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.

Restoration of peripheral blood natural killer and B cell levels in patients affected by rheumatoid and psoriatic arthritis during etanercept treatment.

Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-α agent used in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on the effects of anti-TNF-α on peripheral blood cells. We aimed to evaluate peripheral blood cells in RA and PsA patients during ETN treatment and to explore their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients who started ETN were included into the study and evaluated prospectively before the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were studied in terms of disease activity score on 28 joints (DAS28), clinical response and laboratory findings. Natural killer (NK) cells, B cells and T cells were characterized by immunophenotyping. Both the RA and the PsA patients showed reduced NK and B cell count before ETN treatment compared with controls. A negative correlation was demonstrated between DAS28 and B cell count in RA patients at baseline. Sustained significant increase of NK and B cells up to normal levels was observed in RA and PsA patients along ETN treatment. Increase of NK cell count was associated with a good-moderate clinical response to ETN in both RA and PsA patients. During ETN treatment peripheral blood NK and B cells levels were restored in RA and PsA patients. Correlations between NK and B cells with disease activity were observed, suggesting that those effects could be mediated by ETN treatment.

Evidence of impaired sense of smell in hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is an autosomal-dominant disorder resulting from C1-inhibitor (C1INH) deficiency. Smell impairments were found in patients affected with systemic lupus erythematosus, that, similarly to HAE, is characterized by the activation of the classical complement pathway with C4 consumption. In this study, we aimed at evaluating the sense of smell in patients with HAE. METHODS: Thirty patients with HAE and 30 healthy age- and sex-matched controls were evaluated for olfactory functions using the 3-stages Sniffin'-Sticks kit (threshold, discrimination, and identification [TDI]). TDI scores were analyzed according to complement levels (C1INH, C3, C4 and CH50), Beck depression inventory (BDI-II) and danazol treatment. RESULTS: A significant decrease in olfactory function was observed in patients affected with HAE compared with controls in total TDI score (P < 0.001), and in the discrimination (P < 0.001) and identification scores (P = 0.012). Anosmia was present only in patients with HAE (3.3%) who also exhibited more frequently hyposmia (53.3%vs 3.3%, P < 0.0001). Complement levels were reduced in patients with HAE. C4 serum levels showed positive correlation with total TDI score (P < 0.001), and with discrimination (P = 0.002) and identification (P = 0.011) scores. CH50 complement levels showed positive correlation with total TDI score (P < 0.001), and with threshold (P = 0.002) and discrimination (P = 0.011) scores. Sex, age, danazol treatment, BDI-II scores were not different between the patients and controls and did not influence TDI scores significantly. CONCLUSION: Evidence for an impaired sense of smell was found in patients with HAE. The reduction in olfactory function in these cases seems to correlate with complement C4 and CH50 levels. Immune and genetic mechanisms might play a role in this defect.

Differences in biologics for treating ankylosing spondylitis: the contribution of network meta-analysis.

OBJECTIVE: Ankylosing Spondylitis (AS) is a chronic form of arthritis of unknown origin affecting the spine. In this study, we aimed to identify clinical and safety profiles of adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, and secukinumab that are biologic agents (biologics) mainly used for the treatment of AS, and to understand differences between them. MATERIALS AND METHODS: An extensive literature research was performed in MEDLINE and EMBASE in order to identify all network meta-analysis (NMA) and/or mixed treatment comparison (MTC) papers. NMA and/or MTC, with a ranking of the effectiveness of biologics in AS, were included in the analysis, and the adhesion to ISPOR guidelines was investigated. RESULTS: 60 studies were identified; after applying exclusion criteria methods, 7 studies underwent further analysis. Infliximab was the drug that exhibited the highest probability for achieving clinical efficacy by ASAS20 at 12 and 24 weeks. Considering only subcutaneous biologics, Golimumab achieved the highest probability for achieving the ASAS20 response at 12 weeks. CONCLUSIONS: Results from NMA on the use of biologics in AS indicates infliximab emerged as the drug with the highest probability of obtaining ASAS20 response both at 12 and 24 weeks of treatment.

Biologics for psoriatic arthritis: network meta-analysis in review.

OBJECTIVE: A review of network meta-analysis to assess efficacy and safety of biologics for the treatment of psoriatic arthritis (PsA). MATERIALS AND METHODS: A systematic search was conducted on electronic databases to identify Bayesian meta-analysis reporting clinical parameters of efficacy, safety and cost-effectiveness of biologics that are approved for the treatment of PsA patients. RESULTS: We identified 19 studies and included them for review. There is insufficient statistical evidence to demonstrate clear differences in effectiveness between available biologic agents for PsA due to many differences in methods and clinical parameters reported in the studies. Old biologics are reported to be safe. CONCLUSIONS: New molecules approved for the treatment of PsA appear promising treatments but further comparative studies methodologically well-conducted are necessary. It is also necessary to follow strictly international recommendations to conduct NMA to better help physicians and decision-makers in making appropriate decisions.

A review of network meta-analysis comparing biologics in the treatment of rheumatoid arthritis.

OBJECTIVE: Even though in recent years significant improvements have been made in the management of patients with rheumatoid arthritis due to the introduction of biologic agents, it is still difficult to identify the most effective and safest available treatment. The choice and comparison between biological agents are a challenge, for only limited head-to-head clinical studies are available. The aim of this manuscript is to review the published network meta-analysis (NMA) to gain a better understanding of efficacy and safety of biological agents and small molecules in the management of RA patients. MATERIALS AND METHODS: We used MEDLINE and EMBASE to identify network meta-analyses from 2008 to June 2019 comparing efficacy and safety of licensed biological agents and tsDMARDS at the approved dosages using predefined text words related to the topic. The following scenarios have been investigated: patients not responding to csDMARD (cDMARDs - IR); csDMARD naïve patients; patients not responding to biologics (bDMARDs - IR); patients in biological monotherapy. RESULTS: On the basis of the data present in the literature, we are able to hypothesize some trends of response in terms of efficacy in different subsets of patients, for example patients in monotherapy, bDMARds unresponsive patients, and Methotrexate-naive patients. The differences of the results presented in many works are due to the different inclusion criteria used in the studies, the type of biologics agent used in each study (according to the available molecules in the different years of publication), as well as differences in the methodology of NMA and in the presentation of the data. CONCLUSIONS: We suggest that the next NMA follows the indications suggested by the Professional Society for Health Economics and Outcomes Research (ISPOR) so that the results are comparable and comprehensible.

It Is the Time to Think About a Treat-to-Target Strategy for Knee Osteoarthritis.

Osteoarthritis (OA) is a rheumatic disease that affects the well-being of the patient, compromises physical and mental function, and affects other quality of life aspects. In the literature, several evidence-based guidelines and recommendations for the management of knee osteoarthritis (KOA) are available. These recommendations list the different therapeutic options rather than addressing a hierarchy between the treatments and defining the real target. Therefore, a question arises: are patients and physicians satisfied with the current management of KOA? Actually, the answer may be negative, thus suggesting a change in our therapeutic strategies. In this article, we address this challenge by suggesting that it is time to develop a "treat to target strategy" for KOA.

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.