1,721,024 research outputs found
Trial of Anifrolumab in Active Systemic Lupus Erythematosus.
No full textBACKGROUND:
Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point.
METHODS:
We randomly assigned patients in a 1:1 ratio to receive intravenous anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate.
RESULTS:
A total of 362 patients received the randomized intervention: 180 received anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P = 0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received anifrolumab. There was one death from pneumonia in the anifrolumab group.
CONCLUSIONS:
Monthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with anifrolumab than with placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT02446899.).status: Publishe
Assessment of Disease Activity in Large-vessel Vasculitis: Results of an International Delphi Exercise
No full textOBJECTIVE:
To arrive at consensus for candidate outcomes for disease activity assessment in large-vessel vasculitis (LVV) in clinical trials.
METHODS:
A Delphi survey including 99 items was circulated among international experts for 3 rounds.
RESULTS:
Fifty-seven items were accepted for both giant cell arteritis and Takayasu arteritis. Sixty-seven percent of experts voted to have a common approach for both diseases with additional disease-specific items such as weight loss, scalp tenderness/necrosis, morning stiffness, dizziness, visual symptoms, and imaging.
CONCLUSION:
This study highlights similarities and differences in experts' perspectives for assessing clinical activity in LVV and may guide a consensus-driven core set of validated outcomes.sponsorship: NIAMS NIH HHS|U01 AR051874, NIAMS NIH HHS|U54 AR057319, NCRR NIH HHS|U54 RR019497status: Publishe
Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts
No full textOBJECTIVE:IgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought to identify key IgG4-RD phenotypes. METHODS:We used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis. RESULTS:In the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1-3 (316, 178 and 445 mg/dL, respectively, p<0.001). CONCLUSION:We identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment
Biologicals bij systeemvasculitis
No full textThe use of biologicals in vasculitis
Tumor necrosis factor antagonists have proven
to be unsuccessful in giant cell arteritis and
ANCA-associated small vessel vasculitis, but
may have some indications in Behçetâs disease.
Rituximab, a monoclonal antibody
directed against CD20-positive lymphocytes,
is the treatment of choice in ANCA-associated
vasculitis, both in remission-induction and in
maintenance treatment. Tocilizumab, an interleukin-
6 antagonist, is a welcome new treatment
for patients with giant cell arteritis, who
have serious side effects on steroids or who
are frequently relapsing under a monotherapy
with steroids.status: Publishe
Fluorodeoxyglucose Positron Emission Tomography for Giant Cell Arteritis
No full textstatus: Publishe
Use of FDG-PET scan for the assessment of large vessel vasculitis
No full textTemporal artery biopsy will only detect (part of) the cranial forms of giant cell arteritis. For the large vessel variant of this type of vasculitis, FDG-PET is the technique of choice. Since treatment of large vessel vasculitis implies long-term treatment with steroids, it is important to have a firm diagnosis. I suggest performing a FDG-PET scan in every patient in whom large vessel vasculitis is suspected and in whom the temporal artery biopsy is negative. In the follow-up of giant cell arteritis patients, we can rely on clinical symptoms and inflammatory parameters to monitor disease activity and to adapt our treatment and do not need to repeat FDG-PET scan. In Takayasu arteritis, follow-up FDG-PET scans are probably necessary to assess ongoing inflammation, but prospective studies are lacking.status: Publishe
Long-term methylphenidate intake in chronic fatigue syndrome
No full textObjective: Concentration disturbances are frequent in chronic fatigue syndrome (CFS). In a placebo-controlled double-blind crossover study, methylphenidate over 4 weeks was superior to placebo in the relief of fatigue and concentration disturbance. This observational study describes the effect of long-term methylphenidate intake on fatigue, concentration, and daily life activities, as reported by the patients themselves.
Methods: A questionnaire was sent to all CFS patients who were prescribed methylphenidate at the general internal medicine department of a university hospital between August 2004 and February 2007, for possible improvement of concentration difficulties and fatigue.
Results: Out of 194 consecutive patients, 149 (76.8%) sent the questionnaire back. At the time of the questionnaire, 65.3% had stopped the intake of methylphenidate, 34.7% still took it daily or occasionally. Among the patients who continued methylphenidate, 48% reported an at least 50% improvement of fatigue, and 62% reported an at least 50% improvement of concentration difficulties. This continued intake of methylphenidate resulted in more working hours in these patients. Side effects (agitation, palpitations, and dry mouth) were reported significantly more in patients who had stopped methylphenidate than in those who still took it.
Conclusion: The long-term intake of methylphenidate by CFS patients with concentration difficulties has a positive effect in about one out of three patients.sponsorship: nonestatus: Publishe
Een 68-jarige man met vermagering, botletsels, vermoeidheid en inflammatoir bloedbeeld
No full textstatus: Publishe
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