual rate of progression in the presence of a genotype was assessed. Data were summarized in a meta-analysis. The association of GZMB with the RNA expression level of the GZMB genomic region was tested by mapping expression quantitative trait loci (QTLs) on 1,469 whole blood samples. RESULTS: SNP rs8192916 was significantly associated with the rate of joint destruction in the first cohort and in the meta-analysis of all data sets. Patients homozygous for the minor allele of rs8192916 had a higher rate of joint destruction per year compared with other patients (P = 7.8 × 10(-4)). Expression QTL of GZMB identified higher expression in the presence of the minor allele of rs8192916 (P = 2.27 × 10(-5)). CONCLUSION: SNP rs8192916 located in GZMB is associated with the progression of joint destruction in RA as well as with RNA expression in whole blood.

Genetic variants in IL15 associate with progression of joint destruction in rheumatoid arthritis: a multicohort study.

BACKGROUND: Interleukin (IL)-15 levels are increased in serum, synovium and bone marrow of patients with rheumatoid arthritis (RA). IL-15 influences both the innate and the adaptive immune response; its major role is activation and proliferation of T cells. There are also emerging data that IL-15 affects osteoclastogenesis. The authors investigated the association of genetic variants in IL15 with the rate of joint destruction in RA. METHOD: 1418 patients with 4885 x-ray sets of both hands and feet of four independent data sets were studied. First, explorative analyses were performed on 600 patients with early RA enrolled in the Leiden Early Arthritis Clinic. Twenty-five single-nucleotide polymorphisms (SNPs) tagging IL-15 were tested. Second, SNPs with significant associations in the explorative phase were genotyped in data sets from Groningen, Sheffield and Lund. In each data set, the relative increase of the progression rate per year in the presence of a genotype was assessed. Subsequently, data were summarised in an inverse weighting meta-analysis. RESULTS: Five SNPs were significantly associated with rate of joint destruction in phase 1 and typed in the other data sets. Patients homozygous for rs7667746, rs7665842, rs2322182, rs6821171 and rs4371699 had respectively 0.94-, 1.04-, 1.09-, 1.09- and 1.09-fold rate of joint destruction compared to other patients (p=4.0×10(-6), p=3.8×10(-4), p=5.0×10(-3), p=5.0×10(-3) and p=9.4×10(-3)). DISCUSSION: Independent replication was not obtained, possibly due to insufficient power. Meta-analyses of all data sets combined resulted in significant results for four SNPs (rs7667746, p<0.001; rs7665842, p<0.001; rs4371699, p=0.01; rs6821171, p=0.01). These SNPs were also significant after correction for multiple testing. CONCLUSION: Genetic variants in IL-15 are associated with progression of joint destruction in RA.

Long-term mortality rate in rheumatoid arthritis patients with disease onset in the 1980s.

OBJECTIVE: To investigate the mortality rate and possible early predictive factors of mortality after 19-23 years in a cohort of patients with rheumatoid arthritis (RA) followed prospectively from disease onset. PATIENTS AND METHODS: A community-based cohort of 183 patients (63% female) with RA and disease duration < 2 years was recruited 1985-1989. The patients were followed yearly from diagnosis until death or 31 December 2008. Mean age and mean duration of symptoms (range) at diagnosis were 52 (18-78) years and 11 (0-24) months, respectively. Death certificates were obtained from the Swedish Cause of Death Register and causes of death were coded by the International Classification of Diseases (ICD-10). Death rates of RA patients were compared to those of age- and sex-matched controls. Possible predictors of mortality were analysed using a Cox regression model. RESULTS: By 31 December 2008, 69 patients (37 women and 32 men) had died. The standardized mortality ratio (SMR) was 1.23 [95% confidence interval (CI) 0.97-1.55] and p < 0.09. Older age, male sex, smoking, and the presence of cardiovascular disease (CVD) at RA diagnosis were identified as early predictors of mortality. CVD was the most common cause of death (46%), followed by malignancies (29%) and infections (13%). RA was not stated as the direct cause of death in any patient and was mentioned among underlying causes in only 16/69 (23%) patients. CONCLUSION: Mortality rate after 19-23 years of disease duration in this cohort of patients with disease onset in the 1980s was not significantly increased compared to age- and sex-matched controls. No RA disease-related factor predicted mortality.

Prevalence and predictive factors of comorbidity in rheumatoid arthritis patients monitored prospectively from disease onset up to 20 years: lack of association between inflammation and cardiovascular disease.

