HyalOne® in the treatment of symptomatic hip OA - data from the ANTIAGE register: seven years of observation.

OBJECTIVE: Several studies on knee osteoarthritis suggest that the intra-articular administration of hyaluronic acid products may be a relevant option in the management of patients with persistent pain. The aim of this study is to report the data of efficacy of US-guided HyalOne®/Hyalubrix® 60 injections in a large population of patients with hip osteoarthritis, repeated at least 2 times per year for up to seven years. PATIENTS AND METHODS: This is a prospective, post-marketing, cohort study. Data were collected from the ANTIAGE registry. Values of Lequesne index, pain VAS, NSAIDs intake, global medical and patients assessments were evaluated every six months from the baseline to the end of the follow-up, seven years later. The inclusion criteria were: age ≥18 years, symptomatic hip osteoarthritis of at least 1-year duration, and up to 84 months of follow-up. All the patients received hyaluronic acid injections at least every six months, using ultrasound guidance to ensure accurate placement. RESULTS: 1022 patients were included in the study. The patients were categorized by age classes, gender, and body mass index (BMI). All the groups show a statistically significant reduction at all time points compared to baseline values of Lequesne index, pain VAS, NSAIDs intake, global medical and patients assessments. There are slight differences in the subgroups of overweighted, obese and over 70 years patients. CONCLUSIONS: Our study supports the clinical efficacy and safety of HyalOne®/Hyalubrix®60 in patients affected by osteoarthritis. This is the first study, reporting on a large cohort of patients in different categories with a long follow-up on seven years. The data confirm the proper use of ultrasound-guided viscosupplementation (VS) as background therapy in the management of hip osteoarthritis.

An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis.

BACKGROUND: Biologic 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. METHOD: This 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. RESULTS: The 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. CONCLUSION: This 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.

Differences Regarding Branded HA in Italy, Part 2: Data from Clinical Studies on Knee, Hip, Shoulder, Ankle, Temporomandibular Joint, Vertebral Facets, and Carpometacarpal Joint.

OBJECTIVES: The aim of the current study is to collect scientific data on all branded hyaluronic acid (HA) products in Italy that are in use for intra-articular (IA) injection in osteoarthritis (OA) compared with that reported in the leaflet. METHODS: An extensive literature research was performed for all articles reporting data on the IA use of HA in OA. Selected studies were taken into consideration only if they are related to products based on HAs that are currently marketed in Italy with the specific joint indication for IA use in patients affected by OA. RESULTS: Sixty-two HA products are marketed in Italy: 30 products are indicated for the knee but only 8 were proved with some efficacy; 9 products were effective for the hip but only 6 had hip indication; 7 products proved to be effective for the shoulder but only 3 had the indication; 5 products proved effective for the ankle but only one had the indication; 6 products were effective for the temporomandibular joint but only 2 had the indication; only 2 proved effective for vertebral facet joints but only 1 had the indication; and 5 products proved effective for the carpometacarpal joint but only 2 had the indication. CONCLUSIONS: There are only a few products with some evidences, while the majority of products remain without proof. Clinicians and regulators should request postmarketing studies from pharmaceuticals to corroborate with that reported in the leaflet and to gather more data, allowing the clinicians to choose the adequate product for the patient.

Differences among Branded Hyaluronic Acids in Italy, Part 1: Data from In Vitro and Animal Studies and Instructions for Use.

BACKGROUND: The use of hyaluronic acid (HA) for intra-articular (IA) injection is widespread around the world for patients affected by osteoarthritis. AIM: The aim of this study is to identify scientific evidence from in vitro and in vivo studies supporting the use of IA HAs marketed in Italy. We also evaluated the accuracy of indications and contraindications reported in the leaflets of such HAs compared with the available scientific evidence. MATERIALS AND METHODS: An extensive literature search was performed to identify all in vitro and in vivo model studies reporting on the effects of various HAs marketed in Italy for IA use. Data reported in the leaflets of different HA-based products for IA use were extracted and analyzed alongside evidence from in vitro and in vivo model studies. RESULTS: Nine in vitro studies and 11 studies on animal models were examined. Comparing results with what is reported in the leaflets of HAs marketed in Italy, it was observed that many branded formulations are introduced in the market without any reporting of basic scientific evidence. Only 12.82% and 17.95% of branded products had been shown to be effective with scientific evidence from in vitro and in vivo studies, respectively. The rationale of use of these products is based on their nature, as if a class effect existed such that all HAs would yield similar effects. CONCLUSIONS: Data on HAs deriving from in vitro and in vivo studies are scarce and relate to only a small percentage of products marketed in Italy. Many indications and contraindications are arbitrarily reported in Italian HA leaflets without the support of scientific evidence. Larger and brand-specific studies are necessary and should be reported in the leaflets to guide clinicians in making an appropriate choice regarding HA-based IA therapy.

The discrepancy between recommendations and clinical practice for viscosupplementation in osteoarthritis: mind the gap!

Recently AAOS, ACR and OARSI revised their recommendations for the management of knee osteoarthritis (OA) and for hand, knee and hip joints. During ISIAT (International Symposium on Intra-Articular Treatments) 2013 round table on recommendations about the use of intra-articular Hyaluronic Acid (IAHA) in OA, several considerations were elaborated by the ISIAT Technical Expert Panel (TEP) regarding discrepancy between recommendations and clinical practice. The ISIAT TEP gathered the following eight suggestions regarding the drawing of recommendations on the use of IAHA in OA and its comparison with other treatments. It is necessary to merge data coming from both RCTs and registers. Only studies with a strong level of evidence should be taken into account. A common threshold of efficacy should be assessed for comparing treatments. Evaluation of hard outcomes is essential. The effect size of placebo as comparator should be attentively considered in RCTs. Particular attention should be given to different phenotypes of OA that may possibly respond differently to each treatment. Compliance and long-term side effects of different therapeutic approaches should be evaluated. Pharmacoeconomic evaluation should be performed on the long term.

Duration of symptom relief after intra-articular injection of hyaluronic acid combined with sorbitol (anti-ox-vs) in symptomatic hip osteoarthritis.

The intra-articular administration of hyaluronic acid (HA) in hip osteoarthritis (OA) has been recently increased following the use of ultrasound guidance to perform an accurate delivery of the injected product. Viscosupplementation in hip OA seems to show similar results to those obtained by viscosupplementation in knee OA. However, an unmet need is the duration of symptomatic relief, therefore several new products are proposed to prolong and increase symptomatic effects. Among these, an innovative viscosupplement has been produced from high a concentration of HA combined with a high concentration of sorbitol as a free radical scavenger. The aim of this study is to evaluate the mid-term pain-relief effect of an ultrasound-guided injection of SynolisV-A (ANTI-OX-VS) in patients suffering from symptomatic hip osteoarthritis. Lequesne index, Health Assessment Questionnaire (HAQ), pain reduction, Global Patient Assessment (GPA), Global Medical Assessment (GMA) and reduction in monthly analgesic consumption were assessed during the 12-month follow-up after the injection. A total of 20 patients were enrolled in the study and received one IA US-guided injection of two syringes of ANTI-OX-VS into the target hip. Eleven drop-out patients were registered, of whom 2 were for loss of efficacy at 6 months, 1 for loss of efficacy at 9 months and 8 patients for severe comorbilities. Mean scores of all clinical parameters evaluated at each control visit were significantly different when compared with baseline mean value. No systemic adverse events were observed. Even though the sample size of this study is limited, the results suggest a durable good efficacy of a 4-ml single injection of ANTI-OX-VS in hip OA, at least for the patients who completed the study. A larger number of patients and an RCT are needed to confirm these data, investigating also the predictive factors of clinical response to ANTI-OX-VS.

Radiological outcomes in randomized controlled trials on biologic therapies for rheumatoid arthritis: a narrative review.

Several scores are currently used to estimate the radiologic progression of patients affected by rheumatoid arthritis. Modified Sharp score, Genant-modified Sharp score and van der Heijde-modified Sharp score are actually the most commonly used scores in randomized controlled trials on biologic drugs actually available in scientific literature. An intensive literature search (EMBASE, PubMed, MEDLINE) was performed in order to identify randomized controlled studies reporting on the efficacy of biologic drugs on radiologic progression in rheumatoid arthritis by means of approved scoring methods such as Sharp score variants. All studies were evaluated for their approach to radiologic outcome, and a global evaluation of trends towards radiologic evaluation was performed. Eighteen studies were identified and analyzed, and data from such randomized controlled trials (RCTs) were reported and described regarding their approach to radiologic outcomes. The use of three different scoring methodologies generated similar but non-comparable data; although a big part of the studies reported good efficacy profiles of several biologic drugs on radiologic progression, data from such studies are not comparable as the three different scoring methods are not convertible from one to another. At present, there is no standardization for the evaluation of radiologic outcomes, thus preventing comparison of results obtained by different drugs. The use of a single, standardized and widely approved scoring method would grant the possibility of comparing such data.

Safety of intra-articular hip injection of hyaluronic acid products by ultrasound guidance: an open study from ANTIAGE register.

OBJECTIVE: We developed a standardized technique for ultrasound guided intra-articular injection of the hip joint with the purpose of extending routine intra-articular injection of hyaluronans and steroids to the hip, as commonly used in the knee. In this article we report the safety of this technique in an extended series of patients. PATIENTS AND METHODS: Patients were injected supine with an anterosuperior approach under ultrasound guidance. The Us probe is applied with a target device for biopsy. RESULTS: The standardised technique was used to inject 1906 patients with 4002 injections of hyaluronan products over a four-year period. The treatment was well tolerated with few, and exclusively local, side effects. CONCLUSIONS: The administration of hyaluronans under ultrasound-guided intra-articular injection is a safe technique for treatment of rheumatic diseases of the hip.

May etanercept and PTH (1-34) association heal erosions in early rheumatoid arthritis? A pilot study.

INTRODUCTION: Rheumatoid arthritis (RA) is characterized by the formation in the joints of an inflammatory tissue, which causes the appearance of localized erosions on the margins of the joints. The molecular mechanism that causes the bone erosion is multifactorial. Inflammatory cytokines imbalance and OPG-RANK-L system are involved. OBJECTIVE OF THE STUDY: The aim of the study is to evaluate the possibility of inducing healing or reduction in the number of erosions in Rheumatoid Arthritis patients treated with anti-TNF-alpha adding Teriparatide (PTH1-34) to standard treatment with anti-TNF. PATIENTS AND METHODS: Twenty adult patients with active RA diagnosed according to American Rheumatism Association (ARA) criteria at least 6 months before study begin were enrolled. Only patients affected by established RA (6 to 18 months from symptoms beginning) were recruited. Eligible patients were randomized to receive a standard dosage of etanercept (50 mg/week) or etanercept at same dosage with an addition of teriparatide (20 mg). Evaluation of eventual healing of arthritic erosions by magnetic resonance imaging was performed at time zero and then at twelve months. The following evaluation was assessed at baseline and after 12 months according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) definitions: number of erosion and presence or absence of synovitis, effusion and bone oedema. A comparative examination of quantitative and qualitative assessment of each parameter was applied. Plain radiographs of the hands were obtained at baseline and 52 weeks. Radiographs were scored blindly using the van der Heijde modification of the Sharp method. Safety of each treatment was evaluated by means of the adverse events (AES) evaluation and report. RESULTS: There were no significant differences in baseline characteristics between the groups. The study did not achieve its primary endpoint of healing erosions. In the active arm no healing of erosions was found. At 52 weeks, there were no new MRI erosions in two arms. Bone oedema scores were significantly improved at 52 weeks in favour of both treatments versus baseline scores, without inter-groups differences. X-ray patterns were unchanged in all patients of both groups. No new erosions or previous erosions' healing were observed. No AEs were reported. Patients from both groups demonstrated a significant reduction in the DAS 28 scores at 52 weeks (p < 0.005) if compared with baseline values. CONCLUSIONS: These data confirm rapid control of inflammation and MRI damage benefits after Etanercept administration without a significant improvement in MRI findings after concomitant addition of teriparatide. Even though these results could seem to suggest to avoid the simultaneous use of these two drugs to treat RA erosions, further studies might be suggested to asses if sequential adminstration of an anabolic agent such as Teriparatide, after achieving clinical remission, may be able to improve bone damage.

Socioeconomic burden of total joint arthroplasty for symptomatic hip and knee osteoarthritis in the Italian population: a 5-year analysis based on hospitalization records.

OBJECTIVE: To assess the burden of total joint arthroplasties (TJAs) performed for symptomatic hip and knee osteoarthritis (OA) in the Italian population. METHODS: We analyzed national hospitalizations and diagnosis-related group databases to compute incidence, annual percent change (APC), direct costs, and working days lost between 2001 and 2005 following TJA due to OA. RESULTS: In 2005, we recorded a total of 41,816 (APC +5.4; 95% confidence interval [95% CI] 5.1-5.8) and 44,051 (APC +13.4; 95% CI 13.1-13.8) hip and knee arthroplasties, respectively. Women represented the majority of patients undergoing TJA procedures (female:male ratio 1.7:1 for hip arthroplasties and 2.9:1 for knee arthroplasties). When analyzing the data by age groups, most of the patients were in the age groups 65-74 years and ≥75 years, although the highest increases were observed in those ages <65 years. Revisions accounted for 6,387 (APC +4.9; 95% CI 4.0-5.7) and 2,295 (APC +17.4; 95% CI 15.7-19.2) procedures for the hip and knee, respectively. Loss of working days in patients ages <65 years was estimated between 805,000 and 1 million days. Hospital costs increased from 741 million to 1 billion euros over the 5-year period (from 412 to 538 million euros for hip arthroplasties and from 329 to 517 million euros for knee arthroplasties). Rehabilitation costs increased from 228 to 322 million euros. Postoperative complications were estimated between 3.1 and 4.4 million euros. The average costs per patient were 16,835 and 15,358 euros for hip and knee arthroplasties, respectively. CONCLUSION: The socioeconomic burden of TJAs performed for symptomatic OA in Italy is remarkable and calls for the adoption of proper preventive measures.

Indirect comparison of the effects of anti-TNF biological agents in patients with ankylosing spondylitis by means of a mixed treatment comparison performed on efficacy data from published randomised, controlled trials.

OBJECTIVES: To compare ASAS (Assessment in Ankylosing Spondylitis Response Criteria), 20 response patterns between anti-TNF biological agents in patients with ankylosing spondylitis by means of a mixed treatment comparison of different randomized, controlled trials (RCTs) on the efficacy of biological therapies. METHODS: A systematic review of literature was performed to identify a number of similarly designed double-blind, randomized, placebo-controlled trials investigating the efficacy of the TNF-α inhibitors etanercept, infliximab, and adalimumab in the treatment of ankylosing spondylitis patients, conducted over an 18-year period. The end-point of interest was ASAS20 response criteria at 24 weeks. Results were analyzed simultaneously using Bayesian mixed treatment comparison techniques. Results were expressed as odds ratio (OR) of ASAS20 response and associated 95% credible intervals (CrIs). The probability of being the best treatment was also reported. RESULTS: Three RCTs were selected for data extraction and further analysis. By mean of MTC, all anti-TNF agents demonstrated to be more efficacious in inducing an ASAS20 response than placebo. Infliximab shows a 72% probability of being the best treatment of all. Adalimumab and etanercept show probabilities of 13% and 15%, respectively. No differences were observed when comparing directly an anti-TNF-α agent against another. When compared with placebo, Infliximab increases the probability of response by ∼7-times (OR = 6.8), Adalimumab by ∼4-times (OR = 4.4), and Etanercept by 5-times (OR = 4.9). Differences in trials procedures, the use of a fixed-effect model, and the small number of trials included represent limitations of this study CONCLUSIONS: Even if the mixed treatment comparisons between infliximab, adalimumab, and etanercept did not show a statistically significant difference, this analysis suggests that infliximab, compared to placebo, is expected to provide the highest rate of ASAS20 response in SA patients naive to biologic treatments.

Mixed-treatment comparison of anabolic (teriparatide and PTH 1-84) therapies in women with severe osteoporosis.

PURPOSE: The recent development of compounds with anabolic action on bone have increased the range of therapeutic options for the treatment of osteoporosis and the prevention of fractures. Two major PTH analogs, the synthetic full-length 1-84 PTH molecule and the recombinant 1-34 N-terminal fragment (teriparatide), are available for the treatment of osteoporosis in many countries. There have bee no comparative trials on the bone anabolic effects of these compounds. MATERIALS AND METHODS: In this study we applied a mixed treatment comparison (MTC) to compare the efficacy of teriparatide versus PTH 1-84 for the prevention of vertebral and non-vertebral fractures in women with severe osteoporosis. With this approach the relative treatment effect of one intervention over another can be obtained in the absence of head-to-head comparison. Among the candidate papers selected for analysis, two randomized controlled trials investigating the effects of teriparatide and PTH 1-84 met the selection criteria and underwent MTC analysis. RESULTS: Based on a fixed-effect MTC model analysis of data from two RCTs, teriparatide (20 µg/day) showed a 70% and 94% probability of being the best treatment for the prevention of vertebral and non-vertebral fractures, respectively. Together with a lack of statistical significance, this study has additional limitations. Some differences in trial procedures and populations exist; another limitation concerns the impossibility of carrying out a randomized-effect model MTC, due to sample exiguity. Furthermore, in order to consider unknown or unmeasured differences of covariates across trials, a random-effects approach would be preferred in order to assess the presence of heterogeneity across comparisons. In contrast, in our analysis a fixed-effect MTC model only was used. CONCLUSIONS: Teriparatide is expected to provide a greater efficacy over PTH 1-84 with both vertebral and non-vertebral fracture prevention in postmenopausal women with severe osteoporosis.

The impact of treatment with hylan G-F 20 on progression to total hip arthroplasty in patients with symptomatic hip OA: a retrospective study.

INTRODUCTION: There is scarce data available on intra-articular hyaluronan's ability to modify the progression of osteoarthritis (OA). OBJECTIVE: The purpose of this retrospective pilot study was to assess the impact of treatment with hylan G-F 20 on progression to total hip replacement (THR) in patients with symptomatic hip OA. RESEARCH DESIGN AND METHODS: The records of patients presenting with symptomatic hip OA and treated with hylan G-F 20 were analysed. Endpoints were the number of THRs performed and the survival time (in months) between commencement of treatment and THR, if performed. Endpoints were evaluated for the entire study population and for those sub-groups of patients which were, or were not, defined as candidates for THR prior to intra-articular treatment. Predictive factors of progression to THR were also assessed. RESULTS: A total of 850 patients' records were evaluated and 224 patients' data were included in the study and evaluated. Eighty-four patients (37.5%) progressed to THR, 206 patients (92.0%) achieved 12 months survival, 170 patients (75.9%) achieved 24 months survival, and 69 patients (30.8%) achieved 5 years survival. Mean survival time was 36 months. Classification as a THR candidate, Lequesne score, ultrasound pattern and the presence of diabetes were predictive factors for progression to THR. CONCLUSIONS: These results suggest that hylan G-F 20 could be included in the management of symptomatic hip OA before recommendation for THR, particularly in patients presenting with milder symptoms, or in patients where, due to comorbidities or personal choice, THR is not a feasible option. Limitations of this study include the retrospective study design and the lack of a control group to determine any placebo effect of hylan G-F 20. Further prospective studies are therefore needed to corroborate these results.

A new chance to maintain remission induced by anti-TNF agents in rheumatoid arthritis patients: CYnAR study II of a 12-month follow-up.

The advent of biological therapies represented the beginning of a new era in the therapy of Rheumatoid Arthritis (RA), as demonstrated in several studies, but still many questions about their safety, especially in long term use, and correct administration time remain unanswered. Once remission is achieved, the orientation of clinicians regarding the maintenance of biological therapy or the switch to another immunosuppressive therapy is still uncertain. In our previous study 21 patients affected by RA who reached remission by the use of a combined therapy of anti-TNF drugs and methotrexate (MTX) underwent CyA-MTX combination therapy for maintaining remission state and were evaluated during a 6-month follow-up. The present study aims to investigate these data by a longer follow-up (12 months) and on a larger population. Fifty-three RA patients, with a disease duration of less than 3 years and DAS28<3.2 that reached a level of low disease activity within 6-8 months from the beginning of anti-TNF and methotrexate therapy, were enrolled in the study. By the suspension of anti-TNF therapy, patients underwent A-Cyclosporine (2-3 mg/kg/day) and methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation rate (ESR), C Reactive Protein (CRP) were all tested at time 0 and every 2 months after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and methotrexate therapy, as well as liver and kidney profiles. Side effects were also recorded. Of 53 patients, 50 completed the study with a 12-month follow-up. Twenty-one (42%) patients maintained clinical parameters within low disease activity values at 12 months, while 29 (58%) patients showed an increase in DAS28 and other parameters: 16 (32%) patients at the 6-month control, 13 (26%) patients at the 12-month control. Our data show that 42% of the patients undergoing A-Cyclosporin and Methotrexate therapy maintained low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.

Hip viscosupplementation under ultra-sound guidance riduces NSAID consumption in symptomatic hip osteoarthritis patients in a long follow-up. Data from Italian registry.

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) consumption is strictly related to a high gastrointestinal and cardiovascular mortality and morbidity rate. Osteoarthritis Research Society International (OARSI) recommendations in patients with symptomatic hip or knee OA stated that NSAIDs should be used at the lowest effective dose but their long-term use should be avoided if possible. OARSI guidelines for the treatment of the hip OA include the use of viscosupplementation, which aims to restore physiological and rheological features of the synovial fluid. OBJECTIVE: Aim of this multicentric, open and retrospective study is to investigate if NSAID consumption may be reduced by the use of ultrasound-guided intra-articular injection of several hyaluronic acid (HA) products in hip joint administered in patients affected by symptomatic hip OA. MATERIALS AND METHODS: Patients affected by mono or bilateral symptomatic hip OA according to American Rheumatology Association (ARA) criteria, radiological OA graded II-IV (Kellgren and Lawrence) entered the study and were administered with ultrasound-guided intra-articular injection of hyaluronic acid products. As a primary endpoint, consumption of NSAIDs was evaluated by recording the number of days a month (range 0-30) the patient had used NSAID during the previous month, reported at each visit during the 24 months follow-up period. Secondary endpoints included further analysis for subgroups of patients categorized for Lequesne index score, Kellgren-Lawrence score, pain visual analogue scale (VAS) score, ultrasound pattern, age, hyaluronic acid used. RESULTS: 2343 patients entered the study. Regarding primary endpoint, the consumption of NSAIDs was reduced of 48.2% at the third month when compared with baseline values. This sparing effect increased at 12th and 24th month with a reduction respectively of 50% and 61% in comparison to baseline values. These differences were statistically significant. CONCLUSIONS: These data point out that intraarticular hyaluronan preparations provide OA pain relief and reduce NSAIDs consumption in a large cohort of patients for a long period of follow-up. Multiple courses of viscosupplementation (vs) are required to maintain low dose of NSAID consumption over time. NSAIDs consumption is strictly related to an high gastrointestinal and cardiovascular mortality and morbidity rate, instead HA intra-articular treatment is well tolerated and is associated with a low incidence of adverse effects. For these reasons further studies evaluating cost-effectiveness and cost-utility of VS in the management of hip OA are required.

