Socio-economic inequalities in the use of drugs for the treatment of chronic diseases in Italy.

BACKGROUND: Since the use of medicines is strongly correlated to population health needs, higher drug consumption is expected in socio-economical deprived areas. However, no systematic study investigated the relationship between medications use in the treatment of chronic diseases and the socioeconomic position of patients. The purpose of the study is to provide a description, both at national level and with geographical detail, of the use of medicines, in terms of consumption, adherence and persistence, for the treatment of major chronic diseases in groups of population with different level of socioeconomic position.  METHODS: A cross-sectional study design was used to define the "prevalent" users during 2018. A longitudinal cohort study design was performed for each chronic disease in new drug users, in 2018 and the following year. A retrospective population-based study, considering all adult Italian residents (i.e. around 50.7 million people aged ≥ 18 years). Different medications were used as a proxy for underlying chronic diseases: hypertension, dyslipidemia, osteoporosis, diabetes and chronic obstructive pulmonary disease. Only "chronic" patients who had at least 2 prescriptions within the same subgroup of drugs or specific medications during the year were selected for the analysis. A multidimensional measures of socio-economic position, declined in a national deprivation index at the municipality level, was used to identify and estimate the relationship with drug use indicators. The medicine consumption rate for each pharmacological category was estimated for prevalent users while adherence and persistence to pharmacologic therapy at 12 months were evaluated for new users. RESULTS: The results highlighted how the socioeconomic deprivation is strongly correlated with the use of medicines: after adjustment by deprivation index, the drug consumption rates decreased, mainly in the most disadvantaged areas, where consumption levels are on average higher than in other areas. On the other hand, the adherence and persistence indicators did not show the same trend. CONCLUSIONS: This study showed that drug consumption is influenced by the level of deprivation consistently with the distribution of diseases. For this reason, the main levers on which it is necessary to act to reduce disparities in health status are mainly related to prevention. Moreover, it is worth pointing out that the use of a municipal deprivation indicator necessarily generates an ecological bias, however, the experience of the present study, which for the first-time deals with the complex and delicate issue of equity in Italian pharmaceutical assistance, sets the stage for new insights that could overcome the limits.

The diagnosis and clinical management of the neuropsychiatric manifestations of lupus.

Neuropsychiatric (NP) involvement in Systemic Lupus Erythematosus (SLE), can be a severe and troubling manifestation of the disease that heavily impacts patient's health, quality of life and disease outcome. It is one of the most complex expressions of SLE which can affect central, peripheral and autonomous nervous system. Complex interrelated pathogenetic mechanisms, including genetic factors, vasculopathy, vascular occlusion, neuroendocrine-immune imbalance, tissue and neuronal damage mediated by autoantibodies, inflammatory mediators, blood brain barrier dysfunction and direct neuronal cell death can be all involved. About NPSLE a number of issues are still matter of debate: from classification and burden of NPSLE to attribution and diagnosis. The role of neuroimaging and new methods of investigation still remain pivotal and rapidly evolving as well as is the increasing knowledge in the pathogenesis. Overall, two main pathogenetic pathways have been recognized yielding different clinical phenotypes: a predominant ischemic-vascular one involving large and small blood vessels, mediated by aPL, immune complexes and leuko-agglutination which it is manifested with more frequent focal NP clinical pictures and a predominantly inflammatory-neurotoxic one mediated by complement activation, increased permeability of the BBB, intrathecal migration of autoantibodies, local production of immune complexes and pro-inflammatory cytokines and other inflammatory mediators usually appearing as diffuse NP manifestations. In the attempt to depict a journey throughout NPSLE from diagnosis to a reasoned therapeutic approach, classification, epidemiology, attribution, risk factors, diagnostic challenges, neuroimaging techniques and pathogenesis will be considered in this narrative review based on the most relevant and recent published data.

Brain unidentified bright objects ("UBO") in systemic lupus erythematosus: sometimes they come back. A study of microembolism by cMRI and Transcranial Doppler ultrasound.

OBJECTIVES: The objectives of this report are to assess the occurrence of microembolic signals (MES) detected by transcranial Doppler ultrasound (TCD) in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (SLE) neuropsychiatric involvement, and to verify the correlation between MES, clinical characteristics, especially the patent foramen ovale (PFO), and the presence of punctuate T2-hyperintense white matter lesions (WMHLs) detected by conventional magnetic resonance imaging (cMRI). METHODS: A TCD registration to detect MES from the middle cerebral artery was carried out in SLE and NPSLE patients after exclusion of aortic and/or carotid atheromatous disease. In all patients conventional brain magnetic resonance imaging (cMRI) and transesophageal echocardiography were performed. Patients were stratified in two groups, with and without WMHLs, and compared. RESULTS: Twenty-three SLE patients (16 NPSLE and seven SLE) were enrolled in the study. Overall MES were detected in 12 patients (52.1%), WHMLs were detectable in 15 patients (13 NPSLE and two SLE) while eight patients had normal cMRI (three NPSLE and five SLE). Matching TCD ultrasound and neuroimaging data, MES were detected in 10 (nine NPSLE and one SLE) out of 15 patients with WHMLs and in only two out of eight patients (two NPSLE and six SLE) with normal cMRI, both with NP involvement. A PFO was confirmed in all cases of MES detection. CONCLUSION: MES are frequent findings in SLE patients, especially in those with focal WMHLs detected by cMRI and correlating with PFO. These findings should be taken into account and suggest caution in the interpretation of cMRI pictures along with a careful evaluation of MES in patients with cMRI abnormalities that should be included in the workup of SLE patients.

Vibrational signatures of the water behaviour upon confinement in nanoporous hydrogels.

The fundamental question of how the reorganization of the hydrogen-bond (HB) network of water is influenced by the combination of nano-confinement and hydrophobic/hydrophilic solvation effects is addressed here using a spectroscopic study of water absorbed in a model, pH-sensitive polysaccharide hydrogel. The effects of temperature, hydration level and pH on the vibrational dynamics associated with the water molecules and the polymer skeleton are disentangled and analysed by a complementary and combined use of UV-Raman scattering and IR spectroscopy. The experimental data give evidence that the solvation effects in the hydrogel matrix are essentially dominated by the hydration of more hydrophobic parts of the polymer network, while the effect of pH on the HB reorganization of confined water molecules is found to be similar to that induced by cooling of the system. A tentative explanation of these results has been provided in terms of interplay between different kinds of interactions, i.e. hydrophobic vs. hydrophilic.

Water and polymer dynamics in a model polysaccharide hydrogel: the role of hydrophobic/hydrophilic balance.

The molecular dynamics of water and a polymer matrix is here explored in a paradigmatic model of a polysaccharide hydrogel, by the combined use of UV Raman scattering and infrared measurements. The case example of cyclodextrin nanosponges (CDNS)/hydrogel is chosen since the simultaneous presence in the structure of the polymer matrix of both hydrophilic and hydrophobic sites mimics the complexity of polysaccharide hydrogels. In this way, the contributions provided by the balance between the hydrophilicity/hydrophobicity and the grade of entanglement of the polymer hydrogel to lead to the formation of the gel phase are separately accounted and evaluated. As main results, we found that the hydrophobic CH groups inserted on the aromatic ring of CDNS experience a more pronounced dynamic perturbation with respect to the carbonyl groups due to the collision between the solvent and vibrating atoms of the polymer. The overall results provide a detailed molecular picture of the swelling phenomena occurring when a chemically cross-linked polymer contacts with water or biological fluids and exploits the potentiality of UV Raman spectroscopy to retrieve dynamic information besides their structural counterpart obtained by the classical analysis of the basic features of vibrational spectra.

Combining Raman and infrared spectroscopy as a powerful tool for the structural elucidation of cyclodextrin-based polymeric hydrogels.

A detailed experimental and theoretical vibrational analysis of hydrogels of ß-cyclodextrin nanosponges (ß-CDNS), obtained by polymerization of ß-cyclodextrin (ß-CD) with the cross-linking agent ethylenediaminetetraacetic acid (EDTA), is reported here. Thorough structural characterization is achieved by exploiting the complementary selection rules of FTIR-ATR and Raman spectroscopies and by supporting the spectral assignments by DFT calculations of the spectral profiles. The combined analysis of the FTIR-ATR spectra of the polymers hydrated with H2O and D2O allowed us to isolate the HOH bending of water molecules not involved in symmetrical, tetrahedral environments. The analysis of the HOH bending mode was carried out as a function of temperature, showing the existence of a supercooled state of the water molecules. The highest level of cooperativity of the hydrogen bond scheme was reached at a value of the ß-CD/EDTA molar ratio n = 6. Finally, the connectivity pattern of "uncoupled" water molecules bound to the nanosponge backbone was found to be weakened by increasing T. The temperature above which the population of non-tetracoordinated water molecules becomes predominant turned out to be independent of the parameter n.

Probing the molecular connectivity of water confined in polymer hydrogels.

The molecular connectivity and the extent of hydrogen-bond patterns of water molecules confined in the polymer hydrogels, namely, cyclodextrin nanosponge hydrogels, are here investigated by using vibrational spectroscopy experiments. The proposed spectroscopic method exploits the combined analysis of the vibrational spectra of polymers hydrated with water and deuterated water, which allows us to separate and selectively investigate the temperature-evolution of the HOH bending mode of engaged water molecules and of the vibrational modes assigned to specific chemical groups of the polymer matrix involved in the physical interactions with water. As main results, we find a strong experimental evidence of a liquid-like behaviour of water molecules confined in the nano-cavities of hydrogel and we observe a characteristic destructuring effect on the hydrogen-bonds network of confined water induced by thermal motion. More interestingly, the extent of this temperature-disruptive effect is found to be selectively triggered by the cross-linking degree of the hydrogel matrix. These results give a more clear picture of the molecular mechanism of water confinement in the pores of nanosponge hydrogel and open the possibility to exploit the spectroscopic method here proposed as investigating tools for water-retaining soft materials.

How do the EMA and FDA decide which anticancer drugs make it to the market? A comparative qualitative study on decision makers' views.

BACKGROUND: The process leading to a regulatory outcome is guided by factors both related and unrelated to the data package, defined in this analysis as 'formal and informal factors', respectively. The aim of this qualitative study was to analyse which formal and informal factors drive the decision-making process of the European Medicines Agency (EMA) and Food and Drug Administration (FDA) regulators with regard to anticancer drugs, using in-depth semi-structured interviews with regulators of the two agencies. METHODS: In line with the theory and practice of qualitative research, no set sample size was defined a priori. Respondent enrolment continued until saturation and redundancy were reached. Data were collected through means of in-depth semi-structured interviews conducted either in a face-to-face setting or via Skype(®) with each regulator. The interviews were audio-recorded and verbatim transcribed. The analysis was manually carried out on the transcribed text. Data were independently coded and categorized by two researchers. Interpretation of the findings emerged through a process of triangulation between the two. RESULTS: Seven EMA and six FDA regulators, who had extensive experience with making decisions about anticancer medicines, were interviewed between April and June 2012. There is an open dialogue between the FDA and EMA, with the two moving closer and exchanging information, not opinions. Differences in decision-making between the agencies may be due to a different evaluation of end points. Different interaction modalities with industry and patients represent an additional source of divergence with a potential impact on decision-making. The key message of our respondents was that the agencies manage uncertainty in a different way: unlike the EMA, the FDA has a prevailing attitude to take risks in order to guarantee quicker access to new treatments. CONCLUSIONS: Although formal factors are the main drivers for regulatory decisions, the influence of informal factors plays an important role in the drug evaluation process.

Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis.

The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases. The literature published between 2008 and 2012 was systematically reviewed and updated recommendations on MTX use in rheumatic diseases, particularly RA, were formulated. These recommendations were approved by a panel of expert Italian Rheumatologists. A total of 10,238 references were identified, among which 70 studies were selected for critical evaluation. Sufficient evidence had accumulated to warrant changes to several of the recommendations in the new version. A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed.

Medication use in Italian nursing homes: preliminary results from the national monitoring system.

Background: The aging population has increased concerns about the affordability, quality, and nature of long-term care for older people, emphasizing the role of nursing homes. Unlike acute hospital and primary care, there is a lack of drug consumption data in long-term care to understand regional or national healthcare policies. Objectives: This study aimed to describe medication consumption by older adults and expenditure in Italian nursing homes (NHs). Methods: Data on drug consumption and costs from the administrative medicine informational flows that detect medicines packages supplied to patients in health facilities and NHs were used. Data on the characteristics of the healthcare residence were from the Italian Health Ministry. Records for the year 2019, selecting the nursing homes exclusively providing elderly or mixed (elderly and disabled) were used. Results: In 2019, the total expenditure on medicines in NHs amounted to 25.38 million euros, the average cost to 1.30 and the expenditure per bed to 436.18 euros. Cardiovascular drugs were the highest-consuming therapeutic class (177.0 defined daily doses-DDDs/100 days of NH stay; 22.2% of total) followed by drugs acting on the alimentary tract and metabolism (167.6% and 21.0%) and blood drugs (160.4% and 20.1%). The treatment of hypertension and heart failure was widely the most frequently used, with the consumption being driven mainly by furosemide and ramipril. Antiulcer drugs were used on average in more than half of the days of NH stay (58.5 DDDs/100 days of NH stay), representing a therapeutic category for which deprescribing initiatives are recommended. On average, almost all patients received a dose of benzodiazepines, antipsychotics and antidepressants (37.6, 35.9, and 17.7 DDDs/100 days of NH stay, respectively), confirming the high prevalence of use for these medicines. Antibiotics reached 6.8 DDDs/100 days of NH stay. Conclusion: The availability of data in this specific setting allows the identification of the main interventions toward improving appropriateness and represents a challenge for drug utilization research. Data from this study suggest that proton pump inhibitors (PPIs), benzodiazepines and antibacterials can be areas of improving prescribing appropriateness.

Pregnancy in patients with undifferentiated connective tissue disease: a prospective case-control study.

OBJECTIVES: To assess the outcome of pregnancy and disease flare or differentiation into well-defined connective tissue disease (CTD), in a cohort of pregnant patients with undifferentiated connective tissue disease (UCTD) and to compare these findings with those obtained from a population of non-pregnant women with UCTD. METHODS: In total, 55 pregnancies (in 50 UCTD patients) were monitored from the positive pregnancy test until the sixth month after delivery. Likewise, during a 15-month timeframe, the incidence of flares or evolution into a major CTD was also recorded in a population of 53 non-pregnant women with UCTD. The Student t-test was applied for unpaired, continuous variables and chi-square was applied when percentages were compared. RESULTS: The mean duration of the successful pregnancies was 38.6 weeks (range 28-42) while the mean birth weight was 3190 g (range 1200-4600 g). Three pregnancies (5.4%) ended in miscarriage. The following obstetric complications were found: five premature membrane ruptures, two preeclampsia and two intra-uterine growth restrictions. In a total of 16 patients (32%) the disease flared during pregnancy or during the 6-month post-delivery period. Of these, five developed well-defined CTD after delivery. In the control population, six patients flared (11%) and, of these, only one developed a well-defined CTD. CONCLUSIONS: If pregnancy is properly treated, the outcome in UCTD patients is generally good while, considering disease activity, pregnancy appears to be a clear risk factor for flare up or evolution into well-defined CTD.

GISEA: an Italian biological agents registry in rheumatology.

The GISEA registry is an independent database that was established by the Italian Group for the Study of Early Arthritis (GISEA) in 2008, funded by the Italian Association of Rheumatic Patients (ANMAR - ONLUS). In line with the network's epidemiological strategy, the initial protocol was designed to collect long-term follow-up data concerning patients with rheumatic diseases treated with biological agents in order to investigate the realworld characteristics in terms of disease activity, comorbidities and survival on treatment. We here describe the design and methodology used to collect patient data. Information concerning demographics, disease activity, treatment changes (including the reasons for changing and the duration of each therapy), concomitant therapies and adverse events is available to all the members of the study groups by means of a web-based interface that allows queries and the presentation of numerical data, as well as graphics to illustrate trends. Fourteen Italian rheumatology centres have contributed patients to the database which, at the time writing, includes 5145 patients (72% women) with a mean age of 53 years (range 16-88). The initial diagnoses were rheumatoid arthritis (3494 patients, 67.9%), psoriatic arthritis (833, 16.2%), ankylosing spondylitis (493, 9.6%), undifferentiated spondylo-arthritides (307, 5.9%), enteropathic arthritis (14, 0.3%) and spondylitis following reactive arthritis (4, 0.1%). These patients have been followed for up to 10 years, and 1927 (35.8%) have been treated for at least three years. The biological treatments received include etanercept, infliximab, anakinra, adalimumab, abatacept, rituximab and tocilizumab. A total of 2926 adverse events have been observed, with 1171 patients (22%) reporting at least one. Analysis of the accumulated data will provide insights into the critical early phase of the studied arthritides, and enable us to identify the clinical and laboratory profiles that may predict responsiveness to a specific therapy.

Starting dose and dose adjustment of non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation.

This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with atrial fibrillation (AF). In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. During the reference period, treatment was commenced for 866,539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA2DS2-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

[Italian consensus on the recommendations about the use of methotrexate for the treatment of rheumatic diseases with a focus on rheumatoid arthritis: results from the "3E initiative"]. / Consensus italiana sulle raccomandazioni per l'utilizzo del methotrexate nelle malattie reumatiche con focus sull'artrite reumatoide: i risultati della "3E initiative".

OBJECTIVE: To develop a set of national evidence-based recommendations for the use of Methotrexate (MTX) in daily clinical practice. METHODS: A panel of 37 Italian Rheumatologists reviewed 10 international recommendations formulated during the "3E (Evidence, Expertise, Exchange) initiative" for the year 2007-8, following a systematic literature search in Medline, Embase, Cochrane Library, and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts and the revision of selected papers and the appraisal of Oxford levels of evidence. Moreover, the same panel by the same methodology formulated further 5 recommendations on topics previously selected by Italian representatives to 3E initiative. The agreement about the set of proposed recommendations was stated by a consensus process and the potential impact on clinical practice was assessed. RESULTS: International Recommendations were analysed and changed when appropriate. In addition, 5 national recommendations were developed by identifying 6371 references, selecting and evaluating the 29 ones satisfying Evidence Based Medicine principles. CONCLUSIONS: A set of 15 national recommendations for the use of MTX in daily clinical practice was developed. These recommendations are evidence-based and integrate the expertise of a large panel of Italian rheumatologists.

Non-vitamin K antagonist oral anticoagulation agents in patients with atrial fibrillation: Insights from Italian monitoring registries.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased risk of stroke and thromboembolism. Anticoagulation with Vitamin K antagonists (VKAs) or with novel oral anti-coagulants (NOACs) represents the cornerstone of the pharmacological treatment to reduce the risk of thromboembolism. This study aims to provide real-world data from a whole large European country about NOAC use in "non-valvular atrial fibrillation" (NVAF). METHODS: We analysed the Italian Medicines Agency (AIFA) monitoring registries collecting data of a nationwide cohort of patients with "NVAF" treated with NOACs. Using logistic regression analysis, baseline characteristics and treatment discontinuation information were compared among initiators of the 4 NOACs. RESULTS: In the reference period, the NOAC database collected data for 683,172 patients. The median age was 78 years with 19.5% aged 85 or older. Overall, the treatments were in accordance with guidelines. About 1/3 of patients switched from a prior VKA treatment; in the 72.3% of cases, these patients had a labile International Normalized Ratio (INR) at first prescription. The most prescribed NOAC was rivaroxaban, followed by apixaban, dabigatran and edoxaban. CONCLUSIONS: This study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data.

Sustained remission of SAPHO syndrome with pamidronate: a follow-up of fourteen cases and a review of the literature.

OBJECTIVE: To evaluate the efficacy of intravenous (i.v.) pamidronate in patients with SAPHO syndrome refractory to first line treatments and to review the available literature on pamidronate for this indication. METHODS: We report 14 cases of SAPHO syndrome refractory to non-steroideal anti-inflammatory drugs (NSAIDs), glucocorticoids and disease modifying anti-rheumatic drugs (DMARDs) treated with i.v. pamidronate. All patients received i.v. 60 mg pamidronate/day for 3 consecutive days. The primary evaluation criterion was the disappearance of bone pain, considered as the reduction in the visual analogic scale for pain (VAS) greater than 50%. RESULTS: Ten patients were females and 4 were males. The mean age at onset was 40.4 years old. Ten patients presented a relapsing-remitting course, while in 4 cases the disease followed a prolonged course. In all cases anterior chest wall involvement occurred early in the disease. In 2 cases there was also a peripheral monoarthritis. Eleven patients experienced several flares of palmo-plantar pustulosis, while severe acne was present in 2. In one case there was no cutaneous involvement. Twelve of the 14 patients had a good response after 3 infusions and in 8 of these patients a sustained remission was observed. The recurrence of skin manifestations does not seem to be influenced by pamidronate. CONCLUSIONS: Pamidronate appears to be an effective treatment in the osteo-articular manifestations of SAPHO syndrome. As far as cutaneous lesions are concerned, evidence of efficacy is not so impressive.

Visceral leishmaniasis and anti-TNF-alpha therapy: case report and review of the literature.

OBJECTIVES: Visceral leishmaniasis (VL) is an extremely rare example of opportunistic infection in patients treated with TNF-alpha antagonists and only a few cases have been described. In this paper risk factors, clinical features, diagnostic work-up and outcome of patients developing VL under biologic therapy are described. METHODS: Case report and review of the published cases of VL in patients under biologic treatment. RESULTS: We retrieved six patients, including ours, all of whom presented anarchic fever and pancytopenia. In 5 cases, splenomegaly was detected. The same number of patients came from endemic areas for VL. In the majority of the cases a bone marrow examination was not diagnostic, requiring the performance of a second one and/or the execution of other diagnostic tests. One fatal outcome was observed. CONCLUSION: Even if VL represents a sporadic complication of biologic treatments, its presence should always be suspected in patients developing a triad of signs and symptoms constituted by fluctuant fever, pancytopenia and splenomegaly, especially if coming from endemic areas. In these cases an extensive diagnostic work-up must be warranted. Atypical and confusing features may resemble autoimmune diseases at presentation and during the course of the illness.

Combination treatment with etanercept and an intensive spa rehabilitation program in active ankylosing spondylitis.

The aim of this study is to determine the effects of a combination treatment with etanercept and spa rehabilitation versus etanercept alone on function, disability and quality of life in a group of patients with active ankylosing spondylitis (AS). Sixty patients with AS underwent etanercept as suggested by ASAS/EULAR recommendations. As the clinical and laboratory conditions improved, 30 patients accepted the proposal of coupling the medical therapy with a 7-day rehabilitation program in a thermal baths centre; the remaining 30 subjects continued to take the biologic agent alone. The comparisons between the 2 groups were made after 3 and 6 months. The primary outcome was an improvement in BASFI. The secondary outcome was an improvement in the visual analogic scale of EuroQol (EQ-5Dvas). After 6 months a statistically significant improvement in BASFI (p < 0.05) and EQ-5DVAS (p < 0.05) scores was observed in both groups. The mean change in EQ-5DVAS value showed a statistically significant difference in favour of the combination therapy group versus the monotherapy group (22 vs 32, p < 0.05). A therapeutic regimen combining etanercept with an intensive rehabilitation program contributes to disability reduction and ameliorates quality of life for AS patients.