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.

Dramatic response to infliximab in refractory neurosarcoidosis.

Sarcoidosis is a systemic disease characterized by noncaseating granulomas in the involved organs. Neurologic manifestations involving the central and/or peripheral nervous system occur in about 5% of patients. Neurosarcoidosis is often refractory to conventional treatment and therefore more effective treatment options are needed. While the etiology of the disease is still unknown, there is now a better understanding of its pathogenesis on a molecular level. It is clear that tumor necrosis factor-α (TNFα) plays a pivotal role in the development of the granulomas and it is believed to be a key cytokine involved in the pathogenesis of the disease. Taking advantage of this better understanding of disease pathogenesis, anti-TNFα agents are being increasingly used to treat refractory sarcoidosis. We report a patient with refractory neurosarcoidosis who showed dramatic improvement in the clinical and radiological manifestations following treatment with infliximab; he suffered a relapse upon discontinuation of the medication.

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.

BACKGROUND: The 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). METHODS: This 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. RESULTS: There 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 MTX's impact on pregnancy and fertility. CONCLUSIONS: MTX 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 family's understanding of their child's medications.

Pediatric pigmented villonodular synovitis mimicking a septic hip.

We describe a child with pigmented villonodular synovitis initially treated for a presumed hip infection. The correct diagnosis was not made until 2(1/2) years later on a second admission. This is a rare disease with vague presenting symptoms that requires a high index of suspicion. Magnetic resonance imaging and tissue biopsy are usually needed for a definitive diagnosis. Surgery is the primary treatment option; however, the patient described was unusual in that she did well to date with conservative measures.

Rituximab for severe refractory pediatric Wegener granulomatosis.

We describe a case of pediatric Wegener granulomatosis initially treated with cyclophosphamide and oral corticosteroids resulting in remission for 5 years. Of note in this case is relapse with severe pulmonary disease treated with multiple regimens, all unsuccessful. Patient achieved remission with rituximab infusion therapy. This demonstrates how rituximab may be beneficial for childhood-onset Wegener granulomatosis unresponsive to conventional therapy. The case is followed by a review of the current treatment options.

Prophylactic antibiotic usage for Pneumocystis jirovecii pneumonia in patients with systemic lupus erythematosus on cyclophosphamide: a survey of US rheumatologists and the review of literature.

BACKGROUND: Use of cyclophosphamide in systemic lupus erythematosus (SLE) is associated with Pneumocystis jirovecii pneumonia (PJP) that has substantial morbidity and mortality. However, the frequency of PJP in these patients is unknown and there are no guidelines for prophylactic antibiotics. OBJECTIVES: The objectives of this study are to evaluate the frequency of PJP and the need for prophylactic antibiotics in these patients. METHODS: We estimated incidence of PJP and use of prophylactic trimethoprim-sulfamethoxazole in these patients by a literature search and an e-mail survey of US rheumatologists. RESULTS: We identified 18 manuscripts dealing with infections in SLE patients treated with cyclophosphamide. In these manuscripts, 121 cases of PJP were identified in 76,156 SLE patients with a frequency of 15.88 per 10,000 patients.Of 264 rheumatologists surveyed, 133 (50.37%) were using prophylactic antibiotics in these patients. One hundred thirty-one (49.63%) respondents did not use prophylactic antibiotics. 5,174 SLE patients received cyclophosphamide in last 5 years with 19.6 +/- 30.6 (mean +/- SD) patients per rheumatologist. 32 cases of PJP were reported. The total cumulative experience of 264 rheumatologists was 4742 years [(17.96 +/- 10.35) (mean +/- SD)] with a PJP rate of 67.48 per 10,000 years of practice. CONCLUSIONS: The frequency of PJP in SLE patients on cyclophosphamide remains low (0.1588%). Therefore, routine use of trimethoprim-sulfamethoxazole for PJP prophylaxis in SLE patients on cyclophosphamide does not appear to be substantiated by this study, except in those with elevated risk, ie, with severe leucopenia, lymphopenia, high dose corticosteroids, hypocomplementemia, active renal disease, and higher mean SLEDAI score. There is a need for consensus guidelines addressing prophylactic antibiotics in these patients.