Risk for infections with glucocorticoids and DMARDs in patients with rheumatoid arthritis

Riley, Thomas; George, Michael

doi:10.1136/rmdopen-2020-001235

Cited by 30 publications

(24 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Patients with RA are known to be at risk for developing HZ, including ophthalmic HZ and post-herpetic neuralgia [ 117 ]. Clinical experience has shown that this baseline risk is enhanced by drugs such as JAK inhibitors (mostly tofacitinib), TNFis, and IL-6Ris (mostly infliximab), especially when used in combination with GCs or in patients with co-morbidities or 50 years of age or older [ 118 ]. The mechanisms underlying the increased risk of VZV reactivation in these patients are unclear, but a possible explanation is that the drugs interfere with the onset and persistence of VZV-specific memory T-cells [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In a US nationwide analysis, infection was the most common complication of spine surgery (18) and was the leading cause of readmission after cervical fusion surgery in patients with RA (43). Among DMARDs, biologics, JAK inhibitors and high doses of glucocorticoids have been associated with an increased risk of infections (44,45). However, con icting results of biological DMARDs, mainly tumour necrosis factor antagonists, have been reported in many studies, including both increased and unchanged risks of superimposed infections after surgery (46).…”

Section: Discussionmentioning

confidence: 99%

Risk Factor Analysis of Perioperative Complications in Patients with Rheumatoid Arthritis Undergoing Primary Cervical Spine Surgery

Sakuraba

Omori

Kai

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Rheumatoid arthritis (RA) often causes cervical spine lesions as the disease condition progresses, which induce occipital neuralgia or cervical myelopathy requiring surgical interventions. Meanwhile, patients with RA are susceptible to infection or other complications in the perioperative period because they frequently have comorbidities and use immunosuppressive medications. However, the risk factors or characteristics of patients with RA who experience perioperative complications after cervical spine surgery remain unknown. A risk factor analysis of perioperative complications in patients with RA who underwent primary cervical spine surgery was conducted in the present study.Methods: A total of 139 patients with RA who underwent primary cervical spine surgery from January 2001 to March 2020 were retrospectively investigated. Age and height, weight, serum albumin, serum C-reactive protein, American Society of Anesthesiologists Physical Status (ASA-PS), Charlson comorbidity index, medications used, cervical spine lesion, surgery time, bleeding volume, and procedures were collected from medical records to compare the patients with complications to those without complications after surgery. The risk factors for perioperative complications were assessed by univariate and multivariate logistic regression analysis.Results: Twenty-eight patients (20.1%) had perioperative complications. Perioperative complications were significantly associated with the following factors [data presented as odds ratio (confidence interval)]: lower height [0.928 (0.880-0.980), p=0.007], higher ASA-PS [2.296 (1.007-5.235), p=0.048], longer operation time [1.013 (1.004-1.021), p=0.003], more bleeding volume [1.004 (1.000-1.007), p=0.04], higher rates of vertical subluxation [2.914 (1.229-6.911), p=0.015] and subaxial subluxation (SAS) [2.507 (1.063-5.913), p=0.036], occipito-cervical (OC) fusion [3.438 (1.189-9.934), p=0.023], and occipito-cervical/thoracic (long) fusion [8.021 (2.145-29.99), p=0.002] in univariate analyses. In multivariate analyses, lower height [0.915 (0.860-0.974), p=0.005], higher ASA-PS [2.622 (1.023-6.717), p=0.045] and long fusion [7.289 (1.694-31.36), p=0.008] remained risk factors. High-dose prednisolone use [1.247 (1.024-1.519), p=0.028], SAS [6.413 (1.381-29.79), p=0.018], OC fusion [17.93 (1.242-258.8), p=0.034] and long fusion [108.1 (6.876-1699), p<0.001] were associated with severe complications.Conclusions: ASA-PS and long fusion could be indicators predicting perioperative complications in patients with RA after cervical spine surgery. In addition, cervical spine lesions requiring OC fusion or long fusion and high-dose prednisolone use were suggested to be risk factors for increasing severe complications.

show abstract

“…The formation of the thiourea was confirmed with the appearance of a clear downfield signal for the (C=S) in the carbon NMR spectra at around 181 ppm. Moreover, the methylene (-CH2-) bridge available in compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) was observed in the proton NMR spectra as two protons appearing in the range of 4.37-4.95 ppm. We decided to explore the effect of diverse benzyl substitutions on the NF-κB and EGFR inhibitory activity.…”

Section: Chemistrymentioning

confidence: 99%

“…The commonly prescribed anti-inflammatory drugs have potentially serious side effects: NSAIDs are known for their potential to induce gastrointestinal ulceration and bleeding [ 5 ]. Many antirheumatic drugs, such as methotrexate, sulfasalazine, and hydroxychloroquine, may cause an increased risk of infection and hepatotoxicity [ 6 , 7 ]. Anti-inflammatory glucocorticoids are effective, but the therapy has metabolic and cardiovascular side effects, and long-term treatment is limited due to the development of resistance [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Development of (4-Phenylamino)quinazoline Alkylthiourea Derivatives as Novel NF-κB Inhibitors

et al. 2022

View full text Add to dashboard Cite

For many inflammatory diseases, new effective drugs with fewer side effects are needed. While it appears promising to target the activation of the central pro-inflammatory transcription factor NF-κB, many previously discovered agents suffered from cytotoxicity. In this study, new alkylthiourea quinazoline derivatives were developed that selectively inhibit the activation of NF-κB in macrophage-like THP−1 cells while showing low general cytotoxicity. One of the best compounds, 19, strongly inhibited the production of IL-6 (IC50 = 0.84 µM) and, less potently, of TNFα (IC50 = 4.0 µM); in comparison, the reference compound, caffeic acid phenethyl ester (CAPE), showed IC50s of 1.1 and 11.4 µM, respectively. Interestingly, 19 was found to block the translocation of the NF-κB dimer to the nucleus, although its release from the IκB complex was unaffected. Furthermore, 19 suppressed the phosphorylation of NF-κB-p65 at Ser468 but not at Ser536; however, 19 did not inhibit any kinase involved in NF-κB activation. The only partial suppression of p65 phosphorylation might be associated with fewer side effects. Since several compounds selectively induced cell death in activated macrophage-like THP−1 cells, they might be particularly effective in various inflammatory diseases that are exacerbated by excess activated macrophages, such as arteriosclerosis and autoimmune diseases.

show abstract

Risk for infections with glucocorticoids and DMARDs in patients with rheumatoid arthritis

Cited by 30 publications

References 48 publications

Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review

Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review

Risk Factor Analysis of Perioperative Complications in Patients with Rheumatoid Arthritis Undergoing Primary Cervical Spine Surgery

Development of (4-Phenylamino)quinazoline Alkylthiourea Derivatives as Novel NF-κB Inhibitors

Contact Info

Product

Resources

About