Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study.

OBJECTIVES: To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. METHODS: SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)-erythrocyte sedimentation rate (ESR) over 6 months. RESULTS: 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3-ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3-ESR at 6 months was significantly greater in rituximab than TNFi patients: -1.5 (0.2) vs -1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (-1.7 vs -1.3; p=0.017) but not intolerance (-0.7 vs -0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3-ESR with rituximab than with TNFi (-1.6 (0.3) vs -1.2 (0.3); p=0.011), particularly those switching because of inefficacy (-1.9 (0.3) vs -1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. CONCLUSIONS: These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy.

Adjunctive anakinra in patients with active rheumatoid arthritis despite methotrexate, or leflunomide, or cyclosporin-A monotherapy: a 48-week, comparative, prospective study.

OBJECTIVE: To assess the efficacy and safety of anakinra (ANK) as an add-on therapy in RA patients with inadequate response to monotherapy with non-biological DMARDs. METHODS: A 48-week comparative, prospective study of patients with active RA [mean 28-joint disease activity score (DAS28): 6.81], despite MTX (n = 48), or LEF (n = 42), or CSA (n = 38) treatment, in whom ANK (100 mg/daily SC) was given with corticosteroid cream topical application. RESULTS: At 24 and 48 weeks the patient percentages meeting the ACR20 response criteria were 57 and 73%, respectively, 33 and 41% met ACR50, while 15 and 23% met ACR70. Significant improvements in number of swollen and tender joints, HAQ, pain, global disease assessment, CRP and haemoglobin from baseline to 24 and 48 weeks were evident. DAS28 decreased at 24 weeks (- 1.68; 95% CI - 1.46, - 1.90; P < 0.0001), as well as at study end (- 2.24; 95% CI - 2.01, - 2.47; P < 0.0001). Subgroup analysis revealed a significantly weaker response in terms of pain and DAS28 in patients treated with concomitant CSA. The most common ANK-related adverse event was injection-site reaction (29%), being less frequent in male patients, as well as in patients treated with CSA. There were 17 withdrawals, 6 of them due to inefficacy. No opportunistic infections or new safety signals were observed. CONCLUSION: Considering the limitations of an open-label study, addition of ANK appears to be an effective and well-tolerated treatment option for many RA patients with inadequate responses to non-biologic DMARDs in clinical practice.

Prevalence and management of rheumatoid arthritis in the general population of Greece--the ESORDIG study.

OBJECTIVE: To assess the prevalence and management of rheumatoid arthritis (RA) in the general adult population of Greece. METHODS: This cross-sectional study was conducted on the total adult population (> or =19 yrs old) of seven communities (8,547 subjects), and on 2,100 out of 5,686 randomly selected subjects in two additional communities. The study, based on a standardized questionnaire and clinical evaluation and laboratory investigation when necessary, was carried out by rheumatologists who visited the target population at their homes. Diagnosis of RA was based on the American College of Rheumatology (ACR) 1987 criteria. RESULTS: A total of 8,740 subjects participated (response rate 82.1%). RA was diagnosed in 59 individuals. The prevalence of RA was 0.68% (95% CI 0.51-0.85); it was significantly higher in females than males (P< 0.0005), and increased significantly with age up to and including the 50-59-yr-old group (P< 0.002), and then decreased slightly. On their first medical visit, 19% (95% CI 9.7-30.9) of the RA patients had consulted a rheumatologist, while during the first year after disease onset, 61% (95% CI 48.6-73.4) had done so. Early consultation with a rheumatologist and disease-modifying anti-rheumatic drug (DMARD) combination therapy were negatively associated with ACR functional classes II-IV [adjusted odds ratios 0.18 (95% CI 0.04-0.85) and 0.17 (95% CI 0.04-0.72), respectively]. CONCLUSIONS: The prevalence of RA in the general adult population of Greece is similar to that in many other European countries; early consultation with a rheumatologist and DMARD combination therapy are associated with a better RA outcome.

Seronegative spondyloarthropathies in Greece: a population-based study of prevalence, clinical pattern, and management. The ESORDIG study.

The objective of this study was to determine the prevalence, clinical pattern, and management of seronegative spondyloarthropathies (SpA) in the general adult population of Greece. This population-based study was conducted on a target adult (> or =19-year-old) population of 14,233 subjects by rheumatologists who visited households in nine dispersed areas. An interview (standardized questionnaire) was conducted, clinical evaluation and laboratory investigation were done, and established diagnostic classification criteria were used. The age-adjusted and sex-adjusted prevalence (prevalence(asa)) of SpA was 0.49% [95% confidence interval (CI): 0.38-0.60], with a male to female ratio of 5.5:1; the prevalence increased with age until the 59- to 68-year-old age group and declined thereafter. The prevalence(asa) of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) was 0.24% (95% CI: 0.16-0.32) and 0.17% (95% CI: 0.10-0.24), respectively. The mean age (years) at onset was younger in AS (25.83 +/- 6.5) than in PsA (45.24 +/- 12.94) (p < 0.01). Familial clustering was noticed in 5.3% of AS probands. Sacroiliitis was observed in 39.8% and asymmetrical oligoarthritis in 40.6% of PsA patients. Fifty-nine percent of SpA patients had previously visited rheumatologists (91.3% diagnosed correctly vs 11.6% of those who visited other specialists, p < 0.0005); 56.5% of the former had taken disease-modifying antirheumatic drugs compared to none of the latter. The SpA in Greeks are as common as in other European Caucasians, with a high male preponderance. The PsA onset occurs at an older age than AS and frequently presents with a spondylitic pattern. The correct diagnosis was arrived at and appropriate treatment was given when patients consulted rheumatologists.

The burden of the rheumatic diseases in the general adult population of Greece: the ESORDIG study.

OBJECTIVE: To estimate the burden of rheumatic diseases in terms of disability and health-care utilization in the Greek general adult population. METHODS: The study was conducted on the total adult population of seven communities (8547 subjects), as well as on 2100 out of 5686 randomly selected subjects in an additional two communities. Rheumatologists visited the participants at their homes to assess the prevalence of six morbidity indicators concerning disability and health-care utilization associated with rheumatic diseases or other major disease groups. RESULTS: The participation rate in the study was 82.1%. The prevalence of chronic health problems, long-term disability, short-term disability, physician office visits and prescription or non-prescription drug use due to rheumatic diseases in the total target adult population was 14.3, 4.3, 2.9, 2.8, 7.2 and 2.0%, respectively. Compared with all other major disease groups, rheumatic diseases were the most common cause of chronic health problems (38.7%), long-term disability (47.2%), short-term disability (26.2%) and physician office visits (20.5%), while they ranked second for the use of prescription (24.0%) or non-prescription drugs (17.7%). Rheumatic diseases were the main cause of morbidity in five out of six indicators in subjects aged < or =65 yr. Logistic regression analysis revealed an association of female gender, age > or =45 yr and obesity with almost all morbidity indicators related to rheumatic diseases. CONCLUSION: These findings suggest that rheumatic diseases constitute a major public health problem and should be considered in planning undergraduate and postgraduate medical education, research and health-care services.

Intestinal pseudo-obstruction and ureterohydronephrosis as the presenting manifestations of relapse in a lupus patient.

Intestinal pseudo-obstruction (IPO) is a rare complication of systemic lupus erythematosus (SLE). We present a 32-year old female with SLE for seven years. She was admitted with profound fatigue, frequent vomiting, colicky abdominal pain, diarrhoea and intermittent dysuria for the past 12 months. Imaging studies revealed dilated small and large bowel loops with thickened intestinal wall and multiple fluid levels. Urinary tract involvement was also demonstrated. The patient responded well to immunosuppressive treatment. IPO in the context of SLE has been described only in anecdotal case reports. Half of the cases developed this complication during the course of lupus as in the present case. Concomitant ureterohydronephrosis was present in approximately two-thirds of the cases. Early recognition of the syndrome is necessary for the institution of the appropriate medical treatment and prevention of inappropriate surgical intervention.

Systemic lupus erythematosus and myelofibrosis.

The coexistence of systemic lupus erythematosus and myelofibrosis is a rare occurrence. A review of the literature available to us revealed only five other patients with this combination. We have recently encountered a patient in whom these two diseases existed concomitantly, and in this report we shall describe the clinical course of our patient and discuss it in comparison with the patients described previously.

Comparison of two dosage schedules of gold salts in the treatment of rheumatoid arthritis. Relationship of serum gold levels to therapeutic response.

Two doses of gold sodium thiomalate were compared for their effect on rheumatoid arthritis. Thirty-seven patients with active disease for longer than 6 months were treated with 25 mg of gold sodium thiomalate for an average of 29.6 weeks, then at biweekly or monthly intervals to complete 2 years of treatment. Thirty-eight patients were given more than twice as much gold salt at the same intervals on a flexible dose schedule that produced serum gold levels which averaged 332 microgram/dl during the weekly injection phase. No differences were observed in the therapeutic responses of the two groups. Therefore the minimal dose of gold sodium thiomalate required to induce a response in rheumatoid arthritis is 25 mg or less per week. Serum gold levels in the steady state varied between 95 and 386 microgram/dl and were not related to response. Serum half-life for gold was calculated for patients who had an excellent response and for those who were treatment failures. The rate at which gold disappeared from serum was not related to therapeutic responses.

Cell-mediated immunity in rheumatoid arthritis.

Cell-mediated immunity in rheumatoid arthritis (RA) was assessed by skin testing with six antigens in 107 patients, 94 of whom were age, sex, and race-matched with healthy individuals or patients with diseases unrelated to immunological abnormalities. 20% of RA patients were anergic. Impaired cell-mediated immunity in the RA patients was manifested by a decrease in the magnitude of skin reactivity as well as a decrease in the incidence of positive reactions to multiple antigens. Depression in cell-mediated immunity was related to age but not to sex, duration of disease, or disease activity. A slight correlation was found between absolute peripheral lymphocyte counts and the number of positive skin tests, and was confirmed by finding an association between lymphocyte counts and the size of skin reactions. A correlation was also found between lymphocyte counts and disease activity. Four explanations of the observed depression in cell-mediated immunity in RA were considered: (1) a preoccupation of the immune mechanism of the host with cell-mediated immunity reactions related to the pathogenesis of the disease; (2) a depression of cell-mediated immune reactivity by a virus infection; (3) depression of cell-mediated immunity by therapy; and (4) immune complex suppression of cell-mediated immunity. No effect of gold therapy was found. The near universal use of salicylates or other anti-inflammatory drugs did not permit investigation of the effect of these drugs on cell-mediated immunity.

Transverse myelopathy in systemic lupus erythematosus. Report of three cases and review of the literature.

Three cases of transverse myelopathy associated with systemic lupus erythematosus were reported, and 23 similar cases previously reported were reviewed. A diagnosis of systemic lupus erythematosus was made in only 60% before the onset of transverse myelopathy. The time of onset of myelopathy was randomly distributed during the disease. The most common presenting neurologic symptom was numbness, or weakness of the legs, or both. A unique association between the acute stage of transverse myelopathy and marked reduction of cerebrospinal fluid glucose concentration was observed. Thirteen patients died, 9 had permanent neurologic deficits, and only 4 recovered nearly normal function. Eight patients had ischemic necrosis of the spinal cord at postmortem examination, and vascular lesions were found in the spinal cord of 3 additional patients. The value of steroid treatment was uncertain. Patients who were started on steroid therapy within 24 hours of the onset of myelopathy may have benefited.