In the present study we evaluated how systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus influence the efficacy, safety and retention rate of biological disease-modifying anti-rheumatic drug (bDMARD) treatment in rheumatic musculoskeletal disorders (RMDs). The charts of RMD patients treated with the first-line bDMARD were reviewed, collecting data on safety, efficacy and comorbidities at prescription (baseline, BL), after 6 months (6M) and at last observation on bDMARD (last observation time, LoT). In 383 RMD patients, a higher rate of adverse events at 6M (p = 0.0402) and at LoT (p = 0.0462) was present in dyslipidemic patients. Patients who developed dyslipidemia or SAH during bDMARD treatment had similar results (dyslipidemia p = 0.0007; SAH p = 0.0319) with a longer bDMARD retention as well (dyslipidemia p < 0.0001; SAH p < 0.0001). SAH patients on angiotensin converting enzyme inhibitors (ACEis) or angiotensin-II receptor blockers (ARBs) continued bDMARDs for longer than non-exposed patients (p = 0.001), with higher frequency of drug interruption for long-standing remission rather than inefficacy or adverse reactions (p = 0.0258). Similarly, dyslipidemic patients on statins had a better bDMARD retention than not-exposed patients (p = 0.0420). In conclusion, SAH and dyslipidemia may be associated with higher frequency of adverse events but a better drug retention of first-line bDMARD in RMDs, suggesting an additional effect of ACEis/ARBs or statins on the inflammatory process and supporting their use in RMD bDMARD patients with SAH/dyslipidemia.

Immune response to tuberculosis (TB) has been extensively studied in the past decades and classically involves cellular immunity. However, evidence suggests that humoral immunity may play a relevant role. Past studies regarding serum immunoglobulin (Ig) levels in TB are dated and only involve adult subjects. In this study, we retrospectively studied a cohort of 256 children with TB disease and analyzed 111 patients screened for total serum Ig at diagnosis. According to the severity and extent of organ involvement, subjects were divided into four groups, namely, uncomplicated pulmonary TB (UCPTB, 56.3% of patients), complicated pulmonary TB (CPTB, 22.5%), lymph node extrapulmonary TB (LN-EPTB, 7.2%), and extra-nodal extrapulmonary TB (EN-EPTB, 13.5%). Serum IgG and IgA levels were significantly higher in more severe and extended TB disease. Median IgG levels progressively increased from uncomplicated to complicated pulmonary and nodal forms, reaching their highest values in diffuse extra-pulmonary TB. In parallel, UCPTB showed significantly lower frequencies of patients presenting a substantial increase in IgG levels when compared with the other three groups. No relevant differences in IgM levels were detected. Ig screening at follow-up showed a significant reduction in IgG and IgA levels. Finally, we unveiled three cases of selective IgA and one case of selective IgM deficiencies (SIgMD), the latter with a severe clinical course. Serum IgG and IgA may be a useful clinical tool to assess the severity and monitor the treatment response in pediatric TB disease. Moreover, immunological workup in children with TB disease may unmask primary defects of humoral immunity.

Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.

Background:bDMARDs have an effect on glucose homeostasis (1), lipoproteins profile (2; 3) and blood pressure (4). However, with the exception of obesity (5; 6), there are no clear data on how bDMARDs work in patients who already have or develop metabolic comorbidities and whether these conditions can impact on their efficacy and safety profile.Objectives:to evaluate, in chronic inflammatory joint diseases, the effect of arterial hypertension (AH), dyslipidemia (DYS) and diabetes mellitus (DM) on efficacy, safety and retention rate of first-line bDMARDs therapy.Methods:a retrospective observational study on the clinical charts of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Ankylosing Spondylitis (AS), treated with first on-label bDMARD was performed. Data on adverse events, efficacy and comorbidities at the baseline visit in which the bDMARD was prescribed (BL), the visit performed after 6 months of therapy (6M), and the last visit on treatment (LoT) were collected.Results:383 patients (41,8% RA, 33,4% PsA and 24,8% AS) were included in the study, with the predominance of females (F: 67,36%, M: 32,64%; mean age 51,67 ± 15,11 years). Our data show that the presence of comorbidities had no influence on efficacy of bDMARD, while patients who had DYS at BL manifested a higher rate of systemic adverse events either in the first 6 months of therapy (58,9% vs 43,7%, p=0,040) and also later on (80,36% vs. 66,67%, p=0,046). In addition, patients who developed DYS and AH after the 6M visit reported a higher rate of systemic adverse events at LoT visit, compared to others (DYS: 97,8% vs 66,7%, p<0,001; AH: 86,9% vs 65,2%, p=0,031). For what concerns the retention rate, patients who developed DYS or AH during bDMARD treatment continued the drug for a longer period of time (DYS 95,5 vs 19,6 months, p<0,001; AH 72,1 vs 23,4 months, p<0,001). In particular, patients with AH who concomitantly carried out therapy with ACE-inhibitors (ACEi) and/or angiotensin II receptor blockers (ARB) continued bDMARDs for nearly 20 more months than patients who were not exposed to these drugs (40,5 vs 23,4 months, p=0,001) and more frequently maintained the bDMARDS at LoT (59,42% vs. 47,53%). In case of withdrawal in the ACEi/ARB exposed cohort, this was due to well-being and disease remission rather than inefficacy or adverse reaction (p=0,025). In dyslipidemic patients treated with statins, data showed that bDMARDs were continued for a longer time than in DYS patients treated with other anti dyslipidemic therapies (41,09 vs. 26,50 months, p=0,042).Conclusion:our data suggest that AH and DYS may be associated with higher frequency of adverse events but a better drug retention. The combination of bDMARD and ACEi/ARB may determine a better control of the inflammatory process by inhibition of angiotensin II, favouring the achievement of remission. In AH patients on bDMARDs, ACEi and ARB could therefore represent an useful anti-hypertensive drug choice. Similarly, statins could be the treatment of choice in DYS patients.References:[1]Gonzalez-Gay MA, et al. Clin Exp Rheumatol. 2006.[2]Pollono EN, et al. Clin Rheumatol. 2010[3]van Sijl AM, et al. Semin Arthritis Rheum. 2011.[4]Yoshida S, et al. J Hum Hypertens. 2014.[5]Gremese E, et al. Arthritis Care Res (Hoboken). 2013.[6]Heimans L, et al. Arthritis Care Res (Hoboken). 2013.Disclosure of Interests:Laura Cometi: None declared, Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Nicolò Chiti: None declared, Lorenzo Tofani: None declared, Francesca Nacci: None declared, Francesca Bartoli: None declared, Silvia Bellando Randone: None declared, Ginevra Fiori: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim