Incidence of Malignancies in a Cohort of Psoriatic Arthritis Patients Taking Traditional Disease Modifying Antirheumatic Drug and Tumor Necrosis Factor Inhibitor Therapy: An Observational Study.

OBJECTIVE: Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. As suggested in 2012 by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), studies devoted to assess cancer in the PsA population are still limited and need to be increased. Therefore, the aim of this study was to determine the incidence of malignancies in patients with PsA who are taking conventional and biologic therapies. METHODS: A cohort of patients with PsA was followed prospectively. At first visit, as well as at each 3-4 month followup visit, according to standardized clinical practice, medical history, and physical and laboratory findings were recorded. Information on the presence of comorbidities, as well as malignancies, was collected. At each visit, data were recorded on radiography and pathology, confirming malignancy diagnosis, when present. RESULTS: A total of 618 patients with PsA were included in the study. In particular, 296 were taking anti-tumor necrosis factor-α (anti-TNF) agents and 322 were taking disease-modifying antirheumatic drugs (DMARD). During the observation period, in the total group, 44 patients (7.1%) had a diagnosis of malignancy. Of them, 14 (4.7%; 95% CI 2.8-7.8; 0.52/100 patient-yrs) received anti-TNF therapy and 30 (9.3%; 95% CI 6.6-13.0; 1.03/100 patient-yrs) received traditional DMARD (p = 0.019). However, after adjusting for major demographic and clinical characteristics, the difference between the 2 treatments was no longer significant (p = 0.480), and the only predictor of malignancy occurrence was age (HR 1.04, 95% CI 1.009-1.073, p = 0.012). CONCLUSION: Data from this study confirm that biological therapies do not lead to any increased risk for cancer development, when adequately administered and with proper followup.

Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

OBJECTIVES: To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). METHODS: This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. RESULTS: All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. CONCLUSIONS: The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Emerging drugs for psoriatic arthritis.

INTRODUCTION: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. AREAS COVERED: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. EXPERT OPINION: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated.

Calcium and vitamin D intakes in children: a randomized controlled trial.

BACKGROUND: Calcium (Ca(2+)) and vitamin D (VitD) play an important role in child health. We evaluated the daily intake of Ca(2+) and VitD in healthy children. Moreover, we demonstrate the efficacy of Ca(2+) and VitD supplementation. METHODS: Daily Ca(2+) and VitD intake was evaluated in consecutive healthy children through a validated questionnaire. Subjects with <70% of dietary reference intakes (DRIs) of Ca(2+) and VitD were invited to participate in a prospective randomized trial with 2 groups of nutritional intervention: Group 1, dietary counseling aiming to optimize daily Ca(2+) and VitD intake plus administration of a commercially available Ca(2+) and VitD supplementation product; Group 2, dietary counseling alone. At the enrollment (T0) and after 4 months (T1) serum 25(OH) Vitamin D levels were assessed. RESULTS: We evaluated 150 healthy children (male 50%, mean age 10 years); at baseline a low VitD intake was observed in all subjects (median 0.79 µg/die, IQR 1.78; range 0.01-5.02); this condition was associated with Ca(2+) intake <70% of the DRIs in 82 subjects (55%). At baseline serum 25(OH)D levels were low (<30 ng/ml) in all study subjects and after 4 months of nutritional intervention, a normalization of serum 25(OH)D levels (≥30 ng/ml) was observed in all children in Group 1 and in only one subject in Group 2 [Group 1: T1 33.8 ng/ml (IQR 2.5) vs Group 2: T1 24.5 ng/ml (IQR 5.2), p <0.001]. CONCLUSIONS: Adequate Ca(2+) and VitD intakes are difficult to obtain through dietary counseling alone in pediatric subjects. Oral supplementation with of Ca(2+) and VitD is a reliable strategy to prevent this condition. TRIAL REGISTRATION: The study was registered in Clinical Trials Protocol Registration System (ID number: NCT01638494).

Determinants and effects of vitamin D supplementation on serum 25-hydroxy-vitamin D levels in patients with rheumatoid arthritis.