Interstitial lung disease in rheumatoid arthritis in the era of biologics.

Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.

Can Cyclosporine-A associated to methotrexate maintain remission induced by anti-TNF agents in rheumatoid arthritis patients? (Cynar pilot study).

Biological therapies, such as etanercept, adalimumab and infliximab, have demonstrated good efficacy in inducing rheumatoid arthritis to low disease activity levels. Nevertheless, their cost, as well as the related risk of side effects, especially in long-term therapies, are still high. Furthermore, there is a good deal of evidence proving loss of efficacy of such therapies in the long term, often necessitating the shift from one specific anti-TNF biological treatment to another. There are also other open debates on the amount of time a patient should undergo an anti-TNF therapy, on the possibility of inducing a complete remission in early arthritis and, once remission or low disease activity is obtained, on the possibility of interrupting the anti-TNF-based therapy. In this study we investigated whether A-Cyclosporin and Methotrexate association may be effective in maintaining low disease activity obtained by anti-TNF therapies. Twenty-three rheumatoid arthritis-affected patients, whose diagnosis was made according to ACR criteria, with a disease duration of less than 3 years, and DAS28<3.2 that reached a level of low disease activity within 6-8 months from beginning anti-TNF and Methotrexate therapy, were enrolled in the study. After the suspension of anti-TNF therapy, patients were started on A-Cyclosporine (2-3 mg/kg/day) and Methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation Rate (ESR), and C Reactive Protein (CRP) were all tested at time 0 and at 6 months, as well as liver and kidney profiles, after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and Methotrexate therapy. Side effects were also recorded. Of 23 patients undergoing the A-Cyclosporin and Methotrexate therapy for maintaining low disease activity in rheumatoid arthritis obtained by 6-8 months of anti-TNF therapy, 21 completed the study with a 6 month follow-up. Thirteen patients maintained clinical parameters within low disease activity values, while 8 patients showed an increase in DAS28 and other parameters. Only two patients showed an increase in blood pressure that was diagnosed after two months from the beginning of the A-Cyclosporin and Methotrexate therapy. The reduction in the dosage of A-Cyclosporin from 3mg/kg/day to 2mg/kg/day caused a slow normalization of blood pressure values. Our data seem to suggest that more than half of the patients undergoing A-Cyclosporin and Methotrexate therapy seemed to maintain low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.

A new technical contribution for ultrasound-guided injections of sacro-iliac joints.

INTRODUCTION: Sacroiliac joint (SIJ) represents a difficult location for local therapies, as intra-articular injections may be hard to execute, especially in particular conditions such as chronic inflammatory diseases. However, in selected patients, local therapies may be considered. Some recent studies demonstrated the feasibility of ultrasound (US)-guided injection of SIJ, but still a complete explanation and definition of the technique is needed. MATERIALS AND METHODS: Seven patients, four males and 3 females, affected by mono or bilateral sacroiliitis entered the study. Each patient received 40 mg of acetonide triamcinolone for each SIJ, intra articular (IA) US-guided injection. The technical originality proposed in this study consists in the spinal needle insertion in the middle of the cranial long side of the linear transducer with an orientation of about 10 degrees, determining shorter needle insertion for reaching joint space and consequently probably granting lesser pain and traumatism for patients. RESULTS: A total of 22 injections was performed. The longer follow-up time obtained was 18 months in 3 patients. All patients reached at least a 6 month follow-up. All patients reported an amelioration in pain that lasted for at least 6 months. No systemic adverse events were reported or observed. Complete visualization of SIJ and of needle placement was performed by US imaging, while compound proper injection was also visualized by Color-Doppler US imaging. DISCUSSION: Actually, sacroiliac joint intraarticular injections are often performed under fluoroscopy or Computerized Tomography guidance. Such techniques present several limitations, especially for repeated injections, such as the use of ionizing radiations, the need of a contrast agent and the direct and indirect costs connected. US guidance in IA SIJ injections may represent an easily repeatable imaging technique for needle placement and a precious tool for detecting inflammatory activity of the joint.