Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

OBJECTIVE: To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN). METHODS: A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26. RESULTS: A dose-response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7-95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9-75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5-10%) and severe infections (10% vs. 4.8-5.0%) were reported with 240 mg BI 655064. CONCLUSION: The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.

Kikuchi Fujimoto disease: A series of three cases

INTRODUCTION: Kikuchi-Fujimoto disease (KFD) is a  rare self-limited disorder manifested by painful cervical lymphadenopathies commonly associated with fever and night sweats.This is a series of three female patients presenting with fever and lymphadenopathies diagnosed with KFD.CASE: The first case is a 34-year-old female admitted due to fever of 10 days associated with lymphadenopathies and joint pains.Excision biopsy done showed necrotizing histiocytic lymphadenitis consistent with KFD.Other laboratories showed hypocomplementemia, positive ANA and anti-dsDNA.Patient was discharged improved with low dose oral corticosteroid and hydroxychloroquine.The second case is a 53-year-old female with fever,lymphadenopathies,polyarthritis and morning stiffness.Biopsy of the cervical lymph node was done showing KFD and lupus serologies (ANA 1:640 speckled, anti-dsDNA and anti-Smith) revealed positive results as well.Patient was then diagnosed with SLE and was started on low dose oral corticosteroid and hydroxychloroquine which resulted to resolution of fever and gradual resolution of lymph nodes on out-patient follow up.The last case is a 45-year-old female admitted due to persistent fever, painful lymphadenopathies and headache. Serological work-up including autoantibody tests for SLE were all unremarkable but showed associated iron deficiency anemia. Biopsy of the cervical lymph node showed Kikuchi's disease. Patient was discharged with oral methylprednisolone.CONCLUSION: The rarity of KFD makes defining an autoimmune etiology a challenge to clinicians.Careful disease course follow up is then recommended for patients who initially lack parameters for SLE diagnosis.

Rituximab for refractory anemia and thrombocytopenia in a patient with systemic lupus erythematosus

INTRODUCTION: Hematologic manifestations of Systemic Lupus Erythematosus (SLE) such as hemolytic anemia, leucopenia and thrombocytopenia are among the common causes of morbidity and hospitalization among patients. This is a case report of a patient presenting with refractory cytopenias.CASE: The  patient  is  a  42-year-old  female,  diagnosed with  SLE,  having  met  the  Systemic  Lupus  Erythematosus  International  Collaboration  Clinics  Criteria  for  diagnosis Persistent  serositis  (pleural  effusion  and  ascites) and worsening of anemia prompted treatment with oral corticosteroid (prednisone 1.0 mg per kg per day) which showed improvement of shortness of breath and  pleural effusion. Cytopenias persisted despite increasing IV pulse steroid to 6.0  mkd  prednisone then further to 13 mkd prednisone.Rituximab given as 1.0 g infusion once every two weeks for two doses which resulted to improvement of anemia, thrombocytopenia and serositis.  CONCLUSION: Hematologic manifestations may present as life threatening complications of lupus.Most cases are responsive  to  corticosteroid  therapy,however,in a few refractory cases,less used conventional treatment such as rituximab,may provide significant response.