Cognitive-behavioural and social factors do not predict recurrent secondary healthcare use in patients with fibromyalgia: a longitudinal study.

OBJECTIVES: Healthcare use in fibromyalgia (FM) is relatively high. Besides disease-related variables, cognitive-behavioural factors have been concurrently associated with healthcare use. It is unknown whether cognitive-behavioural and social factors also predict future healthcare use. The aim of this study was to identify cognitive-behavioural and social factors predicting recurrent secondary healthcare use in FM. METHODS: Using self-reported questionnaires, healthcare use, cognitive-behavioural, social, sociodemographic and disease-related variables including comorbidities were collected in 199 patients with FM, in a prospective longitudinal cohort spanning 18 months. Patients were recruited after receiving their diagnosis and protocolled treatment advice by a rheumatologist. Univariate and multivariate logistic regression models examined whether and which variables were predictors for recurrent secondary healthcare use. Internal validation was performed to correct for over-fit of the final multivariate model. RESULTS: Recurrent secondary healthcare use was lower than initial secondary healthcare use. Univariate analysis showed that having at least one comorbidity, depressive feelings, severe consequences of FM, low personal control and a high severity of fibromyalgia predicted recurrent secondary healthcare use. In the multivariate model, having at least one comorbidity was the only remaining predictor for recurrent secondary healthcare use. CONCLUSIONS: Our results suggest that the existence of comorbidities as communicated by the patient is the strongest warning signal for recurrent secondary healthcare use in FM. There seems no value in using cognitive-behavioural and social factors for early identification of patients with FM at risk for recurrent secondary healthcare use.

Most Important Frequently Asked Questions From Patients With Hip or Knee Osteoarthritis: A Best-Worst Scaling Exercise.

OBJECTIVE: To collect and prioritize the frequently asked questions (FAQs) that patients with hip or knee osteoarthritis (OA) and health care professionals consider to be the most important; to identify informational needs that go beyond guideline recommendations. METHODS: FAQs were collected among health care professionals and from the arthritis helpline of the Dutch Arthritis Foundation. After deleting overlapping FAQs, the remaining FAQs were prioritized by patients and health care professionals using a maximum difference scaling method. A hierarchical Bayesian method was used to calculate relative importance scores. Differences between health care professionals and patients were analyzed using independent t-tests. RESULTS: A total of 28 health care professionals and the arthritis helpline provided 192 FAQs. After deleting overlapping FAQs, 60 FAQs were prioritized by 94 patients (57 [60.6%] women, mean age 67.3 years) and 122 health care professionals (67 [54.9%] women, mean age 45.7 years). The FAQ "What can I do myself to decrease symptoms and to prevent the OA from getting worse?" was prioritized as the most important by both patients and professionals. FAQs that were highly prioritized by patients but significantly different from professionals were more directed toward treatment options offered by health care professionals, whereas highly prioritized FAQs of professionals were more often focused on treatment options involving self-management. CONCLUSION: The health care professionals' perspective on informational needs differs from that of OA patients. These differences are important to address in order to achieve more active involvement of patients in their own treatment process.

Ultra-low doses of rituximab for continued treatment of rheumatoid arthritis (REDO study): a randomised controlled non-inferiority trial.

