Unmet needs on the current medical management of Cushing's syndrome: results from a Delphi panel of Italian endocrinologists.

BACKGROUND: Cushing's syndrome (CS) is a rare clinical condition caused by excessive cortisol secretion from adrenal glands. CS is associated with increased mortality and morbidity; therefore, a prompt diagnosis and an effective therapeutic approach are strongly necessary to improve the patient's clinical management. The first-line treatment for CS is surgery, while medical treatment has historically played a minor role. However, thanks to the availability of novel compounds, the possibility of improving hypercortisolism control using different drug combinations emerged. PURPOSE: No absolute recommendations are available to guide the therapeutic choice for patients with CS and, consequently, the awareness of unmet needs in CS management is growing. Although new data from clinical trials are needed to better define the most appropriate management of CS, an expert consensus approach can help define unmet needs and optimize the current CS management and treatment. METHODS: Twenty-seven endocrinologists from 12 Italian regions, working among the main Italian referral centers for hospital endocrinology where they take care of CS patients, were involved in a consensus process and used the Delphi method to reach an agreement on 24 statements about managing CS patients. RESULTS: In total, 18 statements reached a consensus. Some relevant unmet needs in the management of CS were reported, mainly related to the lack of a pharmacological treatment successful for the majority of patients. CONCLUSION: While acknowledging the difficulty in achieving complete disease control, a significant change in CS management requires the availability of medical treatment with improved efficacy and safety over available therapeutic options at the time of the current study.

Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies.

OBJECTIVE: To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. METHODS: We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. RESULTS: The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). CONCLUSIONS: Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.

Impact of Covid-19 pandemic on injection-based practice: report from an Italian multicenter and multidisciplinary survey.

Background: There are no papers exploring the impact of COVID-19 pandemic on the injection-based practice in patients affected by different rheumatic diseases, including osteoarthritis. The aim was to investigate the impact of COVID-19 pandemic on injection-based practice trough the Italian country. Study design: A survey-based retrospective cross-sectional study. Methods: An Italian-language questionnaire was developed by a group of senior researchers and distributed by e-mail to some Rheumatology, Orthopedic and Rehabilitation Units from different geographic areas of Italy. The survey included information about the number of injections performed during COVID-19 pandemic (stratified by injected agents and injected joint), in comparison to the pre-pandemic period, and the possible reasons behind an eventual reduction. Responses were collected and descriptive analysis calculated. Results: Eleven centers of the National Health Service completed the survey. The activities of the injections services significantly decreased across the country with a percentage of reduction of 60% compared to the pre-pandemic period. A significant reduction of both intra-articular and peri-articular injections was registered. Among intra-articular. treatments, the most affected ones were the hyaluronic acid injections, when compared to corticosteroids. A significant decrease of the total amount of peri-articular injections was observed. The strict government restrictions and the fear of patients to become infected represented the most limiting factors. Conclusions: The reported decrease of the injection-based practice in our country during the COVID-19 pandemic highlights the detrimental effects of the COVID-19 pandemic on the management of chronic musculoskeletal diseases with possible negative consequences in terms of disability and quality of life.

One-year follow-up showing effects of single intra-articular injection of hyaluronic acid (1,500-2,000 kDa) in symptomatic knee osteoarthritis.

