Acupuncture as an alternative or in addition to conventional treatment for chronic non-specific low back pain: A systematic review and meta-analysis.

Background: Conventional therapies (CTs), pharmacological (PH) and non-pharmacological (NPH), do not always achieve benefits in the treatment of chronic low back pain (CLBP). We assessed efficacy and safety of acupuncture for CLBP as alternative or addition to CT. Methods: We included randomised controlled trials (RCTs) comparing acupuncture alone or in combination with CT to CT. We searched Medline, Cochrane Library, Embase up to May 2022. We assessed risk of bias with the original Cochrane tool and GRADE certainty of evidence. Results were pooled through meta-analysis. Results: Ten RCTs (2122 participants) were included comparing acupuncture versus CT and 4 RCTs (374 participants) were comparing acupuncture plus CT to CT alone. In terms of comparing acupuncture with NPH or PH, no differences were found for pain and disability. Comparing acupuncture with PH and NPH combined, pain and disability were reduced (SMD=-0.50, 95% CI -0.62 to -0.37; SMD=-0.71, 95% CI -1.17 to -0.24). Comparing acupuncture plus NPH with NPH alone, pain and disability were reduced (SMD=-0.70, 95% CI -0.94 to -0.46; SMD=-0.95, 95% CI -1.36 to -0.54). Comparing acupuncture plus PH with PH alone, pain and disability were reduced (MD=-0.21, 95% CI -433.28 to -10.42; MD=-3.1, 95% CI -4.87 to -1.83). Comparing acupuncture plus combined treatment versus combined treatment alone, no differences were found in pain, while disability was reduced (MD=-3.40 95% CI -5.17 to -1.63). No studies assessed adverse event. Certainty of evidence ranged from moderate to very low. Conclusions: We are uncertain whether acupuncture is more effective and safer than CT. In the comparisons without estimates' imprecision, acupuncture showed promising results. Acupuncture could be an option based on patients' preferences.

Chronobiology and Chronotherapy in Inflammatory Joint Diseases.

Circadian rhythm perturbations can impact the evolution of different conditions, including autoimmune diseases. This narrative review summarizes the current understanding of circadian biology in inflammatory joint diseases and discusses the potential application of chronotherapy. Proinflammatory cytokines are key players in the development and progression of rheumatoid arthritis (RA), regulating cell survival/apoptosis, differentiation, and proliferation. The production and secretion of inflammatory cytokines show a dependence on the human day-night cycle, resulting in changing cytokine plasma levels over 24 h. Moreover, beyond the circadian rhythm of cytokine secretion, disturbances in timekeeping mechanisms have been proposed in RA. Taking into consideration chronotherapy concepts, modified-release (MR) prednisone tablets have been introduced to counteract the negative effects of night-time peaks of proinflammatory cytokines. Low-dose MR prednisone seems to be able to improve the course of RA, reduce morning stiffness and morning serum levels of IL-6, and induce significant clinical benefits. Additionally, methotrexate (MTX) chronotherapy has been reported to be associated with a significant improvement in RA activity score. Similar effects have been described for polymyalgia rheumatica and gout, although the available literature is still limited. Growing knowledge of chronobiology applied to inflammatory joint diseases could stimulate the development of new drug strategies to treat patients in accordance with biological rhythms and minimize side effects.

Insulin Signaling in Arthritis.

Inflammatory arthritis is burdened by an increased risk of metabolic disorders. Cytokines and other mediators in inflammatory diseases lead to insulin resistance, diabetes and hyperlipidemia. Accumulating evidence in the field of immunometabolism suggests that the cause-effect relationship between arthritis and metabolic abnormalities might be bidirectional. Indeed, the immune response can be modulated by various factors such as environmental agents, bacterial products and hormones. Insulin is produced by pancreatic cells and regulates glucose, fat metabolism and cell growth. The action of insulin is mediated through the insulin receptor (IR), localized on the cellular membrane of hepatocytes, myocytes and adipocytes but also on the surface of T cells, macrophages, and dendritic cells. In murine models, the absence of IR in T-cells coincided with reduced cytokine production, proliferation, and migration. In macrophages, defective insulin signaling resulted in enhanced glycolysis affecting the responses to pathogens. In this review, we focalize on the bidirectional cause-effect relationship between impaired insulin signaling and arthritis analyzing how insulin signaling may be involved in the aberrant immune response implicated in arthritis and how inflammatory mediators affect insulin signaling. Finally, the effect of glucose-lowering agents on arthritis was summarized.

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP).

INTRODUCTION: Post-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs' reporting associated with biologics use in rheumatology. MATERIALS AND METHODS: We developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol. RESULTS: During the study period, 399 patients (245 females; mean age: 58 ± 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p < 0.0001). The most common AEs were injection site reactions and skin disorders. CONCLUSIONS: In conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology.

Old But Good: Modified-Release Prednisone in Rheumatoid Arthritis.

BACKGROUND: Since more than 50 years glucocorticoids represent the milestone in the treatment of inflammatory diseases, including rheumatoid arthritis (RA). However, many patients with RA present a circadian rhythm in symptoms severity with a significant worsening in the morning, that correlates with cyclic changes in circulating hormones and cytokines. Classical steroid therapy given in the morning fails to intercept this pathophysiological phenomenon. In the last years, a novel formulation of prednisone has been developed in order to better fit these variations, improve efficacy and minimize adverse events (chronotherapy). This modified-release (MR) prednisone is administered in the evening at 10.00 p.m. and absorbed after about 4 hours. METHODS: In this article, we reviewed the recent clinical trials evaluating the efficacy of MR prednisone in RA patients, including two randomized controlled double-blind clinical trials Circadian Administration of Prednisone in Rheumatoid Arthritis - 1 (CAPRA-1) and CAPRA-2 and other nonrandomized observational studies. RESULTS: According to the available evidence, MR prednisone seems effective in ameliorating morning stiffness in RA patients. CONCLUSION: In conclusion, the use of MR prednisone in the treatment regimen could be a costeffective choice in a significant proportion of RA patients, particularly in those with a clinical phenotype characterized by morning stiffness or morning recrudescence of pain. With regards to the safety, MR prednisone adverse events profile does not differ from that of IR glucocorticoids.