BACKGROUND: Rituximab is an effective treatment for rheumatoid arthritis, given as either two doses of 1000 mg (2 weeks apart) every 6 months (the dose recommended by the US Food and Drug Administration and European Medicines Agency) or two doses of 500 mg (2 weeks apart) or one dose of 1000 mg (a standard low dose) every 6 months. Findings of several small uncontrolled studies suggest that doses lower than the recommended dose or standard low dose might be sufficient for maintenance treatment, potentially improving safety and reducing costs. Therefore, we aimed to compare the efficacy of ultra-low doses of rituximab (one dose of 500 mg or 200 mg) with a standard low dose of rituximab (one dose of 1000 mg) for patients with rheumatoid arthritis who respond to standard doses of rituximab. METHODS: The REDO study is a randomised, double-blind, non-inferiority trial done at five centres in the Netherlands. Adults (aged ≥18 years) with rheumatoid arthritis responding well to rituximab were randomly allocated (1:2:2) to receive intravenous rituximab as one dose of either 1000 mg, 500 mg, or 200 mg, respectively. Volumes of all doses were equal to achieve masking. Randomisation lists were computer-generated and stratified by rheumatoid factor or anti-citrullinated protein antibody status (positive or negative) and concomitant use of conventional synthetic disease modifying antirheumatic drugs (yes or no). The primary analysis was a per-protocol hierarchical testing procedure comparing ultra-low doses with a standard low dose (500 mg vs 1000 mg at 3 months, followed by 500 mg vs 1000 mg at 6 months, 200 mg vs 1000 mg at 3 months, and 200 mg vs 1000 mg at 6 months), using a non-inferiority margin of 0·60 on change from baseline in the 28-joint disease activity score based on C-reactive protein levels (DAS28-CRP). The study is registered at www.trialregister.nl, NTR6117. FINDINGS: Between Dec 15, 2016, and Sept 20, 2018, 142 patients were randomly allocated to either 1000 mg rituximab (n=29), 500 mg rituximab (n=58), or 200 mg rituximab (n=55). The 500 mg dose was non-inferior to 1000 mg at 3 months (mean change from baseline in DAS28-CRP, -0·07, 95% CI -0·41 to 0·27) but not at 6 months (0·29, -0·08 to 0·65). Because of the hierarchical testing procedure, non-inferiority could not be tested for the 200 mg dose. 13 patients had serious adverse events, three (10%) in the 1000 mg group, six (10%) in the 500 mg group, and four (7%) in the 200 mg group. The most frequently reported serious adverse events were cardiovascular. No deaths occurred during the study. A significantly lower incidence of infections was seen in the ultra-low-dose groups compared with the standard dose group (1·10 infections per patient-year with the 1000 mg dose vs 0·52 per patient-year with the 500 mg dose and 0·51 per patient-year with the 200 mg dose; rate ratio 0·47, 95% CI 0·21-0·83; p=0·013 for 500 mg vs 1000 mg; 0·44, 0·22-0·88; p=0·019 for 200 mg vs 1000 mg). INTERPRETATION: Our study did not show non-inferiority of ultra-low doses of rituximab for continued treatment of patients with rheumatoid arthritis. Nonetheless, in clinical practice, a strategy with an ultra-low dose of rituximab might be considered after evaluation of risks and benefits, although further studies are needed to establish non-inferiority. Further analyses and a 2-year observational extension are ongoing and should provide further insight into efficacy and safety. FUNDING: Menzis and Centraal Ziekenfonds.

Preliminary effects of a regional approached multidisciplinary educational program on healthcare utilization in patients with hip or knee osteoarthritis: an observational study.

BACKGROUND: Providing relevant information on disease and self-management helps patients to seek timely contact with care providers and become actively involved in their own care process. Therefore, health professionals from primary care, multiple hospitals and health organisations jointly decided to develop an educational program on osteoarthritis (OA). The objective of the present study was to determine preliminary effects of this OA educational program on healthcare utilization and clinical outcomes. METHODS: We developed an educational group-based program consisting of 2 meetings of 1.5 h, provided by a physiotherapist, a general practitioner (GP) and orthopaedic surgeon or specialized nurse. The program included education on OA, (expectations regarding) treatment options and self-management. Patients were recruited through searching the GPs' electronic patients records and advertisements in local newspapers. At baseline and at 3 months follow-up participating OA patients completed questionnaires. Paired-sample t-tests, McNemar's test and Wilcoxon Signed-Rank test were used to estimate the preliminary effects of the program. RESULTS: A total of 146 participants in 3 districts attended the sessions, of whom 143 agreed to participate in this study; mean age 69.1 years (SD10.2).107 (75%) participants completed both baseline and follow up assessments. The proportion of participants who had visited their GP in the 3 months after the program was lower than 3 months previous to the program (40% versus 25%, p-value 0.01). Also, we observed a decrease in proportion of patients who visited the physio- and exercise therapist, (36.1% versus 25.0%, p-value 0.02). Both illness perceptions and knowledge on OA and treatment options changed positively (Δ-1.8, 95%CI:0.4-3.4, and Δ2.4, 95%CI:-3.0 - -1.6 respectively). No changes in BMI, pain, functioning and self-efficacy were found. However, a trend towards an increase in physical activity was observed. CONCLUSIONS: Our results show that a multidisciplinary educational program may result in a decrease in healthcare utilization and has a positive effect on illness perceptions and knowledge on OA due to clear and consistent information on OA and it treatment options. TRIAL REGISTRATION: Netherlands Trial Register ( NTR5472 ). Registered 22 September 2015.

