Association of clinic setting with quality indicator performance in systemic lupus erythematosus: a cross-sectional study.

BACKGROUND: Healthcare quality for systemic lupus erythematosus (SLE) is a modifiable target for improving patient outcomes. We aimed to assess the quality of care processes in different clinic settings, comparing a subspecialty lupus clinic with hospital-based and private general rheumatology clinics. METHODS: Patients with SLE (n = 258) were recruited in 2016 from a subspecialty lupus clinic (n = 147), two hospital general rheumatology clinics (n = 56) and two private rheumatology clinics (n = 55). Data were collected from medical records and patient questionnaires. Quality of care was assessed using 31 validated SLE quality indicators (QI) encompassing diagnostic work-up, disease and comorbidity assessments, drug monitoring, preventative care and reproductive health. Per-QI performance was measured as a percentage of patients that met the QI relative to the number of patients eligible. Per-patient QI performance was calculated as a percentage of QIs met relative to the number of eligible QIs for each patient. Per-QI and per-patient QI performance were compared between the three clinic settings, and multiple regression performed to adjust for sociodemographic, disease and healthcare factors. RESULTS: Per-QI performance was generally high across all clinic settings for diagnostic work-up, comorbidity assessment, lupus nephritis, drug monitoring, prednisolone taper, osteoporosis and pregnancy care. Median [IQR] per-patient performance on eligible QIs was higher in the subspeciality lupus clinic (66.7% [57.1-74.1]) than the hospital general rheumatology (52.7% [47.5-58.1]) and private rheumatology (50.0% [42.9-60.9]) clinics (p <0.001) and the difference remained significant after multivariable adjustment. The subspecialty lupus clinic recorded higher per-QI performance for documentation of disease activity, disease damage, cardiovascular risk factor and drug toxicity assessments, pre-immunosuppression hepatitis and tuberculosis screening, new medication counselling, vaccinations, sun avoidance education and contraception counselling. CONCLUSIONS: SLE patients managed in a subspecialty lupus clinic recorded higher per-patient QI performance compared to hospital general rheumatology and private rheumatology clinics, in part related to better documentation on certain QIs.

Reasons for Biologic and Targeted Synthetic Disease-modifying Antirheumatic Drug Cessation and Persistence of Second-line Treatment in a Rheumatoid Arthritis Dataset.

OBJECTIVE: To provide real-world evidence about the reasons why Australian rheumatologists cease biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) when treating patients with rheumatoid arthritis (RA), and to assess (1) the primary failure rate for first-line treatment, and (2) the persistence on second-line treatments in patients who stopped first-line tumor necrosis factor inhibitors (TNFi). METHODS: This is a multicenter retrospective, noninterventional study of patients with RA enrolled in the Australian Optimising Patient outcome in Australian RheumatoLogy (OPAL) dataset with a start date of b/tsDMARD between August 1, 2010, and June 30, 2017. Primary failure was defined as stopping treatment within 6 months of treatment initiation. RESULTS: Data from 7740 patients were analyzed; 6914 patients received first-line b/tsDMARD. First-line treatment was stopped in 3383 (49%) patients; 1263 (37%) were classified as primary failures. The most common reason was "lack of efficacy" (947/2656, 36%). Of the patients who stopped first-line TNFi, 43% (1111/2560) received second-line TNFi, which resulted in the shortest median time to stopping second-line treatment (11 months, 95% CI 9-12) compared with non-TNFi. The longest second-line median treatment duration after first-line TNFi was for patients receiving rituximab (39 months, 95% CI 27-74). CONCLUSION: A large proportion of patients who stopped first-line TNFi therapy received another TNFi despite evidence for longer treatment persistence on second-line b/tsDMARD with a different mode of action. Lack of efficacy was recorded as the most common reason for making a switch in first-line treatment of patients with RA.

Treatment patterns among patients with rheumatic disease (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated arthritis (UnA)) treated with subcutaneous TNF inhibitors.