Clinical evidence on knee osteoarthritis suggests that intra-articular administration of hyaluronic acid may be useful in the management of patients with persistent pain. This study assesses the duration of effectiveness of a single intra-articular hyaluronic acid injection in a large population of patients with knee osteoarthritis. This retrospective post-marketing cohort study collected data from the ANTIAGE Registry (http://www.antiagefbf.it/registro), selecting patients of age ≥ 40 years, with symptomatic knee osteoarthritis (Kellgren-Lawrence grade I-III) of ≥ 12 months duration, and ≥12 months of follow-up. Patients had received a single intra-articular injection of high molecular weight hyaluronic acid (1,500-2,000 kDa) at baseline. WOMAC Osteoarthritis Index total scores measured using the LK 3.1 scale and 10 cm VAS pain scores were evaluated before IA Injection and at 6, 9, 10, 11 and 12 months. Blood cell counts, uricemia, erythrocyte sedimentation rates and levels of C-reactive protein were measured at baseline and 12 months. Time from initial treatment to second injection up to 12 months was recorded to assess event-free survival. Included patients (n=187) were 53.5% female and had a mean (±SD) age at baseline of 62 (±16.6) years and mean (±SD) body mass index of 26.2 (±2.5) kg/m2. Mean (±SD) WOMAC index total score and VAS pain scores were 60.9 (±7.1) and 5.9 cm (±1.8), respectively. There were statistically significant reductions compared to baseline in mean WOMAC index total score and VAS pain score at all time points (p less than0.01 at 6 and 9 months; p less than 0.05 at 10, 11 and 12 months for both parameters). These results support the clinical effectiveness and safety of hyaluronic acid for up to 12 months for pain relief and function improvement in patients with knee osteoarthritis, confirming previous data on intra-articular administration of hyaluronic acid as chronic therapy in the management of knee osteoarthritis.

The impact on disability of initial treatment with methotrexate in patients with rheumatoid arthritis: results from the MARI study.

The study aimed to assess in a population of subjects with rheumatoid arthritis (RA) treated with methotrexate (MTX) how the initial approach to the treatment influenced subsequent disability. We performed a cross-sectional analysis of data collected during the baseline visit of the MARI study, a multicenter observational study on patients with RA on treatment with MTX for at least 12 months. Subjects who fulfilled the Health Assessment Questionnaire (HAQ) were included in the evaluation. For every patient we retrospectively evaluated the disease duration, the duration of symptoms before the diagnosis, the time elapsed before first MTX treatment, the initial MTX dose, and the concomitant medications in the first six months of therapy. Disability was defined as a DI-HAQ score ≥1. The study population included 1015 subjects. Patients with a DI-HAQ score ≥1 had a longer duration of symptoms before diagnosis, a higher delay in treatment initiation, a lower initial dose of MTX and a more frequent co-treatment with symptomatic drugs. Disability was found less frequently in subjects treated with other concomitant disease modifying anti-rheumatic drugs (DMARDs) but not with biological agents. Logistic regression analysis identified as significant predictors of disability: older age, female sex, a longer time to complete diagnosis, a delay in starting MTX treatment higher than 6 months, and a concomitant treatment with symptomatic drugs, while a combination therapy with other DMARDs was associated with a lower risk of disability. A late diagnosis and a delay in starting a treatment with MTX are associated with poorer functional outcomes in patients with RA.

Suboptimal methotrexate use in rheumatoid arthritis patients in Italy: the MARI study.

OBJECTIVES: Methotrexate (MTX) is the first choice in the treatment of rheumatoid arthritis (RA), but the doses and regimens vary significantly. For this purpose, we conducted an observational study on the use of MTX for RA in Italy (MARI study). METHODS: The MARI study included 1,327 RA patients on MTX treatment for at least 12 months, at 60 Italian rheumatology units. Concomitant medications with corticosteroids, other DMARDs or biological therapies were recorded. The clinical assessment included the Disease Activity Score 28 (DAS28) and the serological positivity for the rheumatoid factor or for the anti-citrullinated protein antibodies. RESULTS: The included patients were treated with either oral (n=288) or parenteral (n=1039) MTX. Only 15.5% of the total number of the patients was on adequate MTX dose (i.e. ≥ 15 mg for the oral route of administration and >12 mg for the parenteral one). The initially established MTX dose was modified in 37.1% of the patients, for intolerance or clinical criteria. A DAS28 remission (DAS28 <2.6) was observed only in 58.5% of the cases, while 52.9% of the patients still presenting an active form of the disease were on suboptimal doses of MTX. CONCLUSIONS: The weekly dose of MTX prescribed for the treatment of RA is often suboptimal, even in conditions of inadequate control of the disease activity. The recommendations for the use of MTX in RA patients should take into account the efficacy and tolerability data derived from its use in real clinical practice.

MANAGEMENT OF PSORIATIC ARTHRITIS: SHOULD THE INTERACTION BETWEEN DERMATOLOGISTS AND RHEUMATOLOGISTS IN CLINICAL PRACTICE BE INTENSIFIED?

Psoriatic arthritis is an inflammatory seronegative spondyloarthropathy that occurs in approximately 25% of patients with psoriasis and is a progressive and severely disabling disease. Most patients have had psoriasis for several years before the development of arthritis or develop the joint and skin condition simultaneously. Given the absence of specific diagnostic test for psoriatic arthritis, clinical findings remain the standard criteria for the diagnosis. Patients with psoriasis presenting to the dermatologist for management of their skin disease may have joint symptoms related or not to psoriatic arthritis and similarly arthritic patients presenting to a rheumatologist for the management of psoriatic arthritis may have skin lesions related or not to psoriasis. In this paper an expert panel of specialist belonging to the “Associazione Dermatologi Ospedalieri Italiani” (ADOI) and “Collegio dei Reumatologi Ospedalieri Italiani” (CROI) analysed the international literature and scientific recommendations and also investigated the Italian setting. It has been demonstrated in the literature that a multidisciplinary clinical setting may benefit patients with psoriatic arthritis from both diagnostic and therapeutic points of view. The comparative analysis of the Italian clinical records used by ADOI and CROI have highlighted some substantial differences. Collaboration between the dermatologist and rheumatologist allows for a more complete appreciation of the overall skin and musculoskeletal disease burden, and subsequently leads to a more comprehensive treatment approach.

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.

Increased risk of osteoporosis in postmenopausal women with type 2 diabetes mellitus: a three-year longitudinal study with phalangeal QUS measurements.

Type 2 diabetes mellitus (T2DM) is associated with a higher risk of fractures even in presence of normal or increased bone mineral density. The purpose of this three-year longitudinal study was to evaluate the risk of osteoporotic fractures by assessing the changes of Quantitative Ultrasound (QUS) parameters in a group of postmenopausal women with type 2 diabetes mellitus (T2DM) compared with non-diabetic controls. The measurements were taken on a group of 18 postmenopausal women affected by T2DM and 18 healthy age-matched controls, aged 55-70 years, referring to the Osteolab laboratory at the ISBEM Research Institute (Brindisi, Italy) between 2009 and 2013. Subjects had baseline and 3-year follow-up measurements with phalangeal QUS carried out by a DBM Sonic Bone Profiler 1200 (Igea®); medical history, current drug therapies and risk factors for fractures were recorded for each patient. The analyzed phalangeal QUS parameters were Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), Fast Wave Amplitude (FWA) and Signal Dynamic (SDy). At the baseline visit we found no statistically significant difference between T2DM and non-diabetic patients when looking at phalangeal QUS parameters. At the three-year follow-up visit, a significantly higher decrease of both BTT (P<0.001) and AD-SoS (P<0.001) parameters was found in the T2DM group. On the contrary, the decrease of FWA was significantly higher in non-diabetic controls (P<0.001). Our data confirm the ability of phalangeal QUS to detect differences in the risk of osteoporotic fractures in T2DM postmenopausal women compared to non-diabetic controls. The study suggests that T2DM women present a higher cortical porosity and increased trabecular bone density compared to non-diabetic controls, respectively shown by the higher decrease of both AD-SoS and BTT and the lower decrease of FWA.

Psoriatic arthropathy in patients with previous neoplasia: a case series of four patients treated with secukinumab and literature review.

OBJECTIVE: Psoriasis and psoriatic arthritis (PsA) are closely linked to cancer, as supported by the literature. Systemic treatments for psoriasis and PsA, namely non-biological disease-modifying anti-rheumatic drugs (DMARDs), have been associated with increased cancer risk in both conditions. New, more effective biological DMARDs (bDMARDs) do not seem to be associated with higher overall cancer risk compared to those not receiving bDMARDs, opening up possibilities for treating patients with previous or ongoing oncological disease alongside psoriasis and PsA. However, limited literature exists on treating PsA patients with cancer with bDMARDs. This study aims to assess the safety of secukinumab, a bDMARD, in patients with PsA and concurrent cancer. Here, we describe a case series of four patients with PsA treated with bDMARD secukinumab and review the literature on the subject. CASE SERIES: We assessed the laboratory parameters and clinical characteristics of 4 patients with PsA treated with the bDMARD secukinumab and followed up until 30 months. Three patients had oncological disease in remission, while one had active neoplasia. No cancer progression was observed during the treatment of these patients with secukinumab. CONCLUSIONS: In conclusion, our case series, consisting of four PsA patients with concurrent neoplasia treated with secukinumab, showed no evidence of cancer progression and represents the first case of PsA described in the literature treated during active oncological disease, lending support to the safety of secukinumab for the treatment of patients with PsA and concomitant neoplasia.

Long-term safety of anti-TNF adalimumab in HBc antibody-positive psoriatic arthritis patients: a retrospective case series of 8 patients.

Immunosuppressive drugs commonly used in the treatment of psoriatic arthritis make patients more susceptible to viral, bacterial, and fungal infections because of their mechanism of action. They not only increase the risk of new infections but also act altering the natural course of preexisting infections. While numerous data regarding the reactivation of tuberculosis infection are available in the literature, poor information about the risk of reactivation or exacerbation of hepatitis viruses B and C infections during treatment with biologics has been reported. Furthermore, reported series with biological therapy included short periods of followup, and therefore, they are not adequate to verify the risk of reactivation in the long-term treatment. Our study evaluated patients with a history of hepatitis B and psoriatic arthritis treated with adalimumab and monitored up to six years. During the observation period, treatment was effective and well tolerated in all patients, and liver function tests and viral load levels remained unchanged.

Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

Ranking antireabsorptive agents to prevent vertebral fractures in postmenopausal osteoporosis by mixed treatment comparison meta-analysis.

INTRODUCTION: Bisphosphonates are considered as a first-line therapy for the prevention and treatment of osteoporosis, showing in double-blind, randomized, controlled trials a significant reduction of incidence of new vertebral fractures compared to placebo. Recently also, Denosumab has been shown to reduce the appearance of new vertebral fractures by blocking RANK. There are not head to head comparative studies between the above mentioned drugs. Mixed treatment comparison, an extension of traditional meta-analysis, is able to compare simultaneously several drugs across a range producing a synthetic evidence of efficacy and a range of probability as to the best treatment. OBJECTIVES: The aim of this study is to simultaneously compare alendronate, risedronate, ibandronate, zolendronate and denosumab in the prevention of OP vertebral fractures in a Bayesian meta-analysis for assessing indirect comparisons. MATERIALS AND METHODS: A search for randomized controlled trials involving alendronate, risedronate, ibandronate, zolendronate and denosumab was conducted using several databases. Randomized controlled trials (RCTs) with a double blind treatment period of at least 3 years were included. Men and Glucorticoid Induced osteoporosis, RCTs having as primary or secondary endpoints continuous values as body mineral density (BMD) and studies comparing different dosing regimens of the same agent, which are not used in clinical practice, were excluded. Only fully published reports were considered. RESULTS: A total of 9 RCTs were identified providing data on 31,393 participants. Zolendronate had the highest probability (52%) of being the most effective treatment towards placebo, followed by denosumab (46% probability), ibandronate and then alendronate and risedronate against placebo. CONCLUSIONS: Although the mixed treatment comparisons among alendronate, risedronate, ibandronate, zolendronate and denosumab did not show a statistically significant difference, this analysis suggests that zolendronate, compared to placebo, is expected to provide the highest rate of reduction in vertebral fractures affecting osteoporosis affected patients.

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.

Italian Society for Rheumatology recommendations for the management of hand osteoarthritis.

Hand osteoarthritis (OA) is a common and potentially disabling disease, with different features from hip and knee OA so that a specific therapeutic approach is required. Evidence based recommendations for the management of hand OA were developed by the European League Against Rheumatism (EULAR) in 2006. The Italian Society for Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the EULAR recommendations for the management of hand OA. The multidisciplinary group of experts included specialists involved in the management of patients with hand OA. In order to maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were reformulated in terms of a search query and for every recommendation a systematic search was conducted updating EULAR recommendations' review. The propositions were translated in Italian and reformulated basing on collected evidences and expert opinion. The strength of recommendation was measured for each proposition with the EULAR ordinal and visual analogue scales. The original 11 propositions of EULAR recommendations were translated and adapted to Italian context. Further evidences were collected about non-pharmacological therapies, local treatments, intra-articular injection with SYSADOA and corticosteroids, and surgery. The SIR has developed updated recommendations for the management of hand OA adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with hand OA.

Can the association of Ciclosporine A and Methotrexate maintain remission/low disease activity induced by etanercept in early Rheumatoid Arthritis patients? Evaluation by Magnetic Resonance Imaging.

The opportunity to induce remission/low disease activity in Rheumatoid Arthritis (RA) patients has been achieved in recent years by the adoption of more sensitive diagnostic methods [Magnetic Resonance Imaging (MRI), ultrasonography] and early aggressive treatments (combination of biologics and synthetic DMARDs). On the other hand, data are still scarce and contrasting about the management of long-term remission. The aim of this preliminary study is to evaluate whether the association of Methotrexate + Ciclosporine A (MTX + CSA) therapy in early RA (eRA) patients is able to maintain remission/low disease activity and avoid structural progression, evaluated by MRI. Etanercept was suspended in patients who reached remission/low disease activity and CSA+MTX therapy was introduced (T0), all patients continued to receive MTX; at this time MRI showed mild/moderate synovitis and erosions in all the patients; 1-year after (T1), a slight reduction in mean synovitis, bone edema and total score was observed, whereas the erosion score was unchanged. The mean DAS44 remained stable from T0 to T1 and 6/7 patients maintained a low disease activity score. No side effects were reported. These results confirm the good clinical efficacy and safety of the combination therapy CSA+MTX in eRA patients and demonstrate a parallel arrest of structural damage evaluated by MRI 1-year after etanercept suspension.

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.

Intradermal therapy (mesotherapy): the lower the better.

BACKGROUND: Intradermal therapy (mesotherapy) is a technique used to inject drugs into the surface layer of the skin. The intradermal micro deposit allows to modulate the kinetics of drugs, slowing down its absorption and prolonging the local mechanism of action. This technique is applied in the treatment of some forms of localized pain when a systemic drug-saving effect is useful, when it is necessary to synergize with other pharmacological or non-pharmacological thera-pies, when other therapies have failed or cannot be used. AIM: The purpose of our study was to evaluate the effect of a mixture with respect to its lower concentration. We also wanted to evaluate the number of sessions needed to reach the therapeutic goal (50% reduction in pain from baseline) in patients with acute or chronic neck pain. METHOD: We analyzed retrospectively data from 62 patients with cervicobrachial pain treated with intradermal drugs. Group A received a mixture of drugs; group B received half the dose of drugs. RESULTS: Patients who received a lower concentration of drugs achieved similar results to those who received a higher dose. The therapeutic goal was achieved on average with 3.5 + 1.7 sessions on a weekly basis (min 1; max 9). Subjects in group A required 4+1.7 treatments (min 1; max 9), while subjects in group B required 3+1.5 treatments (min 1; max 7). CONCLUSIONS: Our study confirms that even a lower dose of drugs can induce a clinically useful result. This study confirms that the useful effect of mesotherapy is only partly due to the pharmacological action. Further randomized prospective studies are needed to standardize the technique in the various pain syndromes, but it is recommended to follow the guidelines of the Italian Society of Mesotherapy to ensure patients receive appropriate treatment.

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.