Treatment Beliefs Underlying Intended Treatment Choices in Knee and Hip Osteoarthritis.

PURPOSE: Patients' beliefs about treatment modalities for knee and hip osteoarthritis (OA) will underlie their treatment choices. Based on the Theory of Planned Behavior, it is hypothesized that patients' beliefs, subjective norm, and perceived behavioral control guide their treatment choices. Also, symptom severity and one's inherent tendency to approach or avoid situations are assumed to play a role. The objective of this study was to test whether these variables were associated with intended treatment choices in knee and hip OA. METHODS: Patients with knee and hip OA were randomly selected from hospital patient records. They completed the Treatment beliefs in OsteoArthritis questionnaire to assess positive and negative treatment beliefs regarding five treatment modalities: physical activities, pain medication, physiotherapy, injections, and arthroplasty. Other measures were intention, subjective norm, perceived behavioral control (ASES), symptom severity (WOMAC), and the person's general tendency to approach or avoid situations (RR/BIS scales). Three models were tested using path analyses to examine the hypothesized associations. RESULTS: Participants were 289 patients. Positive treatment beliefs and subjective norm were consistently associated with intended treatment choice across all treatment modalities. Negative treatment beliefs were associated with intended treatment choices for pain medication and arthroplasty. Other associations were not significant. CONCLUSIONS: This is the first study testing the Theory of Planned Behavior in the context of treatment choices in OA. Findings suggest that foremost positive beliefs about treatment modalities and the norms of one's social environment guide a specific treatment choice. Unexpectedly, symptom severity was not related to intended treatment choices.

Subjective Complaints as the Main Reason for Biosimilar Discontinuation After Open-Label Transition From Reference Infliximab to Biosimilar Infliximab.

OBJECTIVE: To evaluate drug survival, effectiveness, pharmacokinetics, immunogenicity, and safety in daily practice after transitioning treatment from original reference infliximab (Remicade [REM]) to a biosimilar infliximab (CT-P13 [Remsima; Inflectra]) in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. METHODS: Of the initial 222 REM-treated patients, 192 agreed to transition to CT-P13 and were included in this multicenter prospective cohort study. Changes in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and changes in the CRP levels, infliximab trough levels, and anti-infliximab antibody levels were assessed after 6 months, and adverse events (AEs) were documented. Drug survival and prognostic factors were analyzed using Kaplan-Meier and Cox regression analyses. RESULTS: During 6 months follow-up, 24% of the patients (n = 47) discontinued CT-P13. Thirty-seven patients restarted REM, 7 switched to another biologic drug, and 3 continued without a biologic drug. The DAS28-CRP remained stable from baseline to month 6, with a mean ± SD score of 2.2 ± 0.9 at baseline to 2.2 ± 0.8 at 6 months (difference of 0.0 [95% confidence interval (95% CI) -0.1, 0.2]). The BASDAI increased from a mean ± SD of 3.8 ± 2.0 at baseline to 4.3 ± 2.1 at 6 months (difference of +0.5 [95% CI 0.1, 0.9]). The CRP levels, infliximab trough levels, and anti-infliximab antibody levels did not change. Just prior to CT-P13 discontinuation, the DAS28-CRP components tender joint count and patient's global assessment of disease activity, as well as the BASDAI were increased compared to baseline. The most frequently reported AEs were arthralgia, fatigue, pruritus, and myalgia. A shorter REM infusion interval (hazard ratio: 0.77 [95% CI 0.62, 0.95]) at baseline was predictive of discontinuing CT-P13. CONCLUSION: In our cohort, one-fourth of patients discontinued CT-P13 during 6 months of follow-up, mainly due to an increase in the subjective features of the tender joint count and the patient's global assessment of disease activity and/or subjective AEs, possibly explained by nocebo effects and/or incorrect causal attribution effects.