The aim was to describe the real-world treatment persistence of subcutaneous TNF inhibitors (TNFi) for patients with inflammatory rheumatic disease newly initiating treatment with biologic disease-modifying antirheumatic drugs (bDMARD). This was a retrospective cohort study that extracted data for new users of TNFi between 1 August 2010 and 31 August 2016 from the Australian Optimising Patient outcome in Australian RheumatoLogy (OPAL) registry. Patients were 1:1 propensity-score matched with golimumab based on their age, sex, year of index, C-reactive protein level, baseline treatment combination and disease. Treatment persistence was calculated. Data from 3749 patients were extracted (adalimumab n = 1518; certolizumab n = 298; etanercept n = 1068; golimumab n = 865). The mean (SD) ages of patients were 51.7 (14.2) years for adalimumab, 53.7 (14.0) years for certolizumab, 52.8 (14.3) years for etanercept and 52.3 (14.6) years for golimumab, with disease durations 7.7 (10.5), 8.8 (9.2), 8.1 (10.4) and 7.3 (9.7) years, respectively. Two thirds of the patients were women. There was no significant difference in treatment persistence by treatment in the overall population (adalimumab 33.6 [95% CI 28.6-40.7], certolizumab 24.8 [95% CI 21.3-42.1], etanercept 27.6 [95% CI 23.4-36.5], golimumab 30.3 [95% CI 23.26-36.5]; months, p = 0.545), or in the propensity score-matched population. No safety signals were detected. In this real-world biologic-naïve Australian inflammatory rheumatic disease cohort treated with subcutaneous TNF inhibitors during the period 2010-2016, there was no difference in treatment persistence between agents.

A retrospective review of the persistence on bDMARDs prescribed for the treatment of rheumatoid arthritis in the Australian population.

AIM: To describe the persistence of biologic disease modifying anti-rheumatic drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the influence of methotrexate and other conventional DMARD (cDMARD) concomitant medications, and treatment line on bDMARD persistence and glucocorticoids usage. METHOD: RA patients, from the 10% Australian Medicare random sample, aged ≥18 for whom bDMARDs were dispensed were included. Individual sub-cutaneous (SC) anti-tumor necrosis factor-α (anti-TNFα) agents were combined as they were equivalent. RESULTS: Data from 1230 patients were analyzed. For all patients the 12-month persistence rates (based on Kaplan-Meier estimates) were 76% for intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC-anti-TNFs and 36% IV-infliximab. Persistence rates on first-line bDMARDs were 79% (tocilizumab and abatacept), 64% (SC-anti-TNFs) and 13% (infliximab); rates were sustained for tocilizumab but dropped to 49% for abatacept and 51% for SC-anti-TNFs in the second-line setting. Median treatment persistence was 40 months tocilizumab (95% CI: 30-ND), 33 months abatacept (95% CI: 20-ND); 22 months SC-anti-TNF (95% Cl: 18-27), and 4 months infliximab (95% CI: 2-13). Longer persistence was observed for SC-anti-TNFs and abatacept combined with methotrexate or other cDMARDs. For tocilizumab, persistence was robust with or without concomitant medications. The median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0 mg/day (min 0, max 17.3) over 2 years. CONCLUSIONS: Treatment persistence was longer on tocilizumab followed by abatacept then SC-anti-TNF therapy and was influenced by co-therapy. Glucocorticoid dosage decreased with bDMARD use. This real-world data highlights that persistence on bDMARDs differs according to biologics mode of action and co-therapy.

Psoriatic arthritis treatment regimens, therapy duration and reasons for cessation in the biologics era: a multi-centre Australian study.

