Ricardo Blanco

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors. METHODS: In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis. RESULTS: At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib. CONCLUSIONS: In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).

Abstract Objective. To assess the possible differences between children (⩽ 20 years) and adults (&gt; 20 years) with Henoch‐Schönlein purpura (HSP). Methods. A retrospective study of an unselected population of patients with HSP who presented to our teaching hospital between 1975 and 1994. Patients were classified as having HSP according to the criteria proposed by Michel et al. Results. Following the above‐mentioned criteria, 162 white patients (113 male and 49 female) were classified as having HSP; 46 of the patients were adults (mean ± SD age 53.2 ± 16.9 years) and 116 were children (6.9 ± 3.1 years). We were unable to identify any precipitating event in 72% of the adults and 66% of the children. The frequency of previous drug treatment, primarily antibiotics or analgesics, was similar in both groups, whereas previous upper respiratory tract infection was more frequent among the children ( P &lt; 0.02). At symptom onset, cutaneous lesions were the main clinical manifestation in both groups. However, adults had a lower frequency of abdominal pain ( P &lt; 0.008) and fever ( P &lt; 0.01), and a higher frequency of joint symptoms ( P &lt; 0.001). During the clinical course, adults had more frequent ( P &lt; 0.001) and severe renal involvement. An increased erythrocyte sedimentation rate was also more frequent in the adults ( P &lt; 0.001). Adults required more aggressive therapy, consisting of steroids ( P &lt; 0.002) and/or cytotoxic agents ( P &lt; 0.001). The outcome was relatively good in both age groups, with complete recovery in 107 children (93.9%) and in 33 adults (89.2%) after a mean ± SD followup of 19.4 ± 27.7 (median 12) and 21.8 ± 33.5 (median 15) months, respectively. Conclusion. In adulthood, HSP, as defined by the criteria proposed by Michel et al, represents a more severe clinical syndrome, with a higher frequency of renal involvement. However, the final outcome of HSP is equally good in patients of both age groups.

OBJECTIVE: To assess the efficacy and safety of tocilizumab plus methotrexate (MTX) versus MTX alone in preventing structural joint damage and improving physical function and disease activity in patients with moderate-to-severe rheumatoid arthritis and inadequate responses to MTX. METHODS: A total of 1,196 patients were enrolled in a 2-year, randomized, double-blind, placebo-controlled trial. Patients received tocilizumab (8 mg/kg or 4 mg/kg) or placebo every 4 weeks plus MTX. Rescue treatment was available from week 16. Results from year 1 are presented. RESULTS: Mean change in the total Genant-modified Sharp score was 0.29 and 0.34 with tocilizumab 8 mg/kg plus MTX and 4 mg/kg plus MTX, respectively, versus 1.13 with placebo plus MTX (P < 0.0001 for both comparisons). Analysis of variance of the area under the curve for change from baseline in the disability index of the Health Assessment Questionnaire showed greater decreases with tocilizumab 8 mg/kg and 4 mg/kg (-144.1 and -128.4 units, respectively) than with placebo (-58.1 units; P < 0.0001 for both comparisons). Proportions of patients with American College of Rheumatology 20%, 50%, and 70% improvement and with Disease Activity Score in 28 joints remission were higher in those receiving 8 mg/kg tocilizumab than in those receiving placebo (P < 0.0001 for all comparisons). The safety profile of tocilizumab was consistent with the profiles in previous studies. Infections were the most common adverse and serious adverse events. CONCLUSION: The findings of this study show that tocilizumab plus MTX results in greater inhibition of joint damage and improvement in physical function than does MTX alone. Tocilizumab has a well-characterized safety profile.

OBJECTIVE: To assess the features and therapeutic response of visual manifestations and cerebrovascular accidents (CVA) in giant cell (temporal) arteritis (GCA) and to identify the predictors for permanent visual loss (VL) and CVA in GCA. METHODS: Two hundred thirty-nine patients with biopsy-proven GCA were included in a retrospective multicenter study. Data on demographic, clinical, and laboratory features were collected. The predictors were identified by a forward stepwise nonconditional logistic regression analysis. RESULTS: Visual involvement was observed in 69 patients, and 34 had permanent VL. The diagnostic delay since the onset of visual symptoms was longer in the 11 patients with bilateral VL. The interval to involvement of the second eye was 5 days. The predictors of permanent VL were transient VL, jaw claudication, normal levels of liver enzymes, and absence of constitutional syndrome. Partial improvement of visual acuity was observed in 8 patients. After adjustment for the treatment regimen (intravenous pulse methylprednisolone versus oral prednisone), early treatment (within the first day of VL) was the only predictor of improvement. CVA, observed in 8 patients, involved the vertebral-basilar territory in 4. CVA was more frequent in patients with visual symptoms, appearing shortly after VL (median 7 days) and despite appropriate therapy. Predictors of CVA were permanent VL and jaw claudication. CONCLUSION: In GCA, the risk of permanent VL is increased in patients with transient VL and/or jaw claudication, and decreased in those with elevated liver enzyme levels and/or constitutional syndrome. Partial therapeutic success is more probable if treatment is started within the first day of VL. CVA is more likely in patients with permanent VL and/or jaw claudication, often developing despite appropriate corticosteroid therapy.