Barriers Impeding the Use of Non-pharmacological, Non-surgical Care in Hip and Knee Osteoarthritis: The Views of General Practitioners, Physical Therapists, and Medical Specialists.

BACKGROUND: Non-pharmacological, non-surgical treatment modalities are underused in the management of knee and hip osteoarthritis (OA). One possible explanation for this could be healthcare providers' opinions about these treatment modalities. The objective of this qualitative study was to identify healthcare providers' views on non-pharmacological, non-surgical care for OA. METHODS: Semi-structured in-depth interviews with 24 healthcare providers (rheumatologists, orthopedic surgeons, physical therapists and general practitioners) were held. Interviews were transcribed verbatim and analyzed using a three-step thematic approach. Two independent researchers continuously reflected upon, compared, discussed, and adjusted the codings. RESULTS: Eight themes were identified reflecting three main barriers to the provision of non-pharmacological, non-surgical care: perceived lack of expertise of the healthcare provider (including a lack of knowledge and skills that are required to support patients), perceived lack of evidence-based treatment (regarding weight management, and the intensity and dosage of physical exercise), and suboptimal organization of care (including hampered dialogue between disciplines and lack of clarity about the roles and responsibilities of disciplines). CONCLUSIONS: Healthcare providers report multiple barriers impeding non-pharmacological, non-surgical care for patients with knee and hip OA. To overcome these barriers, education focused on initiating and supporting lifestyle changes, promotion of interventions according to evidence-based recommendations, and improved organization of care are proposed.

Development of the "Treatment beliefs in knee and hip OsteoArthritis (TOA)" questionnaire.

BACKGROUND: Use of conservative treatment modalities in osteoarthritis (OA) is suboptimal, which appears to be partly due to patients' beliefs about treatments. The aim of this study was to develop a research instrument assessing patients' beliefs about various treatment modalities of hip and knee OA: the 'Treatment beliefs in OA (TOA) questionnaire'. METHODS: The item pool that was retrieved from interviews with patients and healthcare providers comprised beliefs regarding five treatment modalities: physical activity, pain medication, physiotherapy, injections and arthroplasty. After an extensive selection procedure, a draft questionnaire with 200 items was constructed. Descriptive analyses and exploratory factor analyses with oblique rotation were conducted for each treatment modality separately to decide upon the final questionnaire. Internal consistency and test-retest reliability were determined. RESULTS: The final questionnaire comprised 60 items. It was completed by 351 patients with knee or hip OA. Each of the five treatment modalities yielded a two factor solution with 37% to 51% explained variance and high face validity. Factor I included 'positive treatment beliefs' and factor II 'negative treatment beliefs'. Internal consistency (Cronbach α's from 0.72 to 0.87) and test-retest reliability (i.e. intraclass correlation coefficient from 0.66-0.88; standard error of measurement from 0.06-0.11) were satisfactory to good. CONCLUSIONS: The TOA questionnaire is the first questionnaire assessing positive and negative treatment beliefs regarding five treatment modalities for knee and hip OA. The instrument will help to understand whether and to what extent treatment beliefs influence treatment choices.

Does non-adherence to DMARDs influence hospital-related healthcare costs for early arthritis in the first year of treatment?

INTRODUCTION: Non-adherence to disease-modifying antirheumatic drugs (DMARDs) is suspected to relate to health care costs. In this study we investigated this relation in the first year of treatment. METHODS: In a multi-center cohort study with a one year follow up, non-adherence was continuously measured using electronic monitored medication jars. Non-adherence was defined as the number of days with a negative difference between expected and observed opening of the container. Cost measurement focused on hospital costs in the first year: consultations, emergency room visits, hospitalization, medical procedures, imaging modalities, medication costs, and laboratory tests. Cost volumes were registered from patient medical files. We applied multivariate regression analyses for the association between non-adherence and costs, and other variables (age, sex, center, baseline disease activity, diagnosis, socioeconomic status, anxiety and depression) and costs. RESULTS: Of the 275 invited patients, 206 were willing to participate. 74.2% had rheumatoid arthritis, 20.9% had psoriatic arthritis and 4.9% undifferentiated arthritis. 23.7% of the patients were more than 20% non-adherent over the follow-up period. Mean costs are € 2117.25 (SD € 3020.32). Non-adherence was positively related to costs in addition to baseline anxiety. CONCLUSION: Non-adherence is associated with health care costs in the first year of treatment for arthritis. This suggests that improving adherence is not only associated with better outcome, but also with savings.

