BackgroundBiologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA). One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA). The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA) IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL) in patients affected by RA in maintaining LDA or remission obtained after biological therapy.MethodThis is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28), clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs) therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months.ResultsThe rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups.ConclusionThis is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA cytokines may be an opportunity to explore in the management of RA.

Rheumatic diseases are traditionally treated using symptomatic drugs (NSAIDs -Nonsteroidal Anti-Inflammatory Drugs) and specific drugs. Nevertheless, the inhibitory effect of traditional NSAIDs, caused by both types of COX enzymes, besides easing inflammation and pain, also has a number of damaging effects on gastric mucosa protection mechanisms. Therefore, NSAIDs administration is also contraindicated in patients who suffered or are suffering from chronic liver or kidney disease, or in patients on anticoagulants.We therefore decided to study the effect of a combination of fixed doses of Serratiopeptidases, Bromelain and Methylsulfonylmethane extracts in inflammatory joint diseases. From 1 st December 2014 to 31 st March 2015, we selected 74 patients with chronic inflammatory joint diseases of different types in an acute phase, as documented by high VAS (Visual Analogue Scale) rates and increased ESR and CRP values. Patients were randomly subdivided in two groups: in treatment group, during the first 3 months, patients also took a solution of Serratiopeptidases, Bromelain and Methylsulfonylmethane extracts, before the main meal of the day; in control group patients did not take any therapy in addition to the background one.Patients in the treatment group showed a statistically significant reduction in ESR and pain, measured with the VAS scale; moreover intake of Serratiopeptidases, Bromelain and Methylsulfonylmethane extracts led to no statistically significant change in liver (AST and ALT) and kidney (Creatinine) function in the treatment group as opposed to the control one.In this preliminary study, the product containing Serratiopeptidases, Bromelain and Methylsulfonylmethane extracts achieved optimum effectiveness and showed no side effects, although a long-term multi-centre study would be needed to confirm our results.

BackgroundMethotrexate (MTX) is the DMARD of first choice in the treatment of rheumatoid arthritis (RA).ObjectivesTo investigate the clinical characteristics and describe therapeutic approaches in RA patients ongoing MTX not achieving a DAS28 “low disease activity” score.MethodsThis is a case-control analysis including 186 patients (mean age±SD, 61±12 years, 16% males) who did not achieve a DAS28 “low disease activity” score (defined by a value ≤3.2) and 558 age- and gender-frequency-matched (1:3), randomly selected controls (mean age age±SD, 61±13 years) who achieved a DAS28 “low disease activity” from the original cohort investigated in the MARI study. The MARI study enrolled RA patients on treatment for at least 12-month with MTX. Demographic, clinical, laboratory and pharmacological characteristics of patients recorded at baseline visit were considered for the current analysis. We first compared the characteristics of patients who reached the endpoint with those of subjects who did not by univariate analyses, thereafter, we performed a multivariate model to identify predictors of not achieving the endpoint. We further investigated the therapeutic approaches in patients not achieving the endpoint.ResultsCompared to patients with a DAS28 ≤3.2, subjects not achieving the endpoint presented with a significant higher (mean±SD) weight and BMI (DAS28 ≤3.2: 25±4 versus DAS28 >3.2: 26±5, P=.022), and longer duration of symptoms (months±SD) before the RA diagnosis (11±15 versus 15±20, P=.009). A higher proportion of subjects within the group not achieving the endpoint presented with polyarticular disease (DAS28 ≤3.2: 57% versus DAS28 >3.2: 96%, P<.001), erosive arthritis (49% versus 73%, P<.001), extra-articular symptoms (3% versus 10%, P<.001), positive RF test (63% versus 73%, P=.013), and increased CRP (13% versus 53%, P<.001). The proportion of patients treated with oral MTX was 25% in the subgroup with DAS28 ≤3.2 and 15% in the subgroup with DAS28 >3.2 (P=.004). In the logistic regression analysis, the variables predictive of a DAS28 >3.2 were polyarticular disease (OR 4.0, 95% CI 2.4–6.7, P<.001), erosive arthritis (OR 2.2, 95% CI 1.4–3.4, P<.001), and increased CRP (OR 7.4, 95% CI 4.9–11.4, P<.001). In patients who did not reach the endpoint, the main therapeutic strategies were: a change in the route of administration of MTX (DAS28 >3.2: 13% versus DAS28 ≤3.2: 4%, P<.001) in favor of subcutaneous MTX, an increase of the dose of MTX (13% versus 2%, P<.001), and the prescription of a new biologic (12% versus 1%, P<.001).ConclusionsOur results identified a number of variables potentially associated the risk of not achieving a DAS28 “low disease activity” score in RA patients ongoing MTX treatment. Longitudinal studies are warranted.Disclosure of InterestNone declared

Purpose: In order to further elucidate the efficacy and safety of some nutritional supplements on gonarthrosis, we have conducted a preliminary randomized multicenter (n=9) observational study comparing the effects of an association of Fortigel®(10gr) and Fucoidan (100mg) (ACTEN®) versus another commonly therapeutically used formulation based on Glucosamine (500mg), Chondroitin Sulfate (400mg) hyaluronic Acid (50 mg) and Vitamin C (100 mg) (COMBIART). Patients and Methods: The protocol was administered over a 12-weeks period in a population (n=126) aged 40-65 years, with diagnosed mild-tomoderate Osteoarthritis (OA) of the knee (grade 2-3 of Kellgren Lawrence grading scale).Safety was measured by closely monitoring adverse events. Efficacy was measured by grading evaluations, at basal, 1 month and 3 months controls, of the Visual Analog Scale (VAS) and the Lequesnealgo functional index for severity of osteoarthritis (LAI) for particular functionality. Results: Both groups showed an important reduction (P<0.0001) in the mean visual analog scale values at T1 (28.5% ACTEN®, 21.3% COMBIART at1 month) and T3 (49.4% ACTEN®, 40.1% COMBIART at 3 months), as well as a marked reduction in the Lequesnealgo functional index means (P<0.0001) (ACTEN® 28.9% T1 44.9% T3, COMBIART T1 21.3% T3 37%). The effect seems to be time dependent, as the mean values decrease further for both parameters from T1 to T2 (P<0.0001, for VAS for both groups; P 0.0011 for ACTEN® group, P 0.0064 Control group for LAI). No statistically significant difference was found between the ACTEN® group and the COMBIART group at time T1 or T3. These interesting preliminary data will be further investigated on a larger scale. Conclusions: Fortigel®(10gr) and Fucoidan (100 mg) (ACTEN®) taken as oral nutritional supplements have a significant impact as therapeutic intervention for knee osteoarthritis as indicated by the marked decrease in VAS and LAI values over the course of the treatment. A similar effect, as expected, has been confirmed in the COMBIART group, and no statistically significant difference has been detected between the two groups.

Purpose: In order to further elucidate the efficacy and safety of some nutritional supplements on gonarthrosis, we have conducted a preliminary randomized multicenter (n=9) observational study comparing the effects of an association of Fortigel® (10 gr) and Fucoidan (100 mg) (ACTEN®) versus another commonly therapeutically used formulation based on Glucosamine (500 mg), Chondroitin Sulfate (400mg) hyaluronic Acid (50 mg) and Vitamin C (100 mg) (COMBIART). Patients and methods:The protocol was administered over a 12-weeks period in a population (n=126) aged 40-65 years, with diagnosed mild-to-moderate osteoarthritis (OA) of the knee (grade 2-3 of Kellgren Lawrence grading scale). Safety was measured by closely monitoring adverse events. Efficacy was measured by grading evaluations, at basal, 1 month and 3 months controls, of the Visual Analog Scale (VAS) and the Lequesne algofunctional index for severity of osteoarthritis (LAI) for articular functionality.Results: Both groups showed an important reduction (P < 0.0001) in the mean visual analog scale values at T1 (28.5% ACTEN®, 21.3% COMBIART at 1 month) and T3 (49.4% ACTEN®, 40.1% COMBIART at 3 months), as well as a marked reduction in the Lequesne algofunctional index means (P < 0.0001) (ACTEN® 28.9% T1 44.9% T3, COMBIART T1 21.3% T3 37%). The effect seems to be time dependent, as the mean values decrease further for both parameters from T1 to T2 (P < 0.0001, for VAS for both groups; P 0.0011 for ACTEN® group, P 0.0064 Control group for LAI). No statistically significant difference was found between the ACTEN® group and the COMBIART group at time T1 or T3. These interesting preliminary data will be further investigated on a larger scale.Conclusions: Fortigel® (10gr) and Fucoidan (100 mg) (ACTEN®) taken as oral nutritional supplements have a significant impact as therapeutic intervention for knee osteoarthritis as indicated by the marked decrease in VAS and LAI values over the course of the treatment. A similar effect, as expected, has been confirmed in the COMBIART group, and no statistically significant difference has been detected between the two groups.