Predictive factors related to shoulder joint destruction in rheumatoid arthritis patients treated with biologics: A prospective study

Objective: The aim of this study was to assess the risk factors for shoulder joint destruction in rheumatoid arthritis (RA) patients treated with biologics.

Methods: Thirty shoulders of 29 patients with RA were assessed using 18F-fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) before starting biologics and 6 months later. The mean age (range) was 54 (18–72) years, and the mean disease duration was 7 (0.8–30) years. The radiographic findings were assessed at baseline and 3 years later. The inflammation markers and RA disease activity were also assessed. These parameters were compared between the progression of joint destruction group and the no progression group.

Results: The SUVmax on PET, the rate of synovitis, and the rate of rotator cuff tear on MRI before biologic treatment were significantly higher in the progression of joint destruction group. SUVmax and synovitis on MRI after 6 months were also significantly higher in the progression of joint destruction group. On logistic regression analysis, the SUV at baseline of the shoulder joint was the main risk factor for joint destruction.

Conclusion: The detection of synovitis by imaging was more important than disease activity and inflammation markers for assessing the progression of shoulder joint destruction.     

Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study

OBJECTIVE: To determine prognostic factors for remission in early rheumatoid arthritis. METHODS: 191 patients with rheumatoid arthritis whose disease duration was less than one year were followed up prospectively for five years. Remission, defined by a disease activity score (DAS) of <1.6, was used as the outcome measure. Baseline clinical, laboratory, genetic, and radiographic data (with radiographic scores determined by Sharp's method, modified by van der Heijde) were obtained. RESULTS: 48 patients (25.1%) fulfilled the remission criteria at the three year follow up visit, and 30 (15.7%) at three and five years. On univariate analysis by Fisher's exact test, remission at three years and persistent remission at five years were closely correlated with baseline DAS values, C reactive protein level, Ritchie score, health assessment questionnaire score, duration of morning stiffness, and to a lesser extent baseline total radiological scores and rheumatoid factor negativity. No significant correlation was found with sex, age, extra-articular manifestations, erythrocyte sedimentation rate, anti-cyclic citrullinated protein antibodies, anti-keratin antibodies, anti-HSP 90, anticalpastatin antibodies, antinuclear antibodies, or HLA-DRB1* genotypes. Logistic regression analysis showed that the baseline independent variables predictive of remission were low DAS, Ritchie score, morning stiffness duration, and total radiographic score. CONCLUSIONS: Baseline prognostic factors for remission in early rheumatoid arthritis were mainly clinical markers of disease activity and radiological scores.     

Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study

OBJECTIVE: To determine prognostic factors of radiologic damage and radiologic progression in early rheumatoid arthritis (RA). METHODS: A cohort of 191 patients with RA whose disease duration was shorter than 1 year were prospectively followed up for 3 years. Radiologic scores (as determined by Sharp's method, modified by van der Heijde) and radiologic progression were used as outcome measures. Numerous baseline clinical, laboratory, genetic, and radiographic data were obtained. RESULTS: The change in the total radiologic score for the patients followed up over 3 years was a mean +/- SD increase of 6.1 +/- 6.2. Radiologic progression was observed in 71 of the 172 patients for whom there were data at the end of the study. By univariate analysis with Fisher's exact test, radiologic scores and progression at followup were closely correlated with the baseline values of the erythrocyte sedimentation rate (ESR), C-reactive protein level, IgM and IgA rheumatoid factor positivity, antiperinuclear antibody positivity, radiologic scores, duration of morning stiffness, and RA-associated HLA-DRB1*04 genes. No correlation was demonstrated with sex, age, Disease Activity Score, swollen or tender joint counts, extraarticular manifestations, Health Assessment Questionnaire score, Ritchie Articular Index, patient's assessment of pain, positivity for anti-heat-shock protein 90-kd antibodies, anticalpastatin antibodies, anti-RA33 antibodies, antinuclear antibodies, YKL-40, or antikeratin antibodies, and HLA-DRB1*01 genes. The logistic regression analysis revealed that the only baseline values that were predictive of the 3-year radiologic scores were IgM rheumatoid factor positivity, DRB1*04 genes, pain score, and total radiologic score. Progression of joint damage was predicted by the ESR, IgM rheumatoid factor positivity, DRB1*04 genes, and erosions score at baseline. CONCLUSION: Prognostic factors for radiographic damage in early RA were identified. A combination of these baseline values allowed us to draw up a predictive arithmetic score that could be used to predict radiologic damage at 3 years and radiologic progression in individual patients.     

