Retrospective evaluation of continuation rates following a switch to subcutaneous methotrexate in rheumatoid arthritis patients failing to respond to or tolerate oral methotrexate: the MENTOR study.

OBJECTIVES: To retrospectively evaluate continuation rates in patients with rheumatoid arthritis (RA) who failed to respond to or tolerate oral methotrexate (MTX) and were subsequently switched to subcutaneous MTX (SC MTX) in routine clinical practice. METHOD: We conducted a retrospective review of all patients with RA who had been prescribed SC MTX following oral MTX at the Norfolk and Norwich University Hospital and had been captured on the hospital pharmacy database of MTX use between 17 May 2011 and 20 March 2012. Only patients for whom complete records were available before and for at least 6 months after the switch were included. RESULTS: A total of 196 patients were included in the analysis (75.5% women; mean age at diagnosis 47.4 years; mean duration of oral MTX therapy 6.6 years). Patients were changed from oral to SC MTX because of lack of efficacy (50.5%), adverse events (43.9%), or other/unknown reasons (5.6%). High continuation rates were seen, with 83.0% of patients analysed still on SC MTX at 1 year, 75.2% at 2 years, and 47.0% at 5 years. Following the switch to SC MTX, < 10% of patients were prescribed additional biologic therapy during the first and second year because of an insufficient response. CONCLUSIONS: Treatment with SC MTX results in high continuation rates in patients who fail to respond to or tolerate oral MTX. Consequently, management guidelines should be adapted to include advice that SC MTX should be used before biologic therapy and that MTX failure is defined as failure only when use of SC MTX has failed.

'In one ear and out the other - it's a lot to take in': a qualitative study exploring the informational needs of patients with ANCA-associated vasculitis.

OBJECTIVES: To explore the informational needs of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Three focus groups and eight one-to-one interviews were conducted with patients with AAV. A purposeful sample of 15 patients (ten female) [disease: three Churg-Strauss syndrome (CSS); nine granulomatosis with polyangiitis (GPA); one microscopic polyangiitis (MPA); two polyarteritis nodosa (PAN)] participated in the focus groups. Eight (five female) (disease: three CSS; four GPA; one MPA) participated in the one-to-one interviews. A semi-structured interview guide was used to explore patients' experiences of informational needs. The focus groups and interviews were audio-recorded and transcribed verbatim, and analysed using the framework technique. RESULTS: Emergent themes were: reaction to diagnosis, need for information on disease management and access to knowledgeable practitioners. When given the initial diagnosis, all patients described themselves as being too ill to take in information and that they later found it difficult to find information. Most information received at diagnosis was in the form of verbal information given by the hospital doctor. Patients wanted positive but truthful information in the form of a booklet. CONCLUSIONS: Receiving the diagnosis of a rare, potentially life-threatening disease and then dealing with its complex treatment causes anxiety and fear and can impede information retention and recall. Patients want information on diagnosis and treatment but this should be tailored to individual needs, including timing that is appropriate for them. All patients wanted the opportunity to discuss their illness and its management with a knowledgeable healthcare practitioner but also wanted printed forms of information to assimilate at their own pace.

Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials.

OBJECTIVES: Because standard immunosuppressive treatment for antineutrophil cytoplasm antibody-associated vasculitis (AAV) (granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA)) has been associated with a significant risk of developing cancer, the cancer incidence of treated AAV patients was assessed. METHODS: This analysis concerned 535 patients with newly diagnosed AAV from 15 countries who had been enrolled between 1995 and 2002 in four European clinical trials. Over the period 2004-7, study participants' follow-up events were updated, including cancers diagnosed. Age, sex and area-standardised incidence ratios (SIR) and their 95% CI were calculated by linkage to five national cancer databases. RESULTS: During the 2650 person-years' observation period, 50 cancers were diagnosed in 46 patients. SIR (95% CI) were 1.58 (1.17 to 2.08) for cancers at all sites, 1.30 (0.90 to 1.80) for cancers at all sites excluding non-melanoma skin cancer (NMSC), 2.41 (0.66 to 6.17) for bladder cancer, 3.23 (0.39 to 11.65) for leukaemia, 1.11 (0.03 to 6.19) for lymphoma and 2.78 (1.56 to 4.59) for NMSC. Subgroup SIR for cancers at all sites were 1.92 (1.31 to 2.71) for GPA and 1.20 (0.71 to 1.89) for MPA. CONCLUSIONS: Cancer rates for AAV patients treated with conventional immunosuppressive therapy exceeded those expected for the general population. This cancer excess was largely driven by an increased incidence of NMSC. The smaller cancer risk magnitude in this cohort, compared with previous studies, might reflect less extensive use of cyclophosphamide in current treatment protocols. Longer follow-up data are warranted to appraise the risk of developing cancers later during the course of AAV.

Autoimmune disease as a risk factor for globus pharyngeus: a cross-sectional epidemiological study.

OBJECTIVE: To assess the prevalence and severity of globus-type symptoms in individuals who have a prior diagnosis of autoimmune disease. DESIGN: Cross-sectional questionnaire. PARTICIPANTS AND SETTING: One hundred and nine patients with autoimmune disease (rheumatoid arthritis, seronegative spondarthritis, connective tissue disease, systemic vasculitis) and 41 patients with non-autoimmune disease (osteoarthritis/osteoporosis) attending a rheumatology tertiary referral clinic at Norfolk & Norwich University Hospitals NHS Foundation Trust. The results from this study were compared to previous published figures in patients with globus pharyngeus (n = 105) and normal population (n = 174). MAIN OUTCOME MEASURES: Glasgow Edinburgh Throat Scale questionnaire; Reflux Symptom Index; Anxiety/Depression Scale. RESULTS: Patients with autoimmune disease demonstrate a significantly higher prevalence for 5/10 symptoms on the Glasgow Edinburgh Throat scale score when compared to the non-autoimmune control group (P ≤ 0.01). This significant difference increases to 9/10 symptoms when compared to published results for the normal population (P = 0.01). No significant difference was found when comparing the autoimmune and non-autoimmune control group reflux symptom index (P = 0.64) or anxiety depression scale (P = 0.71). CONCLUSION: Patients with autoimmune disease have a significantly increased prevalence of globus symptoms when compared to the healthy population. A further prospective study is required to decipher the effect of pharmacotherapy as a possible causative factor.

EULAR recommendations for the management of large vessel vasculitis.

OBJECTIVES: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. METHODS: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. RESULTS: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. CONCLUSIONS: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.

EULAR recommendations for the management of primary small and medium vessel vasculitis.

OBJECTIVES: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. METHODS: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. RESULTS: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. CONCLUSIONS: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.

Exploring the healthcare journey of patients with rheumatoid arthritis: a mapping project - implications for practice.

OBJECTIVE: Consumers of healthcare can reveal important insights into the personal challenges they experience when negotiating their health needs. The National Rheumatoid Arthritis Society (NRAS) wanted to explore the experiences of those with rheumatoid arthritis (RA) in order to understand the impact on the individual and on healthcare resources and benchmark care against published standards and guidelines. METHODS: A project was designed to explore the experiences of individuals with sero-positive RA who had been diagnosed for three years or less. Qualitative semi-structured interviews were used and combined with process mapping to explore the experiences of a purposeful sample of individuals with RA. The information generated was mapped and variances explored. Ethical approval was not required as the data were collected outside the National Health Service. RESULTS: Twenty-two participants' stories were mapped. Fifty per cent of participants sought a medical opinion within three weeks of symptom onset and the majority received a disease-modifying anti-rheumatic drug within six months from first presenting symptoms. Work-related issues were highlighted by 13 participants, and seven of these experienced job losses directly attributed to their diagnosis. CONCLUSIONS: This unique mapping approach used qualitative research and process mapping to compare patient experiences against recognized standards and guidelines. These twenty-two stories reveal important insights into the challenges experienced in negotiating these healthcare journeys and the impact upon the individual as a result of variances in standards of care received. The participants in this study were chiefly self-motivated, informed and articulate, and did not reflect the broad ethnic, social or cultural diversity in the UK. Limitations must also be considered in relation to perceptions and recall of participants over a three-year period, as these may have altered over time and illness experience.

A comparative study of the diagnostic accuracy of ELISA systems for the detection of anti-neutrophil cytoplasm antibodies available in Japan and Europe.

OBJECTIVES: Primary systemic vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA) differs in its frequency and clinical expression between Japan and Europe. We sought to ascertain whether such differences arise from the performance of enzyme-linked immunosorbent assays (ELISAs) for ANCA. METHODS: Plasma samples from 64 consecutive Japanese patients with a clinical and histological diagnosis of primary systemic vasculitis including microscopic polyangiitis (MPA; n=52), Churg-Strauss syndrome (CSS; n=1), and Wegener's granulomatosis (WG; n=11), or those from disease controls with non-vasculitic glomerulonephritis (n=54) and healthy controls (n=55) were tested for the presence of myeloperoxidase (MPO) by ELISAs available in Japan (Nipro and MBL) and compared with those in Europe (Wieslab). The sensitivity and specificity were calculated for each ELISA, and its diagnostic performance was assessed by receiver operating characteristic curve analysis. RESULTS: The sensitivity and specificity of either MPO-ANCA assays for a diagnosis of MPA were 90.4% and 98.2% (Nipro), 88.2% and 96.3% (MBL), and 86.5% and 99.1% (Wieslab). The overall diagnostic performance, assessed as the area under curve of the MPO-ANCA ELISAs for MPA were 0.946+/-0.022 (Nipro), 0.970+/-0.017 (MBL), and 0.971+/-0.017 (Wieslab), while that of PR3-ANCA ELISAs for WG were 0.986+/-0.025 (Nipro), 0.993+/-0.017 (MBL), and 0.916+/-0.059 (Wieslab). CONCLUSIONS: The MPO-ANCA ELISAs commercially available in Japan exhibited high sensitivity and specificity for the diagnosis of ANCA-associated vasculitides and provided similar diagnostic value to those in Europe. These results facilitate further international comparison of ANCA-associated vasculitides between Japanese and European populations.

Five-year outcome of a primary-care-based inception cohort of patients with inflammatory polyarthritis plus psoriasis.

OBJECTIVES: To establish whether patients with inflammatory arthritis plus psoriasis have a different outcome from those who do not have psoriasis. METHODS: Seventy-nine patients with inflammatory arthritis plus psoriasis were recruited by the Norfolk Arthritis Register (NOAR) in 1990-94 and followed for 5 yrs. Their outcome was compared with the remainder (n = 755) of the NOAR cohort. We then restricted the analysis to subjects who were rheumatoid factor (RF)-negative, and compared those with and without psoriasis. Outcomes studied included remission, deformed joint count, the presence and extent of erosive damage and physical function. RESULTS: Patients with psoriasis were younger, more likely to be male, less likely to be RF-positive and more likely to have been treated with disease-modifying drugs than patients without psoriasis. After adjustment for age, gender and treatment, the only differences between the psoriasis and non-psoriasis groups were in RF positivity (adjusted odds ratio 0.44; 95% CI 0.25, 0.78) and in the Larsen score in patients with erosions. CONCLUSIONS: Patients with inflammatory arthritis plus psoriasis have a similar outcome to other RF-negative patients with arthritis.

Rituximab therapy in patients with resistant rheumatoid arthritis: real-life experience.

OBJECTIVES: Rituximab has recently been shown to be effective in suppressing disease activity in patients with rheumatoid arthritis (RA) who fail anti-TNF therapy. We present our experience of treating patients with long-standing, multi-DMARD and anti-TNF resistant RA with rituximab in 'real-life' setting. METHODS: Patients with RA resistant to more than two anti-TNF drugs and with persistent disease activity (DAS28 > 5.1) were considered for treatment with rituximab (two infusions 1000 mg each, a fortnight apart). DAS28 and HAQ scores were performed at baseline, 3 and 6 months post-treatment. Response to rituximab was defined as per the EULAR response criteria. Re-treatment with a second cycle of rituximab was offered if they had responded to the earlier one but flared. RESULTS: Twenty patients received rituximab. Median disease duration was 16 yrs (range 5-39) and 90% were rheumatoid factor positive. Median number of biologics received pre-treatment was two (range 2-4). Rituximab treatment led to a significant reduction in DAS28 score (P < 0.0001) at 3 months and various other disease parameters. The benefit was sustained at 6 months. Moderate-to-good EULAR response was seen in 85% of patients at 3 months and 60% at 6 months. No significant side effects were observed. 50% of the patients flared and received re-treatment. Interval to re-treatment varied from 6 to 18 months. The majority of the RA patients responded to re-treatment with rituximab and no major side effects were observed. CONCLUSION: Rituximab was effective in controlling disease activity in anti-TNF therapy resistant RA patients in 'real-life' setting. Rituximab was safe with no major side effects. Re-treatment with rituximab was safe and efficacy was maintained.