Psychosocial predictors of DMARD adherence in the first three months of treatment for early arthritis.

OBJECTIVES: To induce disease remission, early arthritis patients should adhere to their disease-modifying antirheumatic drugs (DMARD) in the first months after diagnosis. It remains unknown why some patients are non-adherent. We aimed to identify patients at risk for non-adherence in the first 3 months of treatment. METHODS: Adult DMARD-naive early arthritis patients starting synthetic DMARDs filled out items on potential adherence predictors at baseline. Adherence was measured continuously. Non-adherence was defined as not opening the electronically monitored pill bottle when it should have been. Items were reduced and clustered using principal component analysis. The most discriminating items were identified with latent trait models. We used a multivariable logistic regression model to find non-adherence predictors. RESULTS: 301 patients agreed to participate. Adherence was high and declined over time. Principal component analysis led to 7 dimensions, while subsequent latent trait models analyses led to 15 dimensions. Two dimensions were associated with adherence, one dimension was associated with non-adherence. CONCLUSIONS: Information seeking behavior and positive expectations about the course of the disease are associated with adherence. Patients who become passive because of pain are at risk for non-adherence. PRACTICE IMPLICATIONS: Rheumatologists have cues to identify non-adherence, and may intervene on non-adherence through implementing shared decision making techniques.

Hierarchical structure and importance of patients' reasons for treatment choices in knee and hip osteoarthritis: a concept mapping study.

OBJECTIVES: To improve patients' use of conservative treatment options of hip and knee OA, in-depth understanding of reasons underlying patients' treatment choices is required. The current study adopted a concept mapping method to thematically structure and prioritize reasons for treatment choice in knee and hip OA from a patients' perspective. METHODS: Multiple reasons for treatment choices were previously identified using in-depth interviews. In consensus meetings, experts derived 51 representative reasons from the interviews. Thirty-six patients individually sorted the 51 reasons in two card-sorting tasks: one based on content similarity, and one based on importance of reasons. The individual sortings of the first card-sorting task provided input for a hierarchical cluster analysis (squared Euclidian distances, Ward's method). The importance of the reasons and clusters were examined using descriptive statistics. RESULTS: The hierarchical structure of reasons for treatment choices showed a core distinction between two categories of clusters: barriers [subdivided into context (e.g. the healthcare system) and disadvantages] and outcome (subdivided into treatment and personal life). At the lowest level, 15 clusters were identified of which the clusters Physical functioning, Risks and Prosthesis were considered most important when making a treatment decision for hip or knee OA. CONCLUSION: Patients' treatment choices in knee and hip OA are guided by contextual barriers, disadvantages of the treatment, outcomes of the treatment and consequences for personal life. The structured overview of reasons can be used to support shared decision-making.

Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial.

BACKGROUND: For patients with newly diagnosed rheumatoid arthritis, treatment aim is early, rapid, and sustained remission. We compared the efficacy and safety of strategies initiating the interleukin-6 receptor-blocking monoclonal antibody tocilizumab with or without methotrexate (a conventional synthetic disease-modifying antirheumatic drug [DMARD]), versus initiation of methotrexate monotherapy in line with international guidelines. METHODS: We did a 2-year, multicentre, randomised, double-blind, double-dummy, strategy study at 21 rheumatology outpatient departments in the Netherlands. We included patients who had been diagnosed with rheumatoid arthritis within 1 year before inclusion, were DMARD-naive, aged 18 years or older, met current rheumatoid arthritis classification criteria, and had a disease activity score assessing 28 joints (DAS28) of at least 2·6. We randomly assigned patients (1:1:1) to start tocilizumab plus methotrexate (the tocilizumab plus methotrexate arm), or tocilizumab plus placebo-methotrexate (the tocilizumab arm), or methotrexate plus placebo-tocilizumab (the methotrexate arm). Tocilizumab was given at 8 mg/kg intravenously every 4 weeks with a maximum of 800 mg per dose. Methotrexate was started at 10 mg per week orally and increased stepwise every 4 weeks by 5 mg to a maximum of 30 mg per week, until remission or dose-limiting toxicity. We did the randomisation using an interactive web response system. Masking was achieved with placebos that were similar in appearance to the active drug; the study physicians, pharmacists, monitors, and patients remained masked during the study, and all assessments were done by masked assessors. Patients not achieving remission on their initial regimen switched from placebo to active treatments; patients in the tocilizumab plus methotrexate arm switched to standard of care therapy (typically methotrexate combined with a tumour necrosis factor inhibitor). When sustained remission was achieved, methotrexate (and placebo-methotrexate) was tapered and stopped, then tocilizumab (and placebo-tocilizumab) was also tapered and stopped. The primary endpoint was the proportion of patients achieving sustained remission (defined as DAS28 <2·6 with a swollen joint count ≤four, persisting for at least 24 weeks) on the initial regimen and during the entire study duration, compared between groups with a two-sided Cochran-Mantel-Haenszel test. Analysis was based on an intention-to-treat method. This trial was registered at ClinicalTrials.gov, number NCT01034137. FINDINGS: Between Jan 13, 2010, and July 30, 2012, we recruited and assigned 317 eligible patients to treatment (106 to the tocilizumab plus methotrexate arm, 103 to the tocilizumab arm, and 108 to the methotrexate arm). The study was completed by a similar proportion of patients in the three groups (range 72-78%). The most frequent reasons for dropout were adverse events or intercurrent illness: 27 (34%) of dropouts, and insufficient response: 26 (33%) of dropouts. 91 (86%) of 106 patients in the tocilizumab plus methotrexate arm achieved sustained remission on the initial regimen, compared with 86 (84%) of 103 in the tocilizumab arm, and 48 (44%) of 108 in the methotrexate arm (relative risk [RR] 2·00, 95% CI 1·59-2·51 for tocilizumab plus methotrexate vs methotrexate, and 1·86, 1·48-2·32 for tocilizumab vs methotrexate, p<0·0001 for both comparisons). For the entire study, 91 (86%) of 106 patients in the tocilizumab plus methotrexate arm, 91 (88%) of 103 in the tocilizumab arm, and 83 (77%) of 108 in the methotrexate arm achieved sustained remission (RR 1·13, 95% CI 1·00-1·29, p=0·06 for tocilizumab plus methotrexate vs methotrexate, 1·14, 1·01-1·29, p=0·0356 for tocilizumab vs methotrexate, and p=0·59 for tocilizumab plus methotrexate vs tocilizumab). Nasopharyngitis was the most common adverse event in all three treatment groups, occurring in 38 (36%) of 106 patients in the tocilizumab plus methotrexate arm, 40 (39%) of 103 in the tocilizumab arm, and 37 (34%) of 108 in the methotrexate arm. The occurrence of serious adverse events did not differ between the treatment groups (17 [16%] of 106 patients in the tocilizumab plus methotrexate arm vs 19 [18%] of 103 in the tocilizumab arm and 13 [12%] of 108 in the methotrexate arm), and no deaths occurred during the study. INTERPRETATION: For patients with newly diagnosed rheumatoid arthritis, strategies aimed at sustained remission by immediate initiation of tocilizumab with or without methotrexate are more effective, and with a similar safety profile, compared with initiation of methotrexate in line with current standards. FUNDING: Roche Nederland BV.

Cost of illness and illness perceptions in patients with fibromyalgia.

OBJECTIVES: The disease impact and economic burden of fibromyalgia (FM) are high for patients and society at large. Knowing potential determinants of economic costs may help in reducing this burden. Cognitive appraisals (perceptions) of the illness could affect costs. The present study estimated costs of illness in FM and examined the association between these costs and illness perceptions. METHODS: Questionnaire data of FM severity (FIQ), illness perceptions (IPQ-R-FM), productivity losses (SF-HLQ) and health care use were collected in a cohort of patients with FM. Costs were calculated and dichotomised (median split). Univariate and hierarchic logistic regression models examined the unique association of each illness perception with 1) health care costs and 2) costs of productivity losses. Covariates were FM severity, comorbidity and other illness perceptions. RESULTS: 280 patients participated: 95% female, mean age 42 (SD=12) years. Annualised costs of FM per patient were €2944 for health care, and €5731 for productivity losses. In multivariate analyses, a higher disease impact (FIQ) and two of seven illness perceptions (IPQ-R-FM) were associated with high health care costs: 1) high scores on 'cyclical timeline' reflecting a fluctuating, unpredictable course and 2) low scores on 'emotional representations', thus not perceiving a connection between fibromyalgia and emotions. None of the variables was associated with productivity losses. CONCLUSIONS: Our study indicates that perceiving a fluctuating course and low emotional representation, which perhaps reflects somatic fixation, are associated with health care costs in FM. Future studies should examine whether targeting these illness perceptions results in reduction of costs.

Reasons for Treatment Choices in Knee and Hip Osteoarthritis: A Qualitative Study.

OBJECTIVE: Conservative treatment modalities in osteoarthritis (OA) of the hip or knee are underused, whereas the demand for surgery is rising substantially. To improve the use of conservative treatment modalities, a more in-depth understanding of the reasons for patients' treatment choices is required. This study identifies the reasons for choice of treatment in patients with hip or knee OA. METHODS: Semistructured in-depth interviews with 24 OA patients were held. Stratified purposive sampling was used to enrich data variation. Interviews were transcribed verbatim and subsequently coded using a thematic approach. Two independent researchers reflected on, compared, discussed, and adjusted the coding. RESULTS: Various treatment modalities were discussed by respondents: medication, exercise, physical therapy, injections, surgery, complementary, and alternative treatment. Four key themes underlying the choice for or against a treatment modality for OA were identified: 1) treatment characteristics: expectations about its effectiveness and risks, the degree to which it can be personalized to a patient's needs and wishes, and the accessibility of a treatment; 2) personal investment in terms of money and time; 3) personal circumstances: age, body weight, comorbidities, and previous experience with a treatment; and 4) support and advice from the patient's social environment and health care providers. CONCLUSION: The 4 identified key themes enhance the insight of health care providers into the widespread reasons influencing patients' treatment choices for knee or hip OA. This knowledge can be used in clinical practice to aid shared decision making, which may lead to optimized treatment choices for both conservative and surgical treatment.

Non-adherence to disease-modifying antirheumatic drugs is associated with higher disease activity in early arthritis patients in the first year of the disease.

INTRODUCTION: Non-adherence to disease-modifying antirheumatic drugs (DMARDs) hampers the targets of rheumatoid arthritis (RA) treatment, obtaining low disease activity and decreasing radiological progression. This study investigates if, and to what extent, non-adherence to treatment would lead to a higher 28-joint count disease activity score (DAS28) in the first year after diagnosis. METHODS: Adult patients from an ongoing cohort study on treatment adherence were selected if they fulfilled the EULAR/ACR2010 criteria for RA, and were to start with their first DMARDs. Clinical variables were assessed at baseline and every 3 months. Non-adherence was continuously electronically measured and was defined as the proportion of days with a negative difference between expected and observed openings of the medication container out of the 3-month period before DAS28 measurement. Generalized linear mixed models were used to investigate whether the DAS28 related to non-adherence. Covariates included were age, sex, baseline DAS28, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibodies (ACPA) positivity, anxiety, depression, weeks of treatment, number of DMARDs used, education level, use of subcutaneous methotrexate and biological use. RESULTS: One hundred and twenty patients met the inclusion criteria for RA. During the study period 17 patients became lost to follow-up. There was a decline in adherence over time for all DMARDs except for prednisone. Non-adherence is a predictor of disease activity in the first 6 months of therapy, adjusted for weeks of treatment, baseline DAS28, and baseline anxiety. CONCLUSIONS: Non-adherence relates to disease activity. Therefore, interventions towards enhancing adherence can improve disease outcome.