Frequency and predictors for falls in the ambulatory patients with rheumatoid arthritis: a longitudinal prospective study

The aim of this multicentre study is to investigate the incidence and risk factors for falls in ambulatory rheumatoid arthritis (RA) patients. One hundred and eighty-five ambulatory RA patients who have been followed up in 3 different centres were included in study. Patients were a part of Turkish League Against Rheumatism-Follow-up Program. All patients were evaluated at the baseline in terms of demographic features, falls history in the last year, disease-specific characteristics and co-morbidities. Functional status was evaluated by chair stand test with five repetitions and heel–toe walking. Erythrocyte sedimentation rate and CRP values were measured. Study patients were followed by the three monthly visits during a year. Patients were asked to fill the fall diary and/or call the doctor when a fall happens. The features of falls were recorded to the files at the time of the fall. The mean age was 56.7 ± 11.4 years. Four patients were drop out the study. Thirty-four patients fell and 2 had fractures during 1 year. Falls were found to be correlated with age, visual analogue score for pain, previous falls, use of assistive devices for ambulation, use of two or more medications and ability to do heel–toe walking. In the multivariate regression analysis, previous falls and use of assistive device for ambulation were found to be independent risk factors for falls (p = 0.004 OR 3.3 95 % CI 1.5–7.4, p = 0.001 OR 6.2 95 % CI 2–19.1). Fall history in the last year and using an assistive ambulation device are the predictors of the falls.     

Mechanisms of joint destruction in rheumatoid arthritis

A variety of destructive enzymes are secreted by pannnus. Prominent among these are the various matrix metalloproteinases (MMPs) and cathepsins. These enzymes act upon collagen and the proteoglycan matrix, thereby destroying the central structure of articular cartilage. Other destructive factors include the cytokines TNF-alpha and IL-1, which activate osteoclasts to resorb subchondral bone. A further important mediator is the recently described osteoclast differentiation factor (ODF) (also referred to as TNF-related activation-induced cytokine [TRANCE], receptor activator of nuclear factor kappaB ligand [RANKL], or osteoprotegerin ligand).     

Radiographic study on the pattern of wrist joint destruction in rheumatoid arthritis

When planning therapy for rheumatoid arthritis (RA) in the wrist joint, knowing the pattern of joint destruction is important. There were a few studies using the Larsen and modified Larsen method to evaluate RA wrist joint destruction. However, these methods are inadequate for thoroughly assessing the severity of joint destruction because joint bone erosion and joint space narrowing could not be evaluated individually in these methods. To clarify the pattern of RA wrist joint destruction in the different zones of the wrist, we conducted a large-scale radiographic study. We modified the van der Heijde/Sharp method to assess radiographic images. Subjects were 191 RA patients (22 men and 169 women; mean age 57.0 years) who were examined at our center between 2001 and 2003 and underwent plain X-ray of both wrist joints (n = 382). Using X-ray images of the wrist joint, classification was performed based on the severity of wrist joint surface bone erosion and joint space narrowing at different zones, and the results were statistically analyzed. The results showed that joint space narrowing in the midcarpal joint (MCJ) advanced faster than in the radiocarpal joint (RCJ). Conversely, bone erosion in the RCJ advanced faster than in the MCJ. In X-ray diagnosis of RA wrist joint disorders, knowing the pattern of destruction is useful for assessing the presence or absence of early joint destruction and in planning therapy.     

Prognostic factors in early rheumatoid arthritis

The current paradigm for rheumatoid arthritis suggests that persistent synovitis leads to erosive joint damage, progression of which results in functional disability. Studies of X-ray progression followed for 1-9 yr have shown that 40-83% of subsequent progression can be predicted by a combination of prognostic factors such as joint involvement, high levels of C-reactive protein and rheumatoid factor (RF) positivity. There are similar findings for predictors of functional disability in studies followed for 2-15 yr. The most consistent prognostic feature is RF positivity, which is equally important in predicting joint damage and functional disability. Immunoglobulin A RF and the co-presence of RF with anti-keratin or anti-filaggrin antibodies may increase levels of prediction. Added value of genetic predictors over that of RF remains inconclusive. Therefore, therapeutic management should be individualized. Cases with active disease and seropositive RF tests merit aggressive therapy; conversely, cases with little synovitis and seronegative tests require conservative management.     