OBJECTIVES: To study the prevalence of comorbid conditions at diagnosis and during follow-up in a cohort of patients with early rheumatoid arthritis (RA) followed prospectively over 20 years, and to identify possible early predictive factors for future comorbidities. METHODS: A community-based cohort of 183 patients (mean age 52 years, 63% female) with early RA was recruited between 1985 and 1989. The presence of comorbidity at RA diagnosis and the occurrence of additional comorbidities were recorded continuously. Possible predictors of future comorbidities were analysed using the Cox proportional hazards model. RESULTS: At RA diagnosis, at least one comorbid condition was present in 43% of the patients. Cardiovascular diseases (CVDs), including hypertension (16% of patients) and malignancy (6% of patients), were most common. In total, 82% of patients developed additional comorbidities during follow-up. CVD and malignancies remained the most frequent comorbidities. Higher age [p < 0.001, odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01­1.15] and the presence of any comorbidity at diagnosis (p = 0.02; OR 1.64, 95% CI 1.08­2.52) predicted future comorbidity. Measures of inflammation at diagnosis or during follow-up were not predictive for development of CVD. CONCLUSION: Comorbidity was present in a considerable proportion of patients in this cohort. More than 40% of patients had another disease at inclusion and during follow-up and > 80% developed additional conditions. The pattern of comorbidity remained unchanged, with CVD and malignancy being most common. Older age and the presence of comorbidity at RA diagnosis predicted the development of comorbidities. The degree of inflammation at any time point was not predictive of future CVD.

MitoPark mice mirror the slow progression of key symptoms and L-DOPA response in Parkinson's disease.

The MitoPark mouse, in which the mitochondrial transcription factor Tfam is selectively removed in midbrain dopamine (DA) neurons, is a genetic model for Parkinson's disease (PD) that replicates the slow and progressive development of key symptoms. To further validate this model, we have extended both behavioral and biochemical analyses in these animals. We found that vertical movements decline earlier and faster than horizontal movements, possibly modeling the early occurrence of axial, postural instability in PD. L-DOPA induces different locomotor responses depending on the age: in young MitoPark mice the L-DOPA-induced motor activation is small; middle-aged MitoPark mice respond in a dose-dependent manner to L-DOPA, whereas aged MitoPark mice display a double-peaked locomotor response to a high dose of L-DOPA that includes an intermittent period of very low motor activity, similar to the 'on-off' phenomenon in PD. To correlate behavior with biochemical data, we analyzed monoamine levels in three different brain areas that are highly innervated by the DA system: striatum, anterior cortex and olfactory bulb. DA levels declined earlier and faster in striatum than in cortex; only at the latest time-point analyzed, DA levels were found to be significantly lower than control levels in the olfactory bulb. Interestingly, the ratio between homovanillic acid (HVA) and DA differed between regions over time. In striatum and olfactory bulb, the ratio increased steeply indicating increased DA turnover. In contrast, the ratio decreased over time in cortex, revealing important differences between DA cells in substantia nigra and the ventral tegmental area.

Orthopaedic surgery in patients with rheumatoid arthritis over 20 years: prevalence and predictive factors of large joint replacement.

OBJECTIVE: To study the prevalence of orthopaedic surgery and to evaluate possible predictive factors for large joint replacements in patients with early rheumatoid arthritis (RA). PATIENTS AND METHODS: A cohort of 183 patients (116 (63.4%) female) with early RA was monitored for 16-20 years after recruitment during 1985-9. Mean (SD) age of patients 51.4 (12.4) years; mean (SD) duration of symptoms before inclusion 12 (7) months and mean (SD) duration of follow-up 16 (4) years. Occurrence of orthopaedic surgery was recorded continuously. A first prosthesis of a large joint (shoulder, elbow, wrist, hip, knee or ankle) was used as outcome variable in the predictive analyses. RESULTS: In total, 386 orthopaedic interventions were performed in 106/183 (58%) patients during follow-up and a large joint replacement was performed in 44/183 (24%) patients. Using a Cox regression model, it was shown that Health Assessment Questionnaire, C-reactive protein and erythrocyte sedimentation rate at inclusion, and radiographic changes in small joints after 1 year, were associated with an increased risk of receiving prosthesis of large joints. CONCLUSION: In this cohort of patients with RA monitored from early disease stage, orthopaedic surgical procedures were performed in more than half of the patients. This included first large joint replacements in 24% of the cases. Easily available measures were identified as predictors of such joint replacements. This study could serve as a reference for comparison with cohorts of patients with RA recruited today, in which new more efficacious treatments are used.

Prognostic laboratory markers of joint damage in rheumatoid arthritis.

OBJECTIVE: To investigate whether determination of a set of laboratory markers at baseline provides prognostic information on joint damage in hands and feet in rheumatoid arthritis. METHODS: 183 patients with early rheumatoid arthritis included in a prospective study were examined. Radiographic changes in hands and feet at 5 and 10 years after inclusion were evaluated (Larsen). The markers analysed were: erythrocyte sedimentation rate (ESR); HLA-DRB alleles typed by restriction fragment length polymorphism; and C reactive protein, cartilage oligomeric matrix protein (COMP), rheumatoid factor (RF) (IgG, IgA, and IgM subtypes), antibodies against cyclic citrullinated peptide (anti-CCP), and antibodies against interleukin 1alpha (anti-IL1alpha), analysed by immunoassays. Multiple linear regression with backward elimination was used to determine the prognostic value of the variables. RESULTS: 117/176 patients were positive for IgG RF, 138/176 for IgA RF, 139/176 for IgM RF, 140/176 for anti-CCP, and 40/182 for anti-IL1alpha. After five years, ESR, the presence of IgA RF, serum COMP, and the presence of anti-CCP were significantly associated with more severe joint damage, and the presence of anti-IL1alpha with less severe joint damage. Baseline C reactive protein and anti-CCP predicted radiographic outcome after 10 years. A stronger prediction was obtained by combining the prognostic factors. CONCLUSIONS: Early determination of anti-CCP, IgA RF, anti-IL-1alpha, ESR, C reactive protein, and COMP predicted the development of joint damage in hands and feet in this cohort. A combination of these measures reflecting different aspects of the disease process should be useful for evaluating prognosis in individual patients with early rheumatoid arthritis.

Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis.

OBJECTIVE: To investigate development of radiographic damage in hands and feet of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years, and to search for prognostic factors. PATIENTS AND METHODS: 181 patients with early RA (mean disease duration one year) were assessed annually with radiographs of hands and feet during years 0-5 and at year 10. Radiographs were evaluated according to Larsen (range 0-200). Predictive factors for progressive disease for years 0-5 and 5-10 were evaluated by logistic regression analyses. RESULTS: 82/168 (49%) patients had erosions at inclusion and almost all became erosive with time (90% after two years and 96% after 10 years). Radiographic progression was most rapid during the first two years and 75% of all damage occurred during the first five years. The median Larsen score increased from 6 at inclusion to 41 after five years and 54 after 10 years. Only 5.3% of all evaluated joints became maximally eroded, the second metacarpophalangeal joint being the most commonly affected. Mean ESR during the first three months and rheumatoid factor status were significant predictors for radiographic progressive disease, it was not possible to predict non-progressive disease. CONCLUSIONS: Joint damage in hands and feet developed early and progression was most rapid during the first years of disease. The different rates of progression at different stages should be considered in the design of trials of drugs aimed at retarding joint damage. Disease activity at study start influenced the degree of joint damage during the entire 10 years.

Ten year outcome in a cohort of patients with early rheumatoid arthritis: health status, disease process, and damage.

OBJECTIVE: To investigate outcome as measured by health status, disease process, and damage in an unselected group of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years and to search for prognostic factors. PATIENTS AND METHODS: 183 patients with RA with disease duration <2 years were assessed annually at a team care unit. Health status was measured by the Health Assessment Questionnaire (HAQ) and functional class. Disease process was assessed by clinical and laboratory measures of disease activity and evaluation of disease course. Damage was quantified as occurrence of major extra-articular manifestations and need for large joint replacements. Possible predictive factors were evaluated by logistic regression analyses. RESULTS: 168/183 patients completed the entire follow up period. Of all 183 patients, 137 (75%) had been treated with disease modifying antirheumatic drugs and 84 (46%) with low dose oral glucocorticoids. After 10 years 158 patients (94%) managed daily life activities independently (functional class I-II). As measured by the HAQ 20% had almost no disability, 28% were mildly disabled, and 10% were seriously disabled. Median HAQ score had increased from 0.8 to 1.1 (p<0.001). Disease activity was significantly reduced. 133 patients (79%) had a relapsing remitting disease course and 30 patients (18%) were in remission as defined by the American College of Rheumatology criteria. Thirty patients (17%) had undergone large joint replacements. Fifteen patients (8%) had developed major extra-articular complications. The HAQ score during the first three months predicted disability at 10 years with an odds ratio of 13.4. CONCLUSIONS: Prospective studies such as this give important knowledge of the variable long term prognosis of RA and provide necessary background information for clinical trials of new treatment modalities.