Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized. We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency. A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993. Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment. This was begun as a single oral dose of 5mg/week. After 2 doses, the patient was admitted to the hospital with general weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal, but the serum albumin level was 2.7 g/dl. The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and intravenous prophylactic antibiotic therapy were required. Her condition was improved. In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency. Close monitoring of associated risk factors, particularly impaired renal function, should be mandatory for all patients who are receiving MTX therapy.
Aged ; Antirheumatic Agents/adverse effects* ; Antirheumatic Agents/administration & dosage ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/complications ; Case Report ; Female ; Human ; Kidney Failure, Chronic/complications ; Methotrexate/adverse effects* ; Methotrexate/administration & dosage ; Pancytopenia/chemically induced* ; Risk Factors

English articles on abatacept, golimumab, and tocilizumab in rheumatoid arthritis published between 2002 and 2009 were reviewed systematically. All randomized clinical trials, open-label extensions, meta-analyses, and reviews were examined. There were thirteen articles on abatacept, four on golimumab, and seven on tocilizumab. All three drugs were effective in methotrexate-naive, methotrexate-incomplete responders, and tumor-necrosis-factor-failure rheumatoid arthritis patients. Of the three, only abatacept has been tested in a head-to-head trial with infliximab, in which it was found to be equivalent to infliximab. Golimumab resulted in a more modest improvement than the others in methotrexate-naive patients, although no direct comparisons among the three drugs were possible or appropriate. Descriptive analysis of adverse events showed that patients receiving abatacept, golimumab, and tocilizumab were subject to more adverse events than controls overall, as expected. In the abatacept studies, a few cases of tuberculosis, more cardiovascular events and gastrointestinal bleedings and more basal cell carcinoma were seen. Golimumab was associated with more skin rashes and pneumonia, while tocilizumab was associated with increased lipids, more liver-function abnormalities, and neutropenia. These new medications are useful additions to the rheumatologic armamentarium and represent greater convenience (golimumab) or different mechanisms of action (abatacept and tocilizumab) than tumor-necrosis-factor inhibitors for treating rheumatoid arthritis. As expected, some adverse events occur when using these drugs and patients need to be watched carefully.
Antibodies, Monoclonal/*administration & dosage/adverse effects ; Antirheumatic Agents/*administration & dosage/adverse effects ; Arthritis, Rheumatoid/*drug therapy ; Biological Therapy ; Humans ; Immunoconjugates/*administration & dosage/adverse effects

OBJECTIVETo observe the clinical efficacy and safety of Corydalis composite (CDC) combined with methotrexate (MTX) in treating rheumatoid arthritis (RA).

METHODSSeventy-six RA patients were randomly assigned to 2 groups, 37 in the treated group received the combined therapy, and the 39 received MTX treatment alone, all were treated for 12 weeks. Efficacy of treatment was evaluated adopting the standard of American College of Rheumatology (ACR), taking ACR20 as the chief criterion; ACR50, ACR70 as well as the clinical indexes and items in Health Account Questionnaire (HAQ) as the auxiliary criteria, including joint swelling index, joint tenderness index, holding power, morning stiffness time, resting pain, erythrocyte sedimentation rate (ESR), C-reactive protein. And the adverse reaction was recorded at the same time.

RESULTSAfter being treated for 4, 8 and 12 weeks, the ACR20 response rate reached 35.14%, 59.46% and 70.27% respectively in patients of the treated group, while that in the control group was 17.95%, 35.90% and 46.15% respectively, significant difference between groups was shown in the outcome of week 8 and 12 (P < 0.05). ACR50 and ACR70 improving rate at all the time points of observation were increased in the treated group, with the ACR50 improving rate at week 12 higher than that in the control group (43.24% vs. 20.51%, P < 0.05). As compared with the control group, the improvements in all the auxiliary criteria were more significant in the treated group (P < 0.05). The incidence of adverse reaction was less in the treated group than in the control group (32.43% vs. 56.41%, P < 0.05), particularly in term of the damage on liver (0 vs. 10.26%, P < 0.05).

CONCLUSIONCDC combined with MTX is more effective than MTX alone in treating active RA with less adverse reaction.

Adult ; Antirheumatic Agents ; administration & dosage ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Biological Products ; therapeutic use ; Corydalis ; Drug Therapy, Combination ; Female ; Humans ; Male ; Methotrexate ; administration & dosage ; therapeutic use ; Middle Aged ; Treatment Outcome

BACKGROUND: This review evaluated the safety and efficacy of etanercept in patients with ankylosing spondylitis (AS). METHODS: Of 59 patients with