Low-dose infliximab treatment for ankylosing spondylitis--clinically- and cost-effective.

OBJECTIVES: Infliximab has been shown to be effective in the treatment of ankylosing spondylitis (AS) when treated in a dose of 5 mg/kg at 6 weekly intervals. This dose of infliximab has not been determined by any structured randomized trials and has significant cost implications. We describe our experience of treating AS with low-dose infliximab (3mg/kg at 8 weekly intervals). The efficacy and cost implications are discussed. METHODS: Patients who had active AS [Bath AS Disease Activity Index (BASDAI) > or = 4] were treated with infliximab 3 mg/kg at 0, 2, 6 weeks and thereafter at 8 weekly intervals. Response to treatment was defined as 50% improvement in BASDAI. Other response criteria such as ASAS 20, 40 and five of the six criteria were also assessed. Direct drug costs for infliximab were determined. RESULTS: Twenty-two consecutive AS patients received infliximab. All 22 completed treatment for 3 months, 15 patients for 6 months and 14 for 12 months. Mean age was 45 years (range 21-62) and mean disease duration 14.5 years (range 2-43). Of the patients, 54% achieved a 50% BASDAI response at 3 months and the benefit was sustained at 12 months in 63%. Similar response rate was seen with the other assessment criteria. Direct drug costs were significantly lower when low-dose infliximab regimen was used. CONCLUSIONS: Low-dose infliximab (3 mg/kg at 8 weekly infusions) is effective in the treatment of AS. Higher doses are required in a small proportion of patients when treatment is only partially effective. Titrating the dose and frequency of infusions may be required in individual patients to achieve optimal response. Using low-dose infliximab has significant economic implications.

Coping and psychological adjustment in recent-onset inflammatory polyarthritis: the role of gender and age.

OBJECTIVES: To examine the role of gender, age and coping in psychological adjustment of patients with early inflammatory polyarthritis (IP). METHODS: One hundred and twelve patients with IP of up to 18 months' duration from the Norfolk Arthritis Register completed questionnaires measuring coping, anxiety, disability and pain. RESULTS: Thirty-six per cent of the patients were at risk of depressive symptoms. Women had significantly higher levels of depression and anxiety than men. Regression analyses showed that pain and (low) illness acceptance predicted levels of depression. Younger age, wishful thinking and covering up predicted anxiety levels. CONCLUSIONS: The study found higher levels of depression and anxiety for women than men with early IP. Psychological distress was predicted by younger age, specific coping strategies and high levels of pain.

Methotrexate-induced pancytopenia: serious and under-reported? Our experience of 25 cases in 5 years.

OBJECTIVE: To ascertain the extent of methotrexate (MTX)-related pancytopenia at the Norfolk and Norwich University Hospital (NNUH) between 1999 and 2004. METHODS: Patients were identified by a department database search, review of pharmacy records and personal communication. Pancytopenia was defined as white blood cell count (WBC) <3.5 x 10(9)/l, haemoglobin (Hb) <11 g/dl and platelet count <130 x 10(9)/l. Severe pancytopenia was defined as WBC <2.0 x 10(9)/l, Hb <10 g/dl and platelet count <50 x 10(9)/l. RESULTS: Twenty-five patients had MTX-induced pancytopenia. Eleven patients were taking folic acid and one folinic acid. The median dose of MTX was 12.5 mg weekly (interquartile range 5.625 mg) and median duration of treatment 36 months (interquartile range 40.5 months). The severity of pancytopenia correlated with the dose (P = 0.04). The numbers of patients with potential risk factors were: renal insufficiency, 8; pre-existing folate deficiency, 7; age >75 yr, 15; hypoalbuminaemia, 18; pre-existing infection with hip prosthesis, 1; possible drug interactions, 18; dosing errors, 1; and polypharmacy, 15. Pancytopenia was detected by routine blood monitoring in nine patients. There were seven deaths (28% mortality), five from sepsis and two from acute myeloid leukaemia. CONCLUSION: This is the largest reported individual case series of MTX-induced pancytopenia. With the increasing long-term use of MTX, it is important that patients be monitored for haematological side-effects as pancytopenia can be a late manifestation. Pharmacogenetics may hold the answer to predicting who is at risk of this potentially fatal complication of MTX.