H.J. Bernelot Moens

No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis

OBJECTIVE To evaluate the cyclosporin A (CSA)-attributed risk of developing malignancies in general and malignant lymphoproliferative diseases (LPDs) and skin cancers in particular, as well as the CSA-attributed incidence of mortality in patients with rheumatoid arthritis (RA). METHODS In a retrospective, controlled cohort study, the incidence of malignancies and mortality was evaluated in 208 CSA-treated patients with RA compared with 415 matched control patients with RA between 1984 and 1995. Patients were followed up for a median of 5.0 years (range 1.4-12.0). RESULTS Forty-eight cases of malignancy (8 in the CSA group and 40 in the control group; relative risk [RR] 0.40, 95% confidence interval [95% CI] 0.19-0.84) were identified, of which 8 were malignant LPDs (2 CSA versus 6 control; RR 0.67, 95% CI 0.14-3.27) and 14 were skin cancers (2 CSA versus 12 control; RR 0.33, 95% CI 0.08-1.47). Seventy-three patients died (16 CSA versus 57 control; RR 0.56, 95% CI 0.33-0.95) due primarily to cardiovascular diseases (4 CSA versus 22 control; RR 0.36, 95% CI 0.13-1.04) or a malignancy (3 CSA versus 8 control; RR 0.67, 95% CI 0.18-2.43). Proportional hazards regression analysis with correction for potential confounding factors did not significantly change the results. CONCLUSION The study findings suggest that CSA treatment in RA patients does not increase the risk of malignancies in general or the risk of malignant LPDs or skin cancers in particular. Moreover, the incidence of mortality in CSA-treated RA patients was comparable to that in matched control RA patients.

Silicone breast prostheses and rheumatic symptoms: a retrospective follow up study.

OBJECTIVES--To determine whether women with silicone breast prostheses have more rheumatic complaints than controls. METHODS--The study included 287 women who had silicone breast prostheses implanted between 1978-90. For every patient a female control of the same age was selected who had had an aesthetic operation in the same year. A questionnaire was sent to this retrospective cohort of women with silicone breast prostheses and controls. RESULTS--Questionnaires were returned by 235 cases (82%) and 210 controls (73%). Patients reported more symptoms arising after surgery than controls (0.6 v 0.3 complaints per subject, p < 0.001). The average interval between surgery and onset of complaints was 5.1 years for patients and 5.9 for controls. Complaints presented by patients were: painful joints (p < 0.005), burning eyes (p < 0.01), and skin abnormalities (p < 0.005). Differences in the use of antirheumatic drugs or medical consultations related to rheumatic symptoms did not reach statistical significance. Further information obtained from the patients and controls reporting rheumatic symptoms did not reveal the presence of a specific syndrome in connection with silicone materials. CONCLUSION--Women with silicone breast prostheses report more rheumatic complaints after silicone implantation than controls, but there is no evidence of increased prevalence of common rheumatic diseases.

The rheumatoid arthritis articular damage score: first steps in developing a clinical index of long term damage in RA

Objective: To design and validate a clinical method for scoring irreversible long term articular damage in rheumatoid arthritis (RA). Methods: The rheumatoid arthritis articular damage score (RAAD score) is based on examination of 35 large and small joints. Concise definitions were formulated to score each joint on a three point scale (0, no irreversible damage; 1, partially damaged; 2, severe damage, ankylosis, or prosthesis). The RAAD score was determined for 121 patients with RA with a large range of disease duration. Interobserver agreement was studied in 39 patients scored by three observers. Data on disease duration, Health Assessment Questionnaire, disease activity score, and Larsen score were collected for 121, 78, 47, and 45 patients, respectively. Results: The RAAD score correlated well with the Larsen score (rs=0.81) and disease duration (rs=0.68) and (as intended) not with disease activity (rs=0.10). Good interobserver agreement was found for total scores and individual joints. The wide range of RAAD scores for patients with the same disease duration suggested good discriminating power, especially after >10 years. Conclusion: The RAAD score is a quick and feasible method for measuring the long term articular damage in large RA populations. It has good reliability and construct validity and deserves further study to assess its discriminant validity.

Antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease: a cost effectiveness analysis

OBJECTIVE To assess the cost effectiveness of antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease. METHODS In a decision analysis, data from a prospective study on bacterial arthritis in 4907 patients with joint disease were combined with literature data to assess risks and benefits of antibiotic prophylaxis. Effectiveness and cost effectiveness calculations were performed on antibiotic prophylaxis for various patient groups. Grouping was based on (a) type of event leading to transient bacteraemia—that is, infections (dermal, respiratory/urinary tract) and invasive medical procedures—and (b) the patients susceptibility to bacterial arthritis which was increased in the presence of rheumatoid arthritis, large joint prostheses, comorbidity, and old age. RESULTS Of the patients with joint disease, 59% had no characteristics that increased susceptibility to bacterial arthritis, and 31% had one. For dermal infections, the effectiveness of antibiotic prophylaxis was maximally 35 quality adjusted life days (QALDs) and the cost effectiveness maximally

Rheumatoid arthritis is not associated with prior tonsillectomy or appendectomy

52 000 per quality adjusted life year (QALY). For other infections, the effectiveness of prophylaxis was lower and the cost effectiveness higher. Prophylaxis for invasive medical procedures seemed to be acceptable only in patients with high susceptibility: 1 QALD at a cost of

FRI0336 Effectiveness of Abatacept, Rituximab or A TNFI after Failure of the First Tnfi: Results of A Multi-Centered Pragmatic Rct

1300/QALY; however, the results were influenced substantially when the level of efficacy of the prophylaxis or cost of prophylactic antibiotics was changed. CONCLUSION Prophylaxis seems to be indicated only for dermal infections, and for infections of the urinary and respiratory tract in patients with increased susceptibility to bacterial arthritis. Prophylaxis for invasive medical procedures, such as dental treatment, may only be indicated for patients with joint disease who are highly susceptible.

AB0743 A hand positioning frame improves joint recognition on hand radiographs

SummaryTo re-evaluate a reported association of rheumatoid arthritis (RA) with antecendent tonsillectomy or appendectomy, questionnaires were sent by post to 3673 patients who had been diagnosed as having either RA or osteoarthrosis (OA). Of those who responded 1524 were RA and 1194 OA patients. No significant differences were found between these groups with regard to the frequency of prior lymphoid surgery. This was also the case when the RA group was replaced by its rheumatoid factor (Rf) positive or Rf negative subgroup. A separate analysis of a subgroup consisting of 671 Rf positive RA patients for whom OA control subjects matched for sex and year of birth were available again showed no statistical differences in frequencies of tonsillectomy and appendectomy. Neither did partitioning the group according to the age at which lymphoid surgery was performed bring any association with an increased occurrence of RA to light. We therefore reject the hypothesis that RA is associated with antecedent tonsillectomy or appendectomy.

Perivascular infiltration in normal skin of patients with rheumatoid arthritis: association with rheumatoid factors and HLA-DR antigens.

Background The most effective biological treatment option after the failure of a first TNFi treatment in a patient with rheumatoid arthritis (RA) is still unknown. Objectives The objective of this study was to compare the effectiveness of three treatment options: abatacept, rituximab and a second TNFi, after the failure of a TNFi treatment, in patients with RA. Methods The inclusion criteria for this pragmatic randomized controlled trial were: failing of the first TNFi, a DAS28 >3.2, not treated before with abatacept or rituximab and no contraindications for these medications. Primary outcome, the DAS28 and the secondary outcomes, HAQ-DI and SF36, were analyzed by linear mixed models to find differences over time. We corrected for possible confounders. Suspected Unexpected Serious Adverse Reactions (SUSAR) and Serious Adverse Reactions (SAR) were collected. Results Of 144 randomized patients, 8 did not start the treatment due to infections, withdrawn from the study or did not want to start the medication. 136 started in one of the three treatment arms; 42 on abatacept (mean age=56.2 yrs, female=88.1%, median disease duration=7.1 yrs, rheumatoid factor (RF) positive=51.4%, mean baseline DAS28=4.7); 44 on rituximab (mean age=56.7 yrs, female=63.6%, median disease duration=7.6 yrs, RF positive=79.1% mean baseline DAS28=4.9); and 50 on a second TNFi (mean age=56.2 yrs, female=74.0%, median disease duration=5.6 yrs, RF positive=55.8% mean baseline DAS28=4.9). Gender and RF are significantly different between the groups (p=0.032 and p=0.020 respectively). The mean DAS28 at 6 and 12 month respectively were 4.05 and 3.85 for abatacept, 3.85 and 3.40 for rituximab and 3.70 and 3.50 for a second TNFi. No significant differences in effectiveness between the three treatment options over time (mixed models) were found in one of the outcome variables. The figure shows the DAS28 and HAQ-DI over time. One SUSAR occurred during one year follow-up. A patient in the abatacept group got a psychosis four months after the start of the study. Three SARs occurred within one year after start of the study: one salmonella infection and one pneumonia in the rituximab group and one pneumonia in the TNFi group. However, these SARs were no reason to change or stop medication. Conclusions Although during a follow up of 1 year some small differences in DAS28, HAQ-DI and SF36 were seen between abatacept, rituximab, and a second TNFi after failure of the first TNFi, these differences were not significant. So if effectiveness is the only interest, abatacept, rituximab and TNFi seem probably equally effective after failure of the first TNFi. No substantial differences with respect to safety were observed between these three treatment groups. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1635

