JANUS KINASE ENZYME (JAK) INHIBITORS AND RHEUMATOID ARTHRITIS: A REVIEW OF THE LITERATURE

Cytokines play an essential role in normal cell growth and the regulation of immune function. The emergence of Janus Kinase Enzyme inhibitors promises the start of a revolution in the treatment of several chronic diseases. Their efficacy and safety profile have been demonstrated in multiple trials and they have been licensed for the treatment of a number of diseases including RA and PsA. Moreover, the use of highly selective Janus Kinase Enzyme inhibitors is currently being studied aiming to reduce side effects compared with traditional JAKinibs, an example of that would be the recent FDA approved upadacitinib. The Janus Kinase Enzyme inhibitorsmay supplant the classical biologic agents in the treatment of autoimmune diseases, since they exhibitthe advantages of oral administration, simultaneous blockade of multiple cytokines, reversibility and the lack of immunogenicity

Exploring the efficacy and safety of cannabis in the management of fibromyalgia

© 2022 The Authors. Published by Innovare Academic Sciences. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.22159/ijcpr.2022v14i1.44109Fibromyalgia is a chronic health condition characterized by chronic pain fatigue, sleep disturbances and many other symptoms affecting a patient’s quality of life. Patients with fibromyalgia often visit rheumatology outpatients with a long list of symptoms and often receive multiple medications. Many have seen multiple specialists and have done a lot of reading about alternative modalities of treatment. The limited effectiveness of conventional therapy coupled with widespread media attention raises the question of cannabis use. This review examines the literature on cannabinoid use in fibromyalgia against the context of the international variation in legal frameworks, the available products and the outcomes reported. A detailed review was performed using the EMBASE and PUBMED databases. It was concluded that despite the interest in the use of cannabinoids in the management of fibromyalgia, there is insufficient evidence to prescribe the currently available licensed medicines or to recommend the complementary health products available for legal purchase. There is a need for more global clinical randomised trials to accurately determine medicinal cannabis short and long-term long efficacy and safety for its acute and chronic use

Baricitinib in rheumatoid arthritis – real world cross-sectional study

© 2020 The Authors. Published by Bentham Open. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: 10.2174/1874312902014010028Introduction: Rheumatoid arthritis (RA) is the most common cause of inflammatory polyarthritis. In RA, increased circulating levels of pro-inflammatory cytokines contribute to the overall symptomatology of fatigue, pain, and joint stiffness. Baricitinib is an orally administered biologic DMARD, used in RA patients, inhibiting signaling via JAK1/JAK2 inhibition, reducing the release of pro-inflammatory cytokines. Objective: To explore the efficacy and tolerability for baricitinib in a local population. Methods: A cross-sectional study was carried out to review data of RA patients on Baricitinib from the researchers’ own clinic, since its approval in August 2017. The data was collected from an anonymized electronic patient records report. The clinical response was then classified into mild, moderate, and significant improvement. Results and Discussion: Overall, 27 out of 37 patients (72.9%) showed clinical improvement with baricitinib. In 9(24.3%) out of 37 patients, the dose had to be reduced to either 2mg/day or 2mg/day - 4mg/day on alternate days. In four of the 9 patients’ where the dose was reduced due to infections (UTI or sinuses), they subsequently experienced fewer infections while maintaining moderate improvement in their RA. Conclusion: There is a need for longer-term and larger studies to evaluate the full side effects profile of baricitinib in the local population

Janus kinase enzyme (JAK) inhibitors and rheumatoid arthritis: a review of the literature

Cytokines play an essential role in normal cell growth and the regulation of immune function. The emergence of Janus Kinase Enzyme inhibitors promises the start of a revolution in the treatment of several chronic diseases. Their efficacy and safety profile have been demonstrated in multiple trials and they have been licensed for the treatment of a number of diseases including RA and PsA. Moreover, the use of highly selective Janus Kinase Enzyme inhibitors is currently being studied aiming to reduce side effects compared with traditional JAKinibs, an example of that would be the recent FDA approved upadacitinib. The Janus Kinase Enzyme inhibitorsmay supplant the classical biologic agents in the treatment of autoimmune diseases, since they exhibitthe advantages of oral administration, simultaneous blockade of multiple cytokines, reversibility and the lack of immunogenicity

Management of fatigue – a narrative review of proposed interventions and their effectiveness

© 2001 The Author. Published by International Journal of Current Research. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://www.journalcra.com/article/management-fatigue-%E2%80%93-narrative-review-proposed-interventions-and-their-effectivenessIntroduction: Fatigue is a significant and frequently encountered health complaint that may accompany many medical conditions, communicable and non-communicable. Long-Covid is increasingly presenting to general practice and specialist neurology and rheumatology clinics which in most cases involves elements of CFS causing sudden increase in the patients seeking solutions for chronic fatigue. Results: There are many supplements offered commercially for the treatment of fatigue. Some are categorised as complementary or traditional medicines and are not licensed or controlled as medicinal products. Of those licensed as medicines, many are not licenced for the treatment of fatigue, so are prescribed ‘off-label.’ Patients have reported variable experiences with the different supplements and medications discussed. This paper attempts to document the available evidence for their efficacy in the treatment of fatigue. Conclusion: In almost all cases, only some patients derive any benefit and the benefits found are marginal culture RCT comparative studies using standardised products from those listed in this review are required to be able to make a definitive conclusion

Dual energy computed tomography in gout: our experience

© 2021 The Authors. Published by Radiance Research Academy. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.31782/IJCRR.2021.131432Introduction: Gout is a common medical problem, affecting at least 1% of men in Western countries, with a male: female ratio ranging from 7:1 to 9:1. For many patients, traditional investigations can be inconclusive. Dual Energy Computed Tomography (DECT) is emerging as a valuable tool for non-invasive confirmation of urate deposits in painful joints. Aim: To establish the effectiveness of the DECT in the identification of gout in patients with complex presentations where the diagnosis is not clear. Method: DECT at 140 kV and 80kV was used to image patients where the clinical diagnosis was unclear Results: Seven case studies are presented where an unclear clinical presentation was successfully diagnosed with the use of DECT. Conclusion: In a specialist tertiary referral centre, treating many patients whose presentation is atypical, DECT has become a valuable tool in confirming the presence or absence of gouty arthritis, in difficult cases with a diagnostic dilemmaPublished versio

Effect of anti-TNF and conventional synthetic disease-modifying anti-rheumatic drug treatment on work disability and clinical outcome in a multicentre observational cohort study of psoriatic arthritis

OBJECTIVE: To determine the effect of medical treatment on work disability in patients with active PsA in a real-world setting.METHODS: Four hundred patients with active PsA commencing or switching to anti-TNF or conventional synthetic DMARD (csDMARD) were recruited to a multicentre UK prospective observational cohort study. Work disability was measured using the work productivity and activity-specific health problem instrument and peripheral joint activity was measured with the disease activity in PsA composite measure.RESULTS: Four hundred patients were recruited, of whom 229 (57.25%) were working (of any age). Sixty-two patients of working age (24%) were unemployed. At 6 months there was a 10% improvement in presenteeism (P = 0.007) and a 15% improvement in work productivity (P = 0.001) among working patients commenced on csDMARDs (n = 164) vs a larger and more rapid 30% improvement in presenteeism (P &lt; 0.001) and 40% improvement in work productivity (P &lt; 0.001) among those commenced on anti-TNF therapy (n = 65). Clinical response was poor among patients commenced on a csDMARD (n = 272), with an 8.4 point improvement in disease activity in PsA (P &lt; 0.001) vs those commenced on anti-TNF therapy (n = 121), who had a 36.8 point improvement (P &lt; 0.001).CONCLUSION: We report significant and clinically meaningful improvements in both work disability and clinical outcomes after commencement of anti-TNF therapy in a real-world setting. Improvements in all outcomes among those commencing csDMARDs were slower and of a smaller magnitude.</p

Factors influencing work disability in psoriatic arthritis:first results from a large UK multicentre study

Objective. The aim of this study was to determine the extent to which structural damage, clinical disease activity, demographic and social factors are associated with work disability (WD) in PsA. Methods. Four hundred patients fulfilling CASPAR (Classification Criteria for Psoriatic Arthritis) criteria for PsA were recruited from 23 hospitals across the UK. Demographic, socio-economic, work, clinical and radiographic data were collected. WD was assessed with the Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire reporting WD as a percentage of absenteeism (work time missed), presenteeism (impairment at work/reduced effectiveness) and work productivity loss (overall work impairment/absenteeism plus presenteeism). Logistic and linear regressions were conducted to investigate associations with WD. Results. Two hundred and thirty-six participants of any age were in work. Absenteeism, presenteeism and productivity loss rates were 14% ( S.D . 29.0), 39% ( S.D . 27.2) and 46% ( S.D . 30.4), respectively. Ninety-two (26%) participants of working age were unemployed. Greater age, disease duration of 2–5 years and worse physical function were associated with unemployment. Patients reported that employer awareness and helpfulness exerted a strongly positive influence on remaining in employment. Higher levels of global and joint-specific disease activity and worse physical function were associated with greater levels of presenteeism and productivity loss among those who remained in work. Conclusion. Reduced effectiveness at work was associated with measures of disease activity, whereas unemployment, considered the endpoint of WD, was associated with employer factors, age and disease duration. A longitudinal study is under way to determine whether treatment to reduce disease activity ameliorates WD in the real-world setting

Real-world effectiveness and safety of SDZ ETN, an etanercept biosimilar, in patients with rheumatic diseases: final results from multi-country COMPACT study

[Abstract] Introduction: COMPACT, a non-interventional study, evaluated the persistence, effectiveness, safety and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA), axial-spondyloarthritis (axSpA) or psoriatic arthritis (PsA) treated with SDZ ETN (etanercept [ETN] biosimilar) in Europe and Canada. Methods: Patients (aged ≥ 18 years) who have been treated with SDZ ETN were categorised on the basis of prior treatment status (groups A-D): patients in clinical remission or with low disease activity under treatment with reference ETN or biosimilar ETN and switched to SDZ ETN; patients who received non-ETN targeted therapies and switched to SDZ ETN; biologic-naïve patients who started SDZ ETN after conventional therapy failure; or disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA considered suitable for treatment initiation with a biologic and started on treatment with SDZ ETN. The primary endpoint was drug persistence, defined as time from study enrolment until discontinuation of SDZ ETN treatment. Results: Of the 1466 patients recruited, 844 (57.6%) had RA, 334 (22.8%) had axSpA and 288 (19.6%) had PsA. Patients had an ongoing SDZ ETN treatment at the time of enrolment for an observed average of 138 days (range 1-841); 22.7% of patients discontinued SDZ ETN through 12 months of study observation. Overall, all the patients receiving SDZ ETN showed good treatment persistence at 12 months with discontinuation rates of 15.2%, 25.7% and 27.8% in groups A, B and C, respectively. Across all patient groups, no major differences were observed in the disease activity and PRO scores between baseline and month 12. Injection-site reactions were low across the treatment groups. Conclusion: These results support the effectiveness and safety of SDZ ETN treatment in patients with RA, axSpA or PsA in real-life conditions. The treatment persistence rates observed were consistent with previously published reports of patients treated with reference or other biosimilar ETN. No new safety signals were identified

Cytokines and inflammatory mediators: 25. Certolizumab Pegol has a Different Profile from the other Anti-TNFS, Including Golimumab, in a Variety of in Vitro Assays

Background: Activities of the anti-TNFs, certolizumab pegol (CZP), etanercept (ETA), infliximab (IFX) and adalimumab (ADA), have been compared in a range of in vitro assays. CZP is the only licensed PEGylated Fab' anti-TNF; ETA is a fusion protein with an IgG1 Fc, and IFX and ADA are both antibodies with an IgG1 Fc. Golimumab (GLM) is a monoclonal IgG1 TNF inhibitor recently approved for a number of indications; it is thus of interest to assess the in vitro activity of GLM. In vitro assays previously used were neutralisation of TNF in the L929 bioassay, inhibition of LPS-driven cytokine production by monocytes, induction of apoptosis in activated lymphocytes and monocytes, and induction of neutrophil necrosis. Methods: Neutralisation of human TNF was assessed in the L929 bioassay using a range of concentrations of the anti-TNFs and a fixed concentration of TNF (100 pg/mL). Activity of the anti-TNFs at inhibiting LPS-driven IL-1β secretion by monocytes was assessed by incubating peripheral blood monocytes with various concentrations of the anti-TNF for 1 hour (hr) and then washing the cells. LPS was added for 4 hrs, the supernatants collected and the IL-1β level measured by ELISA. To assess induction of apoptosis, peripheral blood lymphocytes were activated for 2 days with 2 μg/mL CD3/CD28 and monocytes with 300 U/mL IL-4 and GMCSF for 3 days. The effect of the anti-TNFs on apoptosis was assessed by Annexin V staining using flow cytometry 24 hrs later. The effect of the anti-TNFs on neutrophil necrosis was determined by measuring myeloperoxidase release after 12 hrs. An isotype-matched control was used in all assays except the L929 bioassay. Results: IC90 neutralisation activity of the anti-TNFs in the L929 bioassay was 0.3 ng/mL for ETA, 4 ng/mL for GLM, 15 ng/mL for ADA, and 20 ng/mL for IFX, compared with 2.5 ng/mL for CZP. CZP was the most potent inhibitor of LPS-driven IL-1β secretion (IC50 ∼0.1 ng/mL), followed by GLM (20 ng/mL) and IFX (50 ng/mL). GLM, ADA, IFX and ETA induced apoptosis of monocytes and lymphocytes to a similar degree reaching a level of 23% and ∼40% at 100 μg/mL, respectively. CZP caused no increase in apoptosis above the levels seen with the isotype-matched control. In the neutrophil necrosis assay, ADA,IFX and GLM caused ∼70% necrosis at 100 μg/mL, and ETA 48%. CZP did not increase the level of necrosis above the level of the control. Conclusions: Bioactivity of the IgG1 molecules GLM, IFX and ADA in neutralising human TNF was inferior to that of CZP and ETA. CZP, the only PEGylated anti-TNF, had a different profile to the other anti-TNFs as it was the most potent at inhibiting LPS-driven IL-1β production by monocytes, did not induce apoptosis of activated monocytes and lymphocytes, and did not cause neutrophil necrosis. The clinical relevance of these in vitro effects is unknown. Nevertheless, these assays show interesting in vitro differences between the anti-TNFs. Disclosure statement: G.F. and A.N. are employees of UC