Prevention of joint destruction in rheumatoid arthritis by biologics

Increased elucidation of the mechanisms of joint destruction has profoundly shaped the development of anti-cytokine therapies for rheumatoid arthritis (RA). Prevention of joint damage by biologics may successfully avoid functional decline and disability. However, treating physicians must carefully weigh the benefits of biologics against cost and their risks, particularly in patients at risk of the reactivation of tuberculosis.     

Upper airway obstruction in patients with rheumatoid arthritis and temporomandibular joint destruction

Among 400 patients with rheumatoid arthritis and measurable ramus height there were 76 patients with mutilating arthritis of the temporomandibular joints. In 30 of these 400 patients, episodes of upper airway obstruction had occurred, mostly when the patient lay supine. Laryngoscopy had been performed in only 7 patients, and in 3 of those a laryngeal arthritis was detected. Upper airway obstruction had occurred significantly more often in patients with arthritis of the temporomandibular joints than in those with normal joints. In 70% of the patients with a severe arthritic destruction of the temporomandibular joints, episodes of airway obstruction had occurred. Upper airway obstruction is assumed to occur in those patients due to a pharyngeal obstruction, as in other patients with micrognathia or sleep apnea syndrome.     

Associations between the PTPN22 1858C->T polymorphism and radiographic joint destruction in patients with rheumatoid arthritis: results from a 10-year longitudinal study

Objective

To investigate whether the PTPN22 1858T risk variant is associated with the rate of radiographic progression in rheumatoid arthritis (RA).

Methods

A longitudinally followed cohort of 238 Norwegian patients with RA (the EURIDISS cohort) was genotyped for the PTPN22 1858C→T polymorphism. Radiographic damage was assessed by hand radiographs at baseline and after 1, 2, 5 and 10 years, and the radiographs were scored with the Sharp method modified by van der Heijde (Sharp–van der Heijde score) by a single experienced reader. Baseline serum levels of rheumatoid factor and anti‐cyclic citrullinated peptide autoantibodies were also examined.

Results

The reported association between RA susceptibility and carriage of the T allele (34.4% in patients vs 21.4% in controls; odds ratio 1.92, 95% confidence interval 1.36 to 2.71, p = 0.0002) was confirmed. An association between annual progression rate of Sharp–van der Heijde score and T‐allele carriers (p = 0.01),was also found, which was also present when only patients positive for the shared epitope were analysed (p = 0.03). This association was also maintained in multivariate analyses adjusting for shared epitope and demographic variables.

Conclusions

An association between the PTPN22 risk variant and increased progression rate for structural damage was found. The results indicate that the PTPN22 gene may not only be associated with disease susceptibility, but also with disease progression.     

Osteoclastic bone resorption in the joint destruction of rheumatoid arthritis

Osteoclastic bone resorption plays a central role in the joint destruction of rheumatoid arthritis patients. Several bone resorptive cytokines are implied to contribute to the mechanism through induction of RANKL/ODF in synovial cells and/or activated T cells. The target of the RA therapy should be focused on this destructive aspect in relation to the original RA pathophysiology.     

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.     

Significance of rheumatoid factors in an eight-year longitudinal study on arthritis

Summary A community-based cohort comprising 150 patients with recent-onset seropositive arthritis or seronegative oligoarthritis or polyarthritis was monitored for 8 years. Of the different rheumatoid factor (RF) tests, the initial positivity in the most sensitive assays (latex slide test and IgM-RF by enzyme immunoassay) was the most reliable factor when distinguishing between the erosive and nonerosive cases. The individual RF isotypes fluctuated in four serial specimens, but each patient tended to preserve his or her reactivity pattern. Seroconversion from positive to negative within the 1st year of follow-up did not indicate a particularly good long-term prognosis.