ObjectiveThis report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA).MethodsIn this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0–16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16–48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety.ResultsAmong 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA.ConclusionAlthough the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred.Clinical Trial RegistrationNCT01230827; Results.

BackgroundJuvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA.MethodsThis Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013–December 2015. Patients were allocated to one of three age-based cohorts: Cohort 1, 12 to < 18 years; Cohort 2, 6 to < 12 years; and Cohort 3, 2 to < 6 years. Tofacitinib was administered according to age and body weight as tablets or oral solution (grape flavor). PK were assessed on Day 5; safety was assessed at screening, Day 1, and Day 5. Taste acceptability of the oral solution was evaluated.ResultsTwenty-six patients (age range 2–17 years) were enrolled: Cohort 1, N = 8; Cohort 2, N = 9; Cohort 3, N = 9; median tofacitinib doses were 5.0, 2.5, and 3.0 mg BID, respectively. The higher median tofacitinib dose in Cohort 3 versus Cohort 2 reflected implementation of an amended dosing scheme following an interim PK analysis after Cohort 2 recruitment. Geometric mean AUC at steady state (AUCtau) was 156.6 ng•h/mL in Cohort 1, 118.8 ng•h/mL in Cohort 2, and 142.5 ng•h/mL in Cohort 3; Cmax (ng/mL) was 47.0, 41.7, and 66.2, respectively. Ctrough, Cmin, and t1/2 were similar in Cohorts 2 and 3, but higher in Cohort 1. Median time to Cmax (Tmax) was similar between cohorts. Apparent clearance and volume of distribution decreased with decreasing age. Tofacitinib was well tolerated, with no serious adverse events or discontinuations due to adverse events reported. Taste acceptability was confirmed.ConclusionsPK findings from this study in children with polyarticular course JIA established dosing regimens and acceptable taste for use in subsequent studies within the tofacitinib pediatric development program.Trial registrationClinicalTrials.gov: NCT01513902.Electronic supplementary materialThe online version of this article (10.1186/s12969-017-0212-y) contains supplementary material, which is available to authorized users.

Within the last 30 years, the human immunodeficiency virus (HIV) infection has changed its status from inevitably fatal to chronic disorder with limited impact on life span. However, this breakthrough was mainly the effect of introduction of the aggressive antiviral treatment, which has led to the clinically significant increase in CD4+ cell count, resulting in fewer cases of the acquired immunodeficiency syndrome (AIDS) and improved management of opportunistic infections occurring in the course of the disease. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. In 2002, four stages of autoimmunity were proposed in patients infected by HIV, based on the absolute CD4+ cell count, feature of AIDS as well as on the presence of autoimmune diseases. Spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves' disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias). This paper contains the state of art on possible coincidences between HIV infection and a differential types of autoimmune diseases, including the potential mechanisms of this phenomenon. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.

In autoimmune inflammatory diseases, including juvenile idiopathic arthritis (JIA), which leads to joint destruction, there is an imbalance between production of reactive oxygen species (ROS) and their neutralization which, as a consequence, leads to “oxidative stress.” The aim of the study was to assess the concentration of oxidative stress markers: nitric oxide (NO), a degree of lipid membrane damage, and total antioxidant plasma capacity in children with JIA. Thirty-four children with JIA were included into the study. A degree of lipid membrane damage (lipid peroxidation products) was estimated as thiobarbituric acid-reactive substances (TBARs), NO concentration as NO end-products: nitrite/nitrate (NO2−/NO3−) and total antioxidant plasma capacity as ferric reducing ability of plasma (FRAP). NO2−/NO3− serum concentration in children with JIA was statistically significantly higher than that in healthy children (p = 0.00069). There was no significant difference in TBAR levels between children with JIA and the control group. FRAP in sera of children with JIA was lower than that in healthy children, but the difference was not statistically significant. A statistically significant positive correlation was observed between NO end products and the 27-joint juvenile arthritis disease activity score (JADAS-27) and ESR, and a negative correlation was observed between FRAP and C-reactive protein (CRP) and white blood cell count (WBC). Our results confirm the increased oxidative stress in children with JIA. Overproduction of NO and decrease in the antioxidant plasma capacity may be involved in JIA pathogenesis.

Objective.The aim of the study was to investigate whether determination of anticitrullinated protein antibodies (ACPA) provides predictive information on severity of disease course and joint destruction in children with juvenile idiopathic arthritis (JIA).Methods.Sera from 74 children with JIA were examined for ACPA using the ELISA test. To assess joint destruction, plain radiographs of both hands were scored twice according to the Steinbrocker scale: at the beginning of observation and after 8.9 to 15.2 months (median 11.5 months) of the followup. Correlations between ACPA serum levels and the disease characteristics (type of JIA onset, disease activity, disease duration, radiological status) were investigated.Results.Twenty-six out of 74 examined children with JIA (35.0%) were ACPA-positive [> 5 relative units (RU)/ml]. ACPA were present in all types of JIA onset, including 36.6% of children with early stage JIA (disease duration < 6 months). All of the IgM-rheumatoid factor (RF)-positive children with polyarticular type of JIA onset were simultaneously positive for ACPA. ACPA levels correlated positively with disease activity at the beginning of the study (rho = 0.7196; p < 0.0001) and after followup (rho = 0.2485; p = 0.0486). Disease duration did not significantly affect ACPA serum levels. ACPA levels correlated positively with radiological joint destruction in children with JIA, both at the beginning of the study (rho = 0.4599; p = 0.0004) and after the followup period (rho = 0.5523; p < 0.0001).Conclusion.ACPA were superior to IgM-RF in diagnosing JIA and provided predictive information on severity of disease course and radiological outcome.