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International Ophthalmology Feb 2022To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the... (Review)
Review
PURPOSE
To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs.
METHODS
A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors' departments were examined.
RESULTS
Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin's lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to "bull's eye" maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment.
CONCLUSION
The level of evidence for most of the drug reactions described herein is restricted to the "likely" or "possible" rather than to the "certain" category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Glaucoma, Open-Angle; Humans; Iatrogenic Disease; Rituximab
PubMed: 34802085
DOI: 10.1007/s10792-021-02058-8 -
Clinical and Experimental Rheumatology May 2022Due to the rarity of relapsing polychondritis (RP), no randomised clinical trial has been conducted to date and treatment remains empirical. We performed a systematic... (Review)
Review
OBJECTIVES
Due to the rarity of relapsing polychondritis (RP), no randomised clinical trial has been conducted to date and treatment remains empirical. We performed a systematic literature review to assess the efficacy of the main conventional immunosuppressants and biotherapies used in RP.
METHODS
We searched MEDLINE for original articles without language restriction. Abstracts from American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) were also considered for inclusion. Observational studies and clinical trials reporting on the efficacy of conventional immunosuppressants and biotherapies in adult patients with RP were selected and pooled response rates for each treatment were computed.
RESULTS
Of 304 articles and abstracts identified, 31 underwent full-text review, and 11 were included. The studies involved a total of 177 patients, exposed to a total of 247 lines of treatments. The main treatments studied (by number of lines) were: TNF inhibitors (TNFi), n=92; methotrexate (MTX), n=38; tocilizumab (TCZ), n=26; anakinra (ANA), n=21; rituximab (RTX), n=16; abatacept (ABT), n=14; cyclophosphamide (CYC), n=14; azathioprine (AZA), n=13. The pooled response rates across studies were: 72% [95% CI: 42-95] for ABT, 66% [95% CI: 49-82] for TCZ, 64% [95% CI: 53-74] for TNFi, 56% [95% CI: 37-73] for MTX, 47% [95% CI: 26-68] for ANA, 43% [95% CI: 20-68] for RTX. Based on more limited data, response rates for AZA and CYC ranged from 38 to 100% and from 25 to 100%, respectively.
CONCLUSIONS
In this systematic review of available evidence regarding the treatment of relapsing polychondritis, ABT, TCZ and TNFi were the drugs associated with the best outcomes. ABT efficacy must be interpreted in light of the small number of patients treated. While MTX had slightly less efficacy, it is one of the drugs for which data are the most robust.
Topics: Abatacept; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Immunosuppressive Agents; Methotrexate; Polychondritis, Relapsing; Rituximab; Tumor Necrosis Factor Inhibitors
PubMed: 35238756
DOI: 10.55563/clinexprheumatol/h9gq1o -
Annals of the Rheumatic Diseases Jan 2023To update the evidence of non-biological treatments for axial spondyloarthritis (axSpA), as a basis for the 2022 Assessment of SpondyloArthritis international... (Review)
Review
Efficacy and safety of non-pharmacological and non-biological interventions: a systematic literature review informing the 2022 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis.
OBJECTIVE
To update the evidence of non-biological treatments for axial spondyloarthritis (axSpA), as a basis for the 2022 Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.
METHODS
A systematic literature review (2016-2021) on efficacy and safety of non-pharmacological and non-biological pharmacological treatments was performed, up to 1 January 2022. The research question was formulated according to the PICO format: Population: adult patients with r-axSpA and nr-axSpA; Intervention: non-pharmacological and non-biological pharmacological treatments; Comparator: active comparator or placebo; Outcomes: all relevant efficacy and safety outcomes. Type of studies included were: randomised controlled trials (RCTs), observational studies (for efficacy of non-pharmacological treatments, and safety), qualitative studies. Cohen's effect size (ES) was calculated for non-pharmacological and risk ratio (RR) for pharmacological treatments.
RESULTS
Of 107 publications included, 63 addressed non-pharmacological interventions, including education (n=8) and exercise (n=20). The ES for education on disease activity, function, mobility was small to moderate (eg. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ES: 0.06-0.59). Exercise had moderate to high ES on these outcomes (eg.
BASDAI, ES
0.14-1.43). Six RCTs on targeted synthetic disease-modifying antirheumatic drugs (DMARDs) showed efficacy of tofacitinib, upadacitinib and filgotinib (phase 2 only) in r-axSpA (range RR vs placebo for ASAS20: 1.91-3.10), while apremilast and nilotinib were not efficacious. Studies on conventional synthetic DMARDs (n=3), non-steroidal anti-inflammatory drugs (NSAIDs, n=8) and other drugs (n=12) did not provide new evidence on efficacy/safety (efficacy of NSAIDs confirmed; limited efficacy of short-term glucocorticoids in one RCT).
CONCLUSIONS
Education, exercise and NSAIDs confirmed to be efficacious in axSpA. JAKi were proved efficacious in r-axSpA.
Topics: Adult; Humans; Spondylitis, Ankylosing; Spondylarthritis; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Axial Spondyloarthritis
PubMed: 36261247
DOI: 10.1136/ard-2022-223297 -
Frontiers in Endocrinology 2021Diabetes mellitus (DM) is an ensemble of metabolic conditions that have reached pandemic proportions worldwide. Pathology's multifactorial nature makes patient...
Diabetes mellitus (DM) is an ensemble of metabolic conditions that have reached pandemic proportions worldwide. Pathology's multifactorial nature makes patient management, including lifelong drug therapy and lifestyle modification, extremely challenging. Currently, there is growing evidence about the effectiveness of using herbal supplements in preventing and controlling DM. Curcumin is a bioactive component found , which exhibits several physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and anti-diabetic activities. For these reasons, our objective is to systematically review the effects of or curcumin on DM. Databases such as PUBMED and EMBASE were searched, and the final selection included sixteen studies that fulfilled the inclusion criteria. The results showed that curcumin's anti-diabetic activity might be due to its capacity to suppress oxidative stress and inflammatory process. Also, it significantly reduces fasting blood glucose, glycated hemoglobin, and body mass index. Nanocurcumin is also associated with a significant reduction in triglycerides, VLDL-c, total cholesterol, LDL-c, HDL-c, serum C reactive protein, and plasma malonaldehyde. Therefore, it can be considered in the therapeutic approach of patients with DM.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diabetes Mellitus; Humans
PubMed: 34012421
DOI: 10.3389/fendo.2021.669448 -
Annals of the Rheumatic Diseases Jan 2023To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations...
Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis.
OBJECTIVES
To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).
METHODS
This systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.
RESULTS
Of 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.
CONCLUSION
The results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.
Topics: Humans; Glucocorticoids; Rheumatology; Biological Products; Antirheumatic Agents; Arthritis, Rheumatoid; Methotrexate; Biosimilar Pharmaceuticals; Janus Kinase Inhibitors
PubMed: 36368906
DOI: 10.1136/ard-2022-223365 -
RMD Open Nov 2022To conduct a systematic literature review (SLR) on the screening and prophylaxis of opportunistic and chronic infections in autoimmune inflammatory rheumatic diseases... (Review)
Review
Systematic literature review informing the 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases.
OBJECTIVE
To conduct a systematic literature review (SLR) on the screening and prophylaxis of opportunistic and chronic infections in autoimmune inflammatory rheumatic diseases (AIIRD).
METHODS
SLR (inception-12/2021) based on the following search domains: (1) infectious agents, (2) AIIRD, (3) immunosuppressives/immunomodulators used in rheumatology, (4) screening terms and (5) prophylaxis terms. Articles were retrieved having the terms from (1) AND (2) AND (3) plus terms from (4) OR(5). Databases searched: PubMed, Embase and Cochrane Library.
EXCLUSION CRITERIA
studies on postoperative infections, paediatric AIIRD, COVID-19, vaccinations and non-Εnglish literature. Study quality was assessed with Newcastle-Ottawa scale for non-randomised controlled trials (RCTs), RoB-Cochrane for RCTs, AMSTAR2 for SLRs.
RESULTS
From 5641 studies were retrieved, 568 full-text articles were assessed for eligibility, with 194 articles finally included. For tuberculosis, tuberculin skin test (TST) is affected by treatment with glucocorticoids and conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and its performance is inferior to interferon gamma release assay (IGRA). Agreement between TST and IGRA is moderate to low. For hepatitis B virus (HBV): risk of reactivation is increased in patients positive for hepatitis B surface antigen. Anti-HBcore positive patients are at low risk for reactivation but should be monitored periodically with liver function tests and/or HBV-viral load. Risk for Hepatitis C reactivation is existing but low in patients treated with biological DMARDs. For , prophylaxis treatment should be considered in patients treated with prednisolone ≥15-30 mg/day for >2-4 weeks.
CONCLUSIONS
Different screening and prophylaxis approaches are described in the literature, partly determined by individual patient and disease characteristics.
Topics: Adult; Child; Humans; Antirheumatic Agents; COVID-19; Hepatitis B virus; Opportunistic Infections; Rheumatic Diseases
PubMed: 36323488
DOI: 10.1136/rmdopen-2022-002726 -
Annals of the Rheumatic Diseases Jan 2023To perform a systematic literature review (SLR) concerning the safety of synthetic(s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) to inform the... (Review)
Review
Safety of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis.
OBJECTIVES
To perform a systematic literature review (SLR) concerning the safety of synthetic(s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA).
METHODS
SLR of observational studies comparing safety outcomes of any DMARD with another intervention in RA. A comparator group was required for inclusion. For treatments yet without, or limited, registry data, randomised controlled trials (RCTs) were used.
RESULTS
Fifty-nine observational studies addressed the safety of DMARDs. Two studies (unclear risk of bias (RoB)) showed an increased risk of serious infections with bDMARDs compared with conventional synthetic (cs)DMARDs. Herpes zoster infections occurred more with JAKi than csDMARDs (adjusted HR (aHR): 3.66) and bDMARDs (aHR: 1.9-2.3) (four studies, two low RoB). The risk of malignancies was similar across bDMARDs (five studies) and with tofacitinib compared with bDMARDs (one study, low RoB). The risk of major adverse cardiovascular events (MACE) was similar with bDMARDs and tofacitinib (two studies, one low RoB). Thirty studies reported safety from RCTs, with one, designed to evaluate safety, showing that malignancies (HR (95% CI): 1.48 (1.04 to 2.09)) and MACE (HR (95% CI): 1.33 (0.91 to 1.94)) occurred numerically more frequently with tofacitinib (5 mg and 10 mg doses combined) than with TNFi in patients with cardiovascular risk factors. In this study, the risk of venous thromboembolism (VTE) was higher with tofacitinib 10 mg than with TNFi.
CONCLUSION
The safety profile of bDMARDs was further demonstrated. Whether the difference in incidence of malignancies, MACE and VTE between tofacitinib and TNFi applies to other JAKi needs further evaluation.
Topics: Humans; Venous Thromboembolism; Biological Products; Antirheumatic Agents; Arthritis, Rheumatoid; Neoplasms
PubMed: 36376026
DOI: 10.1136/ard-2022-223357 -
Arthritis Care & Research Aug 2023To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with...
OBJECTIVE
To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA).
METHODS
An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions.
CONCLUSION
This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.
Topics: Humans; United States; Rheumatology; Arthritis, Rheumatoid; Antirheumatic Agents; Diet; Exercise Therapy
PubMed: 37227116
DOI: 10.1002/acr.25117 -
Clinical Rheumatology Sep 2023Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality... (Review)
Review
Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality CPG recommendations, highlighting areas of consistency, and inconsistency. Electronic searches of five databases and four online guideline repositories were performed. RA management CPGs were eligible for inclusion if they were written in English and published between January 2015 and February 2022; focused on adults ≥ 18 years of age; met the criteria of a CPG as defined by the Institute of Medicine; and were rated as high quality on the Appraisal of Guidelines for Research and Evaluation II instrument. RA CPGs were excluded if they required additional payment to access; only addressed recommendations for the system/organization of care and did not include interventional management recommendations; and/or included other arthritic conditions. Of 27 CPGs identified, 13 CPGs met eligibility criteria and were included. Non-pharmacological care should include patient education, patient-centered care, shared decision-making, exercise, orthoses, and a multi-disciplinary approach to care. Pharmacological care should include conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), with methotrexate as the first-line choice. If monotherapy conventional synthetic DMARDs fail to achieve a treatment target, this should be followed by combination therapy conventional synthetic DMARDs (leflunomide, sulfasalazine, hydroxychloroquine), biologic DMARDS and targeted synthetic DMARDS. Management should also include monitoring, pre-treatment investigations and vaccinations, and screening for tuberculosis and hepatitis. Surgical care should be recommended if non-surgical care fails. This synthesis offers clear guidance of evidence-based RA care to healthcare providers. TRIAL REGISTRATION: The protocol for this review was registered with Open Science Framework ( https://doi.org/10.17605/OSF.IO/UB3Y7 ).
Topics: Adult; Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Hydroxychloroquine; Methotrexate; Sulfasalazine; Practice Guidelines as Topic
PubMed: 37291382
DOI: 10.1007/s10067-023-06654-0 -
Clinical Cardiology Jul 2021The cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout remains equivocal. Febuxostat had a better safety outcome compared with... (Meta-Analysis)
Meta-Analysis Review
The cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout remains equivocal. Febuxostat had a better safety outcome compared with allopurinol. In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2000 and April 4, 2021, without any language restrictions. We did a systematic review and meta-analysis of included clinical trials to evaluate the cardiovascular safety of febuxostat compared to allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios were calculated with random effects and were reported with corresponding 95% confidence intervals (CI). From 240 potentially relevant citations, 224 papers were excluded; 16 studies were ultimately included in the analysis. Febuxostat had a better safety outcome compared with allopurinol,which was the composite of urgent coronary revascularization (OR: 0.84, 95% CI: 0.77-0.90, p < .0001) and stroke (OR: 0.87, 95% CI: 0.79-0.97, p = .009). However, that difference was not found in nonfatal myocardial infarction (OR: 0.99, 95% CI: 0.80-1.22, p = .91), cardiovascular related mortality (OR: 0.98, 95% CI: 0.69-1.38, p = .89) and all-cause mortality (OR: 0.93, 95% CI: 0.75-1.15, p = .52). No significant differences in cardiovascular related mortality and all-cause mortality were observed across any subgroup. This meta-analysis adds new evidence regarding the cardiovascular safety of febuxostat in patients. Initiation of febuxostat in patients was not associated with an increased risk of death or serious cardiovascular related adverse events compared with allopurinol.
Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Myocardial Infarction
PubMed: 34013998
DOI: 10.1002/clc.23643