Spa treatment for primary fibromyalgia syndrome: a combination of thalassotherapy, exercise and patient education improves symptoms and quality of life

Background Current clinical scoring methods for hand radiographs in RA are time consuming and subject to intra and inter-reader variance. Several methods for partially automatic radiographic assessment of hand radiographs were proposed [1]. These methods depend on detection (segmentation) of bones and joints. Their success rate is unpublished. We developed a semi-automated pattern recognition method [2]. To model bone shape variation independent from hand positions, this method used connected submodels and an iterative search to find the bones of the hand. These models were combined into a single model of the entire hand. The wide variation in the position of hands on subsequent radiographs was an obstacle in joint recognition and measurement of joint space width. We have therefore developed a positioning frame with 7 pins to reduce positioning error. Objectives Compare the success rate of joint recognition on hand radiographs made without and with a positioning aid. Methods The positioning frame was introduced in 2011 for hand radiographs of RA patients. A random selection of 91 images made before, and 87 made after introduction of the frame was analyzed using the previous described model [2]. Radiographs made with the frame were analyzed with the same model, with the addition to check for correct detection of hands relative to the pins. Processed images are intended for measurements of joint damage and have bone outlines surrounded by boxes. For 14 joints per hand (MCP, PIP, DIP) segmentation was judged by a rheumatologist and considered correct when at least part of the joint space was included in the overlapping boxes around the adjoining bones. Results Conclusions The use of a hand positioning frame improves the performance of previously developed segmentation software for analysis of hand radiographs. This brings us closer to a fully automated system that measures joint damage. Training of the model using a wider range of hands may further improve segmentation. References J.T.Sharp et al, Computer based methods for measurement of joints space width: update of an ongoing OMERACT project, Journal of Rheumatology, 34(4):874-883,2007 J.A.Kauffman et al, Segmentation of hand radiographs by using multi-level connected active appearance models, Proceedings of Medical Imaging2005: Image Processing, 5747:1571-1581,2005 Disclosure of Interest None Declared

Validation of the AI/RHEUM knowledge base with data from consecutive rheumatological outpatients.

The relation between immunohistological findings in biopsy specimens of apparently normal skin, HLA antigens, and rheumatoid factors (RF) was studied in 120 patients with rheumatoid arthritis (RA), selected for treatment with D-penicillamine. Perivascular infiltration (PVI) of more than three mononuclear cells was present in 77 (68%) of 114 patients, accompanied usually by the presence of IgM or C3, or both, in immunofluorescence studies. The number of perivascular cells was associated significantly with the titre of circulating RF. A weak relation of both perivascular cellular infiltration and RF with HLA-DR3 and DR4 did not reach statistical significance. It is concluded that the histological presence of perivascular inflammation is associated mainly with deposition of RF. It is suggested that the first is merely an epiphenomenon of the latter. PVI was not prognostic for the occurrence of the clinical syndrome of rheumatoid vasculitis. For practical purposes skin biopsies do not appear to be useful in the evaluation of individual patients with RA.