COX-2-selective NSAIDs and risk of hip or knee replacements: a population-based case-control study.

Disease models of osteoarthritis (OA) have shown that COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs, coxibs) may have beneficial effects on cartilage. Clinical or epidemiological evidence for this potential association is scarce. The objective of this study was to evaluate the risk of hip or knee replacement in users of coxibs compared to nonselective NSAIDs. A population-based case-control study was conducted with the Dutch PHARMO Record Linkage System. Cases (n = 26,202) had a first replacement of the hip or knee after enrollment (2000-2009). Up to two controls (without hip or knee replacement) were matched by year of birth, gender, healthcare region, and calendar year. Using conditional logistic regression analysis, odds ratios (ORs) for hip or knee replacement were estimated by comparing long-term (≥1 year) nonselective NSAID use with long-term coxib use. Analyses were statistically adjusted for disease and drug history. Long-term use of nonselective NSAIDs was not associated with a different risk of hip replacement (adjusted OR = 0.89, 95 % CI 0.65-1.22) or knee replacement (adjusted OR = 0.74, 95 % CI 0.49-1.11) as compared to long-term coxib use. Results were not different after stratification by gender, age, and cardiovascular or gastrointestinal disease. This study shows that long-term users of nonselective NSAIDs do not have a different risk of hip or knee replacement as compared to long-term coxib users. Therefore, our results do not support that patients with OA could benefit from using coxibs in order to slow progression of this disease.

['Rheumatoid arthritis' in a Surinamese man: leprosy]. / 'Reumatoïde artritis' bij een Surinaamse man: lepra.

Rheumatoid arthritis was diagnosed in a 65-year-old man from Suriname, on the basis of clinical and radiological findings. However, he was eventually diagnosed with leprosy. This emerged when the patient developed skin lesions and complained of increasing sensibility disorders during treatment for the alleged rheumatoid arthritis. He was treated with a combination therapy consisting of rifampicin, clofazimine, dapsone, and prednisone. The skin lesions and joint symptoms were resolved as a result of this, but the sensibility disorders persisted. As physicians are not sufficiently familiar with leprosy and the condition has many manifestations that can mimic more frequently occurring diseases, leprosy is often diagnosed at a later stage. This may result in irreversible damage, especially to the peripheral nerves, which may lead to disability. Therefore, for patients who originate from areas where leprosy is endemic and who suffer from joint complaints in combination with skin or sensibility disorders, the diagnosis of leprosy should be considered.

Gene transfer of tissue inhibitor of metalloproteinases-3 reverses the inhibitory effects of TNF-alpha on Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts.

Apart from counteracting matrix metalloproteinases, tissue inhibitor of metalloproteinases-3 (TIMP-3) has proapoptotic properties. These features have been attributed to the inhibition of metalloproteinases involved in the shedding of cell surface receptors such as the TNFR. However, little is known about effects of TIMP-3 in cells that are not susceptible to apoptosis by TNF-alpha. In this study, we report that gene transfer of TIMP-3 into human rheumatoid arthritis synovial fibroblasts and MRC-5 human fetal lung fibroblasts facilitates apoptosis and completely reverses the apoptosis-inhibiting effects of TNF-alpha. Although TNF-alpha inhibits Fas/CD95-induced apoptosis in untransfected and mock-transfected cells, fibroblasts ectopically expressing TIMP-3 are sensitized most strongly to Fas/CD95-mediated cell death by TNF-alpha. Neither synthetic MMP inhibitors nor glycosylated bioactive TIMP-3 are able to achieve these effects. Gene transfer of TIMP-3 inhibits the TNF-alpha-induced activation of NF-kappaB in rheumatoid arthritis synovial fibroblasts and reduces the up-regulation of soluble Fas/CD95 by TNF-alpha, but has no effects on the cell surface expression of Fas. Collectively, our data demonstrate that intracellularly produced TIMP-3 not only induces apoptosis, but also modulates the apoptosis-inhibiting effects of TNF-alpha in human rheumatoid arthritis synovial fibroblast-like cells. Thus, our findings may stimulate further studies on the therapeutic potential of gene transfer strategies with TIMP-3.