OBJECTIVES: Osteoporosis (OP) and increased risk of fracture are relevant features in patients with rheumatoid arthritis (RA). Low levels of serum vitamin D are frequently reported and correlate with a higher RA activity. This study evaluated factors related with the prescription of vitamin D supplements in RA patients and variables influencing the achievement of adequate vitamin D levels. METHODS: Study population was made up by 1168 consecutive RA patients from 22 Italian rheumatology centers. Demographic and clinical variables data were collected and 25OH serum vitamin D was measured in all patients. Insufficient serum 25OH vitamin D levels were defined as values lower than 20 ng/mL. RESULTS: The majority of patients (56.0%) was not taking vitamin D supplements. Among the 514 supplemented patients, 196 (38.1%) were taking insufficient dosages (≤440 IU/day). Variables related with the prescription of supplements were older age, female sex, previous bone density assessment and OP diagnosis. Among the 318 patients using daily supplements ≥800 IU, 88 patients (27.7%) did not reach adequate levels of vitamin D. In these patients a higher HAQ score (OR for 1 point=1.62, 95% CI: 1.06-2.49; p=0.03) and poor sun exposure (OR=2.38, 95% CI: 1.05-5.55; p=0.04) were predictors of vitamin D insufficiency. CONCLUSIONS: Vitamin D deficiency is common in patients with RA, even in patients who are regularly using supplements. Vitamin D supplementation is often ineffective even at the recommended dose of 800 IU/day in more disabled patients.

The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: results of a pilot randomised 6-month trial with methotrexate.

Thirty-five patients with Early Psoriatic Arthritis (EPA) (17 female and 18 male; mean age 25.6 years) entered this randomised 6-month study. At the enrolment, all patients were on non-steroidal anti-inflammatory drug (NSAID) therapy on demand and were divided in two matched groups (A and B). Group A continued NSAID therapy at full dosage in the following 3 months and then added methotrexate (MTX) for another 3 months. Group B was under the combination of NSAID and MTX for the entire 6-month period. Clinical and laboratory assessment included the count of tender joints and/or entheses (TJC), the count of swollen joints and/or entheses (SJC), patient's global assessment (PGA), physician's global assessment (PhGA), patient's assessment of pain (VAS), erythrocyte sedimentation rate (ESR) and serum concentration of C-reactive protein (CRP). All variables were done at baseline (T0), at 3 (T3) and at 6 months (T6). In both group A and in group B, there was a significant improvement of all variables at T3 and T6. However, in comparison to the patients of group A, patients included in group B showed a more rapid and marked improvement of TJC and SJC, which was statistically significant at T3 (p < 0.05). In contrast, the improvement of PGA, PhGA, VAS, ESR and CRP was not significantly different between groups. The early use of MTX in EPA patients markedly improves TJC and SJC. In fact, at T3, other markers used to quantify EPA disease activity, in particular PGA, PhGA, VAS, ESR and CRP, did not show significant differences in EPA patients treated with either NSAIDs or MTX. This finding suggests an incomplete control under MTX of the pathogenetic process and stimulates further interest on early use of other therapeutical approaches capable of modifying the course of disease.

Long-lasting bone damage detected by dual-energy x-ray absorptiometry, phalangeal osteosonogrammetry, and in vitro growth of marrow stromal cells after allogeneic stem cell transplantation.

Bone complications after allogeneic stem cell transplant (allo-SCT) include osteoporosis, fractures, and osteonecrosis. We investigated bone abnormalities in long-term survivors after busulfan cyclophosphamide-conditioning regimen, followed by human leukocyte antigen-identical sibling SCT. Bone density was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN) and phalangeal osteosonogrammetry (OSG) in 41 patients 1-10 yr after allo-SCT. Using colony-forming units-fibroblast (CFU-F) assay, we analyzed the repopulating capacity of clonogenic fibroblast progenitors belonging to the osteogenic stromal lineage. LS and FN bone mineral density (BMD) and phalangeal densitometric values were significantly reduced, compared with 188 healthy controls (P < 0.001). Decrease in T-score less than 1 SD was documented in 29% and 52% of patients at the LS and FN, respectively. OSG detected densitometric values with a T-score less than 1 SD in 68% of transplanted patients. The patients examined within the first 3 yr after transplant showed low BMD, which remained stable at FN and improved at LS. Phalangeal densitometry was low up to 10 yr after transplant. CFU-F was found permanently depressed and unable to give rise to a confluent stroma. Low serum osteocalcin levels were present throughout the whole follow-up period. A significant correlation was found between densitometric values detected by both techniques and CFU-F growth in vitro. Osteonecrosis was associated with lower FN BMD, and phalangeal densitometry correlated inversely with duration of amenorrhea and chronic graft vs. host disease requiring long-lasting steroid therapy. In conclusion, dual-energy x-ray absorptiometry and phalangeal OSG may provide complementary information on bone density after allo-SCT. Prolonged severe impairment of femoral BMD and phalangeal densitometry suggest that bone loss may persist for many years after transplant. Inability to regenerate a normal number of osteoblastic precursors in the stromal stem cell compartment may in part account for severe long-lasting posttransplant decrease in bone mass.