Critical appraisal of canakinumab in the treatment of adults and children with cryopyrin-associated periodic syndrome (CAPS)

The cryopyrin-associated syndromes (CAPS) include three autosomal-dominant syndromes, that are caused by a mutation in the NLRP3 gene on chromosome 1, encoding the cryopyrin protein. These syndromes, familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset multisystem inflammatory disease, are characterized by urticaria-like rash, fever, central nervous system inflammation, an arthropathy and a risk of the development of amyloidosis in a respectively escalating degree of severity between the various syndromes. Recently the role of cryopyrin in the regulation of interleukin (IL)-1 production and activation was described and anti IL-1 therapies were found to be very effective in treating these syndromes. There are several types of anti IL-1 medications based on different mechanisms of antagonizing IL-1. This paper focuses on the efficacy and safety of canakinumab, a long-acting humanized anti IL-1 antibody, in treating these syndromes

Abatacept in the treatment of polyarticular JIA: development, clinical utility, and place in therapy

Juvenile idiopathic arthritis (JIA) is a group of chronic arthritides affecting children. The polyarthritis category, affecting five or more joints in the first six months, tends to be more aggressive, leading to a destructive joint disease with significant morbidity, disability, and costs to society. The current treatment regimen, which primarily combines methotrexate and tumor necrosis factor alpha (TNF-α) blockade, still leaves a significant group of patients with an inadequate response. Therefore, the development of new medications that act via other mechanisms of pathogenesis is necessary. T cell lymphocytes are key components in the immune reaction in JIA. Cytotoxic lymphocyte-associated antigen-4 (CTLA-4) is a potent inhibitor of the costimulation pathway necessary to activate T cells. Abatacept is a recombinant fusion protein comprising the extracellular part of human CTLA-4 connected to a modified Fc part of IgG-1. In a randomized, multinational, blinded withdrawal study in children with polyarticular JIA, abatacept was found to be effective in about 70% of the patients, including 39% of TNF-α blockade failures, with significantly fewer flares occurring during the withdrawal phase than in patients receiving placebo. Abatacept continued to show good efficacy in a three-year open-label extension study, with a beneficial effect on health-related quality of life. The safety profile of abatacept is generally good. In 2008, the US Food and Drug Administration approved abatacept for use in children over six years of age with JIA and a polyarticular course. In 2010, the European Medicines Agency gave approval for abatacept to be used in combination with methotrexate for those who fail at least one disease-modifying medication and TNF-α blockade

Nitrous Oxide sedation for intra-articular injection in juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>Intra-articular corticosteroid injection in juvenile idiopathic arthritis (JIA) is often associated with anxiety and pain. Recent reports advocate the use of nitrous oxide (NO), a volatile gas with analgesic, anxiolytic and sedative properties.</p> <p>Objective</p> <p>To prospectively evaluate the effectiveness and safety of NO analgesia for intra-articular corticosteroid injection in JIA, and to assess patients and staff satisfaction with the treatment.</p> <p>Methods</p> <p>NO was administered to JIA patients scheduled for joint injection. The patient, parent, physician and nurse completed visual-analog scores (VAS) (0–10) for pain, and a 5-point satisfaction scale. Change in heart rate (HR) during the procedure was recorded in order to examine physiologic response to pain and stress. Patient's behavior and adverse reactions were recorded.</p> <p>Results</p> <p>54 procedures (72 joints) were performed, 41 females, 13 males; 39 Jewish, 13 Arab; mean age was 12.2 ± 4.7 year. The median VAS pain score for patients, parents, physicians and nurses was 3. The HR increased ≥ 15% in 10 patients. They had higher VAS scores as evaluated by the staff. The median satisfaction level of the parents and staff was 3.0 and 5.0 respectively. Adverse reactions were mild.</p> <p>Conclusion</p> <p>NO provides effective and safe sedation for JIA children undergoing intra-articular injections.</p

Growing pains in children

We review the clinical manifestations of "growing pains", the most common form of episodic childhood musculoskeletal pain. Physicians should be careful to adhere to clear clinical criteria as described in this review before diagnosing a child with growing pain. We expand on current theories on possible causes of growing pains and describe the management of these pains and the generally good outcome in nearly all children

Post-streptococcal reactive arthritis in children: a distinct entity from acute rheumatic fever

There is a debate whether post-streptococcal reactive arthritis (PSRA) is a separate entity or a condition on the spectrum of acute rheumatic fever (ARF). We believe that PSRA is a distinct entity and in this paper we review the substantial differences between PSRA and ARF. We show how the demographic, clinical, genetic and treatment characteristics of PSRA differ from ARF. We review diagnostic criteria and regression formulas that attempt to classify patients with PSRA as opposed to ARF. The important implication of these findings may relate to the issue of prophylactic antibiotics after PSRA. However, future trials will be necessary to conclusively answer that question

JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies

BACKGROUND. Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25 (IQR, 0.1-0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09) to 0.11 mg/kg/day (IQR, 0.02-0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients' quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment