Alberto Migliore

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. 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. 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. 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. 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.

We have developed a standardized technique for 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. The purpose of this study was to examine the safety of this technique in an extended series of patients.

Objective: To evaluate the efficacy and the tolerability of viscosupplementation (VS) with hyaluronic acid (Hylan GF 20) in a cohort of 36 patients affected by hip osteoarthritis through a 18 months follow-up. Methods: Viscosupplementation was performed with an anteriorsagittal approach, under ultrasound guidance. 36 patients were administered hyaluronic acid intraarticularly in the hip, with a unique injection of Hylan G-F20, which could be repeated after at least 3 months. Treatment efficacy was assessed by functional index WOMAC, pain evaluation on a visual analogue scale and NSAID consumption. All such parameters were recorded at the time of the first injection and then 3, 6, 9, 12 and 18 months later. Results: Statistically significant reduction of all parameters was observed three months after the injection, and was still maintained at the timepoints 6, 9, 12 and 18 months. No local side effects have been observed, nor systemic complications. Conclusions: Our data show that viscosupplementation is a promising approach for hip osteoarthritis, providing beneficial effects in a long-tern follow up. Yet, the topic deserves further and wider studies, so to define the number of injections to administer and suggest a fit interval between subsequent injections.

Increasing amounts of data have recenlty been published regarding ultrasonographic (US) findings of osteoarthritic joints, but very few data concern hip joints. In the current study we described US patterns concerning 490 patients affected by symptomatic hip osteoarthritis (OA) who underwent to intra-articular injections of hyaluronic products under US guidance. All patients were studied by US and X-ray of hip, clinical evaluation was assessed by the followings indexes: Lequesne, pain VAS, ICED, Global Physician Assessment and Global Patient Assessment. US findings were summarized in four main patterns, effusion and synovial proliferation were also detected. The aim of this study was to correlate US findings with clinical assessment and radiographic findings (according to Kellegren- Lawrence classification). Pearson’s r correlation coefficient were computed and come out significant and positive between X ray and US patterns and between clinical indexes and US patterns. Also the correlation between K-L score and US patterns showed a significant positive correlation indicating that higher K-L scores are associated with increasing abnormal US findings. Our data suggest that ultrasonography of the hip may give useful information about the state of synovial membrane, synovial fluid, joint margins and bone profile in hip OA. Further studies are needed to evaluate their prevalence in hip OA symptomatic and not-symptomatic patients and their correlation to treatment outcome.

Hip is a site very commonly affected by osteoarthritis (OA), yet few data exist in literature regarding intra-articulaar use of hyaluronic acid in this pathology. We evaluated the efficacy of Hylan G-F 20 hip viscosupplementation performed under ultrasound guidance. We enrolled 26 patients affected by symptomatic hip OA and treated them with a single intraarticular injection of Hylan G-F 20, which could be repeated every two months. The injection was performed under ultrasound guidance with an antero-superior approach. Treatment efficacy was assessed through Lequesne index, visual analogue scale (VAS) pain quantification, and NSAID intake at the timepoint zero (baseline), and after 2, 6 and 12 months. We observed a statistically significant reduction of all considered parameters at the timepoints 2 and 6 months, when compared to baseline. At 12 months the changes were still statistically significant for all parameters for about 50% of the patients. No side effect was observed, nor systemic complication. Viscosupplementation is a promising approach for hip OA, although further and wider studies are wanted to determine how long the beneficial effect lasts, and what is the optimal number of injections to administer.

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. 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. 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. 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. 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.

Young adult hip osteoarthritis (OA) is a noteworthy problem, although rarer than the elderly form of the disease, causing limitations in social and working activities and prospects. Treatment options are scarce and surgical procedures, frequently necessary, imply the major drawback of revising the prostheses periodically, whereas chronic nonsteroidal anti-inflammatory drugs (NSAID) consumption may provoke side effects. To explore alternative options to both surgery and long-term NSAID use, especially in the case of young patients, viscosupplementation seems to appear as an appropriate tool to relieve pain, ameliorate the function and delay surgery. In this study we tackle the issue of the use of hyaluronic acid (HA) injections in young adults with symptomatic hip OA. These data, collected from 78 young patients, show that viscosupplementation is a safe procedure, and may provide significant relief from pain and functional recovery. Larger controlled studies are needed to establish otpimal treatment strategies and clinical factors predictive of treatment response.

Background: A number of anaemic cancer patients are not responsive to treatment with recombinant human erythropoietin (rHuEPO). The aim of the present study is to investigate whether serum levels of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and additional laboratory parameters, together with clinical variables, can predict the clinical outcome of treatment with rHuEPO in anaemic cancer patients. Patients and methods: Thirty-five cancer patients and 25 healthy controls were enrolled in this study. Patients were treated with epoetin alfa at the dose of 150 IU/kg s.c. three times a week for 12 weeks. If the haemoglobin (Hb) level failed to improve at least 2 g/dl above baseline by week 6 of treatment, dose was increased to 300 IU/kg s.c. for the remainder of the treatment period. All patients filled out the Brief Fatigue Inventory (BFI), a questionnaire for the self-evaluation of cancer-related fatigue. Serum samples from patients and control groups were frozen at −80°C and TNF-α, IL-1β and IL-6 were later examined by enzyme-linked immunosorbent assay. Results: Fatigued cancer patients had significant higher levels of circulating TNF-α, IL-1β and IL-6 than healthy controls. Responders (Rs) to erythropoietin had significant lower medium levels of TNF-α and IL-6 than nonresponders (NRs). Fatigued patients with a general BFI score ≥6 presented higher medium level of cytokines than nonfatigued patients (general BFI score Conclusions: High serum levels of TNF-α and IL-6 at the baseline are significantly correlated with a negative response to administration with rHuEPO. Thus, pretreatment evaluation of TNF-α and IL-6 serum levels can help to select those patients who are most likely to benefit from treatment with rHuEPO. On the contrary, Hb level, red blood cell count, lactate dehydrogenase and BFI score do not predict the outcome of treatment with rHuEPO.