Aarat M. Patel

Interleukin-6 inhibition for treatment of rheumatoid arthritis: A review of tocilizumab therapy

The dawn of the biologic era has been an exciting period for clinical research and patient care in rheumatoid arthritis (RA). Targeted biologic therapies have changed the outcome of this disease and made remission a realistic outcome for many patients. Tocilizumab (TCZ, Actemra®), is a humanized monoclonal antibody against the interleukin 6 receptor and has been approved in many countries for the treatment of moderate to severe RA. There have been a number of important clinical trials demonstrating the efficacy of TCZ in active rheumatoid arthritis. This review summarizes the data on efficacy, patient-reported outcomes, adverse events, and safety from some of these trials. Current trends in clinical practice will be discussed. It is difficult to place TCZ and many new medications in the algorithm of treatment at present. However, the next few years will hopefully reveal their role as we better define abnormal immune processes in individuals with RA.

Certolizumab pegol: a new biologic targeting rheumatoid arthritis.

The past decade has been an exciting period for clinical research and patient care in rheumatoid arthritis. This is mostly due to targeted biologic agents that have changed the outcome of this disease. Certolizumab pegol (Cimzia®, UCB Inc., GA, USA), which targets TNF-α with a different mechanism of action than widely used biologics, was initially investigated for Crohn’s disease but has now been shown to be effective for rheumatoid arthritis. There have been three significant clinical trials demonstrating the efficacy of certolizumab pegol in active rheumatoid arthritis; two with combination methotrexate and one with monotherapy. This article will summarize the data from those trials and compare some of the characteristics of certolizumab pegol to conventional disease-modifying antirheumatic drugs and other biologic agents. Treatment recommendations are beyond the scope of this review; however, with many options available, there will be annotations on current trends in the care of this chronic disease.

Improvement in medication education in a pediatric subspecialty practice

BackgroundThe purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA).MethodsThis study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired t-test (critical P value < 0.05) was performed on individuals who answered both questionnaires.ResultsThere were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (P < 0.0001). Individuals scored the lowest (49%) on the question that addressed MTXs impact on pregnancy and fertility.ConclusionsMTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a familys understanding of their childs medications.

Index of SuspicionCase 1: Decreased Arm Movement in a 5-Week-Old InfantCase 2: Periorbital Edema, Generalized Rash, and Violaceous Discoloration of Eyelids in a 5-Year-Old GirlCase 3: Gradual Abdominal Distension in an 18-Month-Old Boy

The reader is encouraged to write possible diagnoses for each case before turning to the discussion. We invite readers to contribute case presentations and discussions. Please inquire first by contacting Dr Deepak Kamat at DKamat@med.wayne.edu. A 5-week-old, healthy, full-term, female infant, delivered via uncomplicated cesarean section, presents to the emergency department with a gradual decrease of right arm movement during the last 5 days. Although initially calm and comfortable, she now keeps her arm at her side and cries when the parents try to move her arm over her head. She has no history of fever, trauma, swelling, rash, or recent upper respiratory tract illness. The mother’s prenatal laboratory study results, including screening for human immunodeficiency virus, syphilis, hepatitis B, and group B streptococci (at 36 weeks), are negative. Physical examination reveals a well-appearing infant with normal vital signs, who keeps her right arm in a neutral position at her side. There is no swelling or erythema. She cries with palpation of the lateral aspect of her right upper arm and with flexion and abduction of the shoulder. Results of her laboratory studies include the following: white blood cell (WBC) count, 13,800/μL (13.8 × 109/L) with 63% neutrophils, 27% lymphocytes, and 10% monocytes; hemoglobin, 10.2 g/dL (102 g/L); platelet count, 548 × 103/μL(548 × 109/L); erythrocyte sedimentation rate (ESR), 93 mm/h; and C-reactive protein (CRP), 6.4 mg/dL (64 mg/L). Shoulder radiography reveals a lytic lesion of the proximal right humerus (Fig 1). An additional imaging study and surgical procedure establish the diagnosis. Figure 1. Shoulder radiograph showing a lytic lesion of the proximal humerus. A previously healthy 5-year-old girl presents with severe fatigue, dysphagia, and swelling of the face and neck. Two weeks earlier she developed symptoms of upper respiratory tract infection, halitosis, and fever. …

Canakinumab for the treatment of adult and pediatric cryopyrin‐associated periodic syndromes (CAPS)

The cryopyrin‐associated periodic syndromes (CAPS) comprise three rare autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle–Wells syndrome, and neonatal‐onset multisystem inflammatory disorder. A mutation in the NLRP3 (CIAS1) gene, encoding cryopyrin, leads to inflammation and results in fever, chills, urticarial rash, arthralgias, conjunctivitis, and other difficult‐to‐control systemic features. Major advances in understanding interleukin‐1 (IL‐1) have led to better treatment options. This review focuses on a promising new medication, canakinumab, which is a recombinant, human anti‐human‐IL‐1β monoclonal antibody that has been effective in treating adult and pediatric CAPS. Drug Dev Res 72:553–560, 2011.

Inhibition of Spleen Tyrosine Kinase for Rheumatoid Arthritis

Introduction: Spleen tyrosine kinase (Syk) is an important mediator of immunoreceptor signaling in macrophages, neutrophils, mast cells, and B cells. It is found on the synovium of rheumatoid arthritis (RA) patients, suggesting a role for Syk inhibition in the treatment of RA. In an earlier study, the Syk inhibitor R788 was administered for 12 weeks to a refractory RA population not responsive to methotrexate (MTX). Significant reductions in arthritis and serum levels of interleukin-6 were observed in those who received R788 as compared with placebo [1].

Cost-Effectiveness of Biologics Compared with Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis

Introduction: For many rheumatoid arthritis (RA) patients, RA leads to pain and stiffness, progressive joint destruction, functional disability, and premature mortality. The economic burden of RA is significant and includes direct costs (medical visits, medications, laboratory testing, and imaging) and indirect costs (lost productivity, early mortality, and out-ofpocket health care expenses). Disease-modifying antirheumatic drugs (DMARDs) slow the progression of joint damage and loss of function associated with RA. Newer but significantly more expensive biologic agents offer greater potential to slow disease progression and extend productivity, which raises the question of whether the improved clinical outcomes with biologics are worth their higher costs. Aims: This study identified and critically appraised existing economic evaluations of biologics versus DMARDs for adults with RA. Furthermore, it examined whether the incremental cost-effectiveness ratios (ICERs) were within the range of generally accepted medical interventions.