AIM: To describe the treatment regimens, duration of therapy and reasons for disease-modifying antirheumatic drug (DMARD) cessation in a large psoriatic arthritis (PsA) cohort. METHODS: A retrospective non-interventional multi-centre study using Audit4 electronic medical records, with de-identified, routinely collected clinical data from rheumatology practices in the OPAL consortium (Optimising Patient outcomes in Australian rheumatoLogy) during November 2015. Baseline characteristics, type and duration of conventional and biologic DMARDs (cDMARD and bDMARD, respectively), disease activity (Disease Activity Score of 28 joints C-reactive protein [DAS28-CRP]), and reasons for treatment cessation were recorded. RESULTS: A total of 3422 rheumatologist-diagnosed PsA patients were included: 60% female, mean age 54 years and disease duration 10 years. Of patients with treatment recorded (n = 2948), 46% were on cDMARD monotherapy, 19% bDMARD monotherapy, 13% combination bDMARD and cDMARDs, 11% combination cDMARDs and 10% no DMARDs. Of those with DAS28-CRP results (n = 494), the highest mean DAS28-CRP was 3.32 on combination cDMARDs, and the lowest was 2.19 on bDMARD monotherapy. Median duration on cDMARD monotherapy was 33.5 months (n = 2232), on bDMARD monotherapy 110.1 months (n = 751), on combination bDMARD and cDMARDs 68.5 months (n = 559). The most common reasons for cessation of cDMARD monotherapy was adverse reactions (41%), for bDMARD monotherapy lack of efficacy (26%), and for combination bDMARD and cDMARDs treatment completed or no longer required (37%). CONCLUSION: Most PsA patients were prescribed DMARD therapies with a large proportion receiving cDMARDs. Patients on combination cDMARD therapies had the highest DAS28-CRP results. Adverse reactions were the most common reason for cessation of cDMARD monotherapy, whereas for bDMARD monotherapy it was lack of efficacy.

Australian and New Zealand recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion in the 3e Initiative.

AIM: To develop evidence-based recommendations for the diagnosis and management of gout in Australia and New Zealand as part of the multi-national 3e Initiative. METHOD: Using a formal voting process, a panel of 78 international rheumatologists selected 10 key clinical questions pertinent to the diagnosis and management of gout. An additional question was also developed by participating Australian and New Zealand rheumatologists. Each question was investigated with a systematic literature review. MEDLINE, EMBASE, Cochrane CENTRAL and abstracts from 2010 to 2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, 47 Australian and New Zealand rheumatologists developed national recommendations. For each recommendation the level of agreement was assessed and the level of evidence graded. RESULT: Eleven recommendations were produced relating to the diagnosis of gout, different aspects of the management of gout, cardiovascular and renal comorbidities and the management of asymptomatic hyperuricemia. The mean level of agreement with the recommendations was 9.1 on a 1-10 scale, with 10 representing full agreement. CONCLUSION: Eleven Australian and New Zealand recommendations on the diagnosis and management of gout were developed combining systematically reviewed evidence with local expertise, enhancing their utility in clinical practice.

Is there still a role for abatacept in the treatment of lupus?

INTRODUCTION: The quest for safer and more effective treatments for systemic lupus erythematosus (SLE) has led to the development of many new biologic therapies. Abatacept is the first drug targeting co-stimulation between T cells and antigen presenting cells, with abundant pre-clinical evidence to support its use in SLE. AREAS COVERED: This review will present the relevant aspects of lupus pathophysiology pertaining to the mechanism of action of abatacept, a summary of murine studies and the latest human clinical trials. EXPERT OPINION: Abatacept has demonstrated efficacy in both rheumatoid arthritis and psoriatic arthritis, and earlier studies have suggested tantalising evidence of efficacy in SLE. However, the latest randomised double-blinded study showed disappointingly negative results, much like the case of rituximab in SLE. Currently, abatacept remains a possible therapeutic option as an off-label therapy, and it is a part of our therapeutic armamentarium in difficult cases. The need to find appropriate definitions of response and optimal study design continues to be paramount in the field of lupus therapies.

Acupuncture for treating fibromyalgia.

BACKGROUND: One in five fibromyalgia sufferers use acupuncture treatment within two years of diagnosis. OBJECTIVES: To examine the benefits and safety of acupuncture treatment for fibromyalgia. SEARCH METHODS: We searched CENTRAL, PubMed, EMBASE, CINAHL, National Research Register, HSR Project and Current Contents, as well as the Chinese databases VIP and Wangfang to January 2012 with no language restrictions. SELECTION CRITERIA: Randomised and quasi-randomised studies evaluating any type of invasive acupuncture for fibromyalgia diagnosed according to the American College of Rheumatology (ACR) criteria, and reporting any main outcome: pain, physical function, fatigue, sleep, total well-being, stiffness and adverse events. DATA COLLECTION AND ANALYSIS: Two author pairs selected trials, extracted data and assessed risk of bias. Treatment effects were reported as standardised mean differences (SMD) and 95% confidence intervals (CI) for continuous outcomes using different measurement tools (pain, physical function, fatigue, sleep, total well-being and stiffness) and risk ratio (RR) and 95% CI for dichotomous outcomes (adverse events). We pooled data using the random-effects model. MAIN RESULTS: Nine trials (395 participants) were included. All studies except one were at low risk of selection bias; five were at risk of selective reporting bias (favouring either treatment group); two were subject to attrition bias (favouring acupuncture); three were subject to performance bias (favouring acupuncture) and one to detection bias (favouring acupuncture). Three studies utilised electro-acupuncture (EA) with the remainder using manual acupuncture (MA) without electrical stimulation. All studies used 'formula acupuncture' except for one, which used trigger points.Low quality evidence from one study (13 participants) showed EA improved symptoms with no adverse events at one month following treatment. Mean pain in the non-treatment control group was 70 points on a 100 point scale; EA reduced pain by a mean of 22 points (95% confidence interval (CI) 4 to 41), or 22% absolute improvement. Control group global well-being was 66.5 points on a 100 point scale; EA improved well-being by a mean of 15 points (95% CI 5 to 26 points). Control group stiffness was 4.8 points on a 0 to 10 point; EA reduced stiffness by a mean of 0.9 points (95% CI 0.1 to 2 points; absolute reduction 9%, 95% CI 4% to 16%). Fatigue was 4.5 points (10 point scale) without treatment; EA reduced fatigue by a mean of 1 point (95% CI 0.22 to 2 points), absolute reduction 11% (2% to 20%). There was no difference in sleep quality (MD 0.4 points, 95% CI -1 to 0.21 points, 10 point scale), and physical function was not reported.Moderate quality evidence from six studies (286 participants) indicated that acupuncture (EA or MA) was no better than sham acupuncture, except for less stiffness at one month. Subgroup analysis of two studies (104 participants) indicated benefits of EA. Mean pain was 70 points on 0 to 100 point scale with sham treatment; EA reduced pain by 13% (5% to 22%); (SMD -0.63, 95% CI -1.02 to -0.23). Global well-being was 5.2 points on a 10 point scale with sham treatment; EA improved well-being: SMD 0.65, 95% CI 0.26 to 1.05; absolute improvement 11% (4% to 17%). EA improved sleep, from 3 points on a 0 to 10 point scale in the sham group: SMD 0.40 (95% CI 0.01 to 0.79); absolute improvement 8% (0.2% to 16%). Low-quality evidence from one study suggested that MA group resulted in poorer physical function: mean function in the sham group was 28 points (100 point scale); treatment worsened function by a mean of 6 points (95% CI -10.9 to -0.7). Low-quality evidence from three trials (289 participants) suggested no difference in adverse events between real (9%) and sham acupuncture (35%); RR 0.44 (95% CI 0.12 to 1.63).Moderate quality evidence from one study (58 participants) found that compared with standard therapy alone (antidepressants and exercise), adjunct acupuncture therapy reduced pain at one month after treatment: mean pain was 8 points on a 0 to 10 point scale in the standard therapy group; treatment reduced pain by 3 points (95% CI -3.9 to -2.1), an absolute reduction of 30% (21% to 39%). Two people treated with acupuncture reported adverse events; there were none in the control group (RR 3.57; 95% CI 0.18 to 71.21). Global well-being, sleep, fatigue and stiffness were not reported. Physical function data were not usable.Low quality evidence from one study (38 participants) showed a short-term benefit of acupuncture over antidepressants in pain relief: mean pain was 29 points (0 to 100 point scale) in the antidepressant group; acupuncture reduced pain by 17 points (95% CI -24.1 to -10.5). Other outcomes or adverse events were not reported.Moderate-quality evidence from one study (41 participants) indicated that deep needling with or without deqi did not differ in pain, fatigue, function or adverse events. Other outcomes were not reported.Four studies reported no differences between acupuncture and control or other treatments described at six to seven months follow-up.No serious adverse events were reported, but there were insufficient adverse events to be certain of the risks. AUTHORS' CONCLUSIONS: There is low to moderate-level evidence that compared with no treatment and standard therapy, acupuncture improves pain and stiffness in people with fibromyalgia. There is moderate-level evidence that the effect of acupuncture does not differ from sham acupuncture in reducing pain or fatigue, or improving sleep or global well-being. EA is probably better than MA for pain and stiffness reduction and improvement of global well-being, sleep and fatigue. The effect lasts up to one month, but is not maintained at six months follow-up. MA probably does not improve pain or physical functioning. Acupuncture appears safe. People with fibromyalgia may consider using EA alone or with exercise and medication. The small sample size, scarcity of studies for each comparison, lack of an ideal sham acupuncture weaken the level of evidence and its clinical implications. Larger studies are warranted.

The SMILE study -- safety of methotrexate in combination with leflunomide in rheumatoid arthritis.

OBJECTIVE: To assess the safety of treating patients with rheumatoid arthritis with a combination of methotrexate (MTX) and leflunomide (LEF) in comparison to MTX monotherapy, in clinical practice. METHODS: The Safety of Methotrexate in Combination with Leflunomide in Rheumatoid Arthritis (SMILE) study was a multicenter, observational, cross-sectional, retrospective safety study. The study was conducted by the Optimising Patient Outcomes in Australian Rheumatology-Quality Use of Medicines Initiative (OPAL QUMI). Data were deidentified for patient, clinic, and clinician prior to collection from 13 participating rheumatology practices (25 rheumatologists). Comparative analysis of safety for the different treatments, primarily with regard to neutropenia and liver abnormalities, was performed. RESULTS: In total, 2975 patients were included in the study: 74% female, 26% male, mean age 62 years (SD 13.6). Distribution of therapy: MTX monotherapy 52.2%, LEF monotherapy 7.3%, MTX plus LEF 13.9%, and neither MTX nor LEF 26.6%. Comorbid liver disease was reported in 8.1% of patients. Liver function abnormalities were reported in 12% of the MTX monotherapy group, 16% of the LEF monotherapy group, 19% of the MTX-LEF combination group, and 14% of the group not taking either drug. Neutropenia was reported in 2.3% of the MTX monotherapy group, 5.5% of the LEF monotherapy group, 3.9% of the MTX-LEF combination group, and 4.2% of the group not taking either drug. CONCLUSION: The combination of MTX and LEF was well tolerated, with adverse events comparable to those of monotherapy and the other nonbiologic disease-modifying antirheumatic drug treatment group.

Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate.

OBJECTIVE: To determine cancer risk in a cohort of 459 rheumatoid arthritis (RA) patients treated with methotrexate in community practice. METHODS: All RA patients who started methotrexate prior to June 1986 and were attending 1 of 6 rheumatologists were studied. Demographic data were matched to the State Cancer Registry to identify all malignancies (except nonmelanoma skin cancer) for 1983-1998, and to the National Death Index to identify all deaths to the end of 1999. Followup started on the date when methotrexate was started and ended either on the last confirmed date on which the patient was seen by the rheumatologist or at death. Standardized incidence ratios (SIRs) were calculated using state population cancer rates stratified by sex, age (in 5-year groups), and calendar year. RESULTS: There were 4,145 person-years of followup (average 9.3 years). Eighty-seven malignancies were identified (14 before, 64 during, and 9 after the followup period). There was an estimated 50% excess risk of malignancy among methotrexate-exposed RA patients relative to the general population (SIR 1.5, 95% confidence interval [95% CI] 1.2-1.9), with a 3-fold increase in melanoma (SIR 3.0, 95% CI 1.2-6.2), a 5-fold increase in non-Hodgkin's lymphoma (SIR 5.1, 95% CI 2.2-10.0), and an almost 3-fold increase in lung cancer (SIR 2.9, 95% CI 1.6-4.8). CONCLUSION: Compared with the general population, methotrexate-treated RA patients have an increased incidence of melanoma, non-Hodgkin's lymphoma, and lung cancer. There may be a role for regular skin cancer screening for all RA patients, particularly those receiving immunosuppressive therapy.