The Rheumatology drugs for COVID-19 management: Which and when?

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. 'Repurposing' immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patient

Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations on the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and one month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. Although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Acute and chronic pain in orthopaedic and rheumatologic diseases: mechanisms and characteristics

Pain is one of the most frequent clinical symptoms encountered by orthopaedic surgeons and rheumatologists as it is one of the main reasons for patients seeking medical help. Traumas and/or inflammatory rheumatologic diseases give rise to two different types of acute pain, but their chronic evolution is so similar that they both need to be treated as early as possible. It is now widely accepted that chronic pain is a disease per se, and that its location may be less important than the way in which it is perceived by people suffering from it. Consequently, its pharmacological and non-pharmacological treatment should be based on its specific characteristics, other disease-related factors, the ability of patients to cope with it, and the way in which they live their lives

Infections in rheumatoid arthritis

PURPOSE OF REVIEW: The purpose of this review is to provide an update concerning recent advances in the evidence- based study of serious infections in patients with rheumatoid arthritis (RA) treated with biological drugs or conventional disease-modifying antirheumatic drugs (DMARDs), concentrating on studies published in the last 18 months. RECENT FINDINGS: New studies have further strengthened existing evidence relating the use of biological drugs to serious infections. The risk does not seem to be any different with short-term or long-term use. There is still a lack of conclusive studies identifying biomarkers, but it is plausible that the drugs have direct effects on cytokines and cell activity and then serious infections. SUMMARY: The frequent infections of patients with RA may be due to the disease itself (altered immunological function, disability, immobility, joint surgery), extra-articular manifestations or DMARDs, immunosuppressants and steroids. The use of biological drugs lead to the development of serious infections including tuberculosis. Patients should be informed of their increased risk, and physicians need to be aware of these complications and how to treat them

What are the dangers of biological therapy discontinuation or dose reduction strategies when treating rheumatoid arthritis?

Introduction: Treatment with biological DMARDs (bDMARDs) has meant that remission or low disease activity (LDA) is now a realistic goal for patients with rheumatoid arthritis (RA). However, as in the case of all long-term therapies, potential side-effects give rise to concern. The main reasons for withdrawing or tapering bDMARDs are safety and the sustainability of national healthcare systems. Given these data our review has been focused on important question: whether conventional, including steroids, or bDMARDs can be reduced or even stopped in patients with stable established RA or early RA. Areas covered: The studies included in the evaluation had to be RCTs, observational studies, systematic reviews evaluating the withdrawing or tapering bDMARDs in RA patients who have been on long-term treatment and have achieved remission or LDA. A search was made in the MEDLINE and EMBASE databases from 1980 to May 2016. Expert commentary: There is curently no standardised way of identifying the patients for whom reducing bDMARD therapy is appropriate. Clinical experience and data from de-escalation studies suggest that patients with RA in sustained remission are the best target population for studying drug-tapering regimens, and that LDA should not be considered an adequate indication for bDMARD de-escalation because it could hide a persistent amount of inflammation

Effect of biological DMARDs and JAK inhibitors in pain of chronic inflammatory arthritis

Introduction: The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs) and, more recently, of Janus kinase inhibitors (JAKi) has had a major impact on the long-term outcomes of chronic inflammatory arthritis (IA). However, the persistence of pain, even in patients with a complete pharmacological control of peripheral inflammation, represents an important clinical challenge in the treatment of IA. Areas covered: In this review, we provide an overview of possible mechanisms underlying pain in IA and its assessment, as well as the effects of bDMARDs and JAKi on pain management. Expert opinion: The overall data showed a good effect of bDMARDs and JAKi on pain, more pronounced for JAKi. However, it is challenging to distinguish the effect on the different types of pain (nociceptive, neuropathic, and nociplastic)

Controlled-release pregabalin in the treatment of fibromyalgia

Introduction: Fibromyalgia (FM) is a chronic disorder whose symptoms of musculo-skeletal pain, fatigue, sleep disturbances, and cognitive impairment pervade the personal, occupational, and social aspects of a patient’s life. Together with the antidepressants duloxetine and milnacipran, the anticonvulsant pregabalin (PGB) is one of the three drugs approved by the Food and Drug Administration for the treatment of FM. The aim of this narrative review is to summarize the data relating to the efficacy and safety of the controlled-release formulation of PGB (PGB-CR) in patients with FM. Areas covered: Efforts by the pharmaceutical industry have led to the introduction of new formulations of already approved drugs to enhance treatment convenience and adherence. Expert opinion: Although there are no published studies specifically comparing PGB-CR and PGB-IR formulations in FM patients, the efficacy and safety profiles of PGB-CR seem to be similar to those of the IR formulation, and the convenience of once-daily dosing potentially enhances patient compliance. However, the amount of evidence is not sufficient to draw any definite conclusions, and further studies of larger patient samples are needed

Impaired lung transfer factor in fibromyalgia syndrome

none8noForty-five consecutive anti-nuclear antibody (ANA)-negative female Caucasian patients aged 50.1± 5.6 years with FM and compared with 45 healthy female control volunteers matched in terms of age and body mass index (BMI). The autonomic function has been evaluated by means of standard electrocardiography (ECG), finger blood pressure respiration, and muscle sympathetic nerve activity (MSNA) at rest and during a stepwise tilt test up to 75°. Their autonomic profiles were drawn up on the basis of MSNA, plasma catecholamine levels, and spectral indices of cardiac sympathetic and vagal modulation, and sympathetic vasomotor control computed by means of the spectrum analysis of RR and systolic arterial pressure (SAP) variability. Lung volumes and dynamic spirometry parameters were assessed by means of plethysmography. All of the patients were clinically evaluated and completed the FQI and COMPASS questionnaire. There was no difference in lung volumes between the FM patients and healthy controls, but DLCO (83±4 vs. 96±5; p<0.001), Kco (84±5 vs 98±5; p<0.001), DM (12.7±2.4 vs 13.6±1.8; p<0.05) and Vc (48±3.9 vs 65±7; p<0.001) were significantly reduced in the patients. The COMPASS-31, RCS and pain VAS scores significantly correlated with DLCO, Kco and Vc with the correlation being particularly close in the case of Vc. Furthermore, univariate Cox proportional hazard analysis showed that the three scores were all significantly associated with an increased risk of impaired DLCO (respectively, χ(2) 16.21, p<0.0005; χ(2) 7.09, p<0.005; χ(2) 6.37, p<0.01). FM impairs DLCO mainly as a result of a reduction in Vc, and that this defect is inversely proportional to the severity of the dysfunction suggesting a relationship between impaired DLCO and autonomic nerve dysfunctionRizzi, M; Atzeni, F; Airoldi, A; Masala, If; Frassanito, F; Salaffi, F; Macaluso, C; Sarzi-Puttini, PRizzi, M; Atzeni, F; Airoldi, A; Masala, If; Frassanito, F; Salaffi, Fausto; Macaluso, C; Sarzi Puttini, P