Effects of Intravenous Golimumab on Health-Related Quality of Life in Patients with Ankylosing Spondylitis: 28-Week Results of the GO-ALIVE Trial.

OBJECTIVE: Evaluate the effect of intravenous golimumab on health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS) through week 28 of the phase III, multicenter, randomized, double-blind, placebo-controlled GO-ALIVE study. METHODS: Adult patients (n = 208) were randomized to IV golimumab 2 mg/kg (n = 105) at weeks 0, 4, and 12 and every 8 weeks or placebo (n = 103) at weeks 0, 4, and 12, with crossover to golimumab 2mg/kg at weeks 16, 20, and every 8 weeks. General HRQoL was evaluated using the Short Form Health Survey (SF-36) Physical Component Summary/Mental Component Summary (PCS/MCS), and the EQ VAS, and AS disease-specific HRQoL was assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) instrument. RESULTS: Mean improvements from baseline in SF-36 PCS were greater in the golimumab group versus the placebo group at weeks 8 and 16 (6.8 vs 2.1 and 8.5 vs 2.9, respectively; P < .001); similar results were observed for SF-36 MCS (5.6 vs 1.7 and 6.5 vs 0.8, respectively; P < .001). Mean improvement in each of 8 subscale scores of the SF-36 were also greater for golimumab-treated patients versus placebo at weeks 8 and 16. Mean improvements in EQ VAS and ASQoL were greater in the golimumab group versus placebo at week 8 and week 16. Greater proportions of golimumab-treated patients had clinically meaningful improvement in SF-36 PCS, SF-36 MCS, EQ VAS, and ASQoL at weeks 8 and 16; improvements in SF-36 PCS/MCS, EQ VAS, and ASQoL were maintained through week 28. CONCLUSIONS: Golimumab-treated patients had greater mean improvements in HRQoL measures compared with placebo through week 16. Clinically meaningful improvements were observed as early as week 8 and continued through week 28.

Early effects of tocilizumab in the treatment of moderate to severe active rheumatoid arthritis: a one-week sub-study of a randomised controlled trial (Rapid Onset and Systemic Efficacy [ROSE] Study).

OBJECTIVES: Tocilizumab has demonstrated efficacy in managing rheumatoid arthritis (RA) from week 2 onward. This sub-study assessed effects of tocilizumab plus disease-modifying anti-rheumatic drugs (DMARDs) during the first week of therapy. METHODS: Rapid Onset and Systemic Efficacy was a 24-week, randomised, double-blind, placebo-controlled, parallel-group trial. Adults with moderate to severe active RA taking DMARDs received tocilizumab 8 mg/kg (or placebo) plus DMARDs every 4 weeks. Data were analysed from the first 62 patients at designated study sites who agreed to clinical evaluation and blood sampling at days 3 and 7 and had C-reactive protein levels ≥1 mg/dl. Outcomes included American College of Rheumatology core data set measures, disease activity score using 28 joints (DAS28) and routine assessment of patient index data 3 (RAPID3) scores. RESULTS: Baseline evaluations were similar between groups (tocilizumab, n=40; placebo, n=22). Patient global assessments of disease activity and pain improved significantly in favour of tocilizumab (mean change from baseline to day 7: -16.2 [tocilizumab], 0.8 [placebo] [p=0.005] and -12.2 [tocilizumab], 1.4 [placebo] [p=0.01], respectively). Physician global assessment of disease activity also improved more with tocilizumab (-15.4 [tocilizumab], -5.6 [placebo] [p=0.05]). Changes from baseline in tender/swollen joint counts, physical function and RAPID3 scores were not significantly different between groups. DAS28 significantly improved with tocilizumab versus placebo at day 7 (-1.16 [tocilizumab], -0.27 [placebo] [p=0.007]). CONCLUSIONS: Tocilizumab showed significant improvement in patient-reported disease activity, pain and DAS28 score as early as day 7 after first infusion, earlier than physician-reported measures, which may take longer to manifest.

Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study.

OBJECTIVE: To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed. METHODS: The rapid onset and systemic efficacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups. RESULTS: The primary efficacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were significantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Significant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were consistent with the known tocilizumab safety profile; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively. CONCLUSIONS: This study demonstrated the efficacy of tocilizumab in improving measures of disease activity in patients with RA who failed to respond adequately to DMARD therapy. Rapid improvement in clinical outcomes was demonstrated in a substudy as early as week 1 as shown by DAS28 scores, patient measures and C-reactive protein. TRIAL REGISTRY NO: NCT00531817.

Effectiveness and safety of etanercept in subjects with RA who have failed infliximab therapy: 16-week, open-label, observational study.

BACKGROUND AND OBJECTIVE: Tumor necrosis factor (TNF) antagonists, including etanercept (a soluble TNF receptor) and infliximab (an anti-TNF monoclonal antibody) are used in the treatment of patients with rheumatoid arthritis (RA). The purpose of this study was to evaluate the effectiveness and safety of 50 mg etanercept weekly in subjects with RA who have failed infliximab therapy. METHODS: This phase 4, multicenter, open-label, single-arm, 16-week observational study enrolled subjects who had experienced primary (failure to achieve an initial response) or secondary (failure to maintain an initial response) infliximab failures. Effectiveness was measured using European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) response criteria and laboratory assessments were used to evaluate levels of inflammation, lymphotoxin alpha, drug concentrations, and antibodies to infliximab. Safety endpoints included incidence of serious adverse events. CLINICAL TRIAL REGISTRATION: This trial was registered under U.S. National Institutes of Health ClinicalTrials.gov identifier NCT00099554. RESULTS: At week 16, over half (62%; 95% CI = 55, 69) of all subjects in the trial achieved a good or moderate EULAR response (DAS28) with etanercept. Using ACR criteria, after 16 weeks of etanercept therapy, 45% (95% CI = 38, 52) of all subjects had achieved an ACR20 response. Benefits were noted in tender and swollen joint counts, subject and physician global assessments, joint pain, and the Health Assessment Questionnaire. Outcomes were similar between subjects with primary and secondary infliximab failures. Levels of lymphotoxin alpha did not appear to affect response to etanercept. Potential limitations included the lack of a washout period, short duration of the trial, and the number of subjects who did not receive all doses of etanercept. CONCLUSION: In this open-label, uncontrolled study, subjects with moderate to severe RA who failed to respond or who lost their initial response to infliximab safely benefited from receiving etanercept.

Scleredema adultorum of Buschke: a case report and review of the literature.

OBJECTIVES: To present a case of scleredema adultorum of Buschke associated with hypergammaglobulinemia and review the literature pertaining to this disease. METHODS: Search of MEDLINE (PubMed) was performed using the words "Scleredema Adultorum." Only cases in the English language, with pertinent clinical information for analysis, were included. RESULTS: We present a case of scleredema associated with hypergammaglobulinemia. The skin findings had been progressive for 2 years before he was diagnosed with scleredema. Our patient was found to have a B-cell lymphoma before being diagnosed with scleredema. The progression of skin thickening halted with no apparent correlation to immunosuppressive therapies or chemotherapeutic agents. A total of 165 cases of scleredema adultorum are described in the literature. There are 3 types of scleredema adultorum. Type 1 is usually preceded by a febrile episode and resolves spontaneously. Type 2 is associated with developing paraproteinemias including multiple myeloma. Type 3 is associated with diabetes mellitus. CONCLUSIONS: Scleredema adultorum of Buschke is a rare disorder which is sometimes associated with hypergammaglobulinemia; our patient had a B-cell lymphoma. Physicians should suspect scleredema in any patient with diffuse skin thickening where the hands and feet are spared, particularly if diabetes or a preceding febrile episode were present. Once the diagnosis of scleredema is made, evidence for the presence of hypergammaglobulinemia should be sought.

Cardiopulmonary exercise testing with pulmonary artery catheterization detects early pulmonary vasculature changes in patients with connective tissue diseases.

Pulmonary hypertension is a well-recognized complication of connective tissue diseases (CTD), with clinical symptoms typically limited to those with relatively advanced disease. The objective of this study was to identify patients with early pulmonary vasculature changes using cardiopulmonary exercise testing with pulmonary artery catheterization. Four patients with CTD and normal Doppler echocardiogram results identified as high risk for pulmonary hypertension on the basis of disease process underwent cardiopulmonary exercise testing with pulmonary artery catheterization. All patients had normal mean pulmonary artery pressures at rest (<25 mmHg), but exhibited an abnormal rise in mean pulmonary artery pressure with exercise. Cardiopulmonary exercise testing should be considered in patients at high risk for pulmonary hypertension to identify those individuals who may benefit from early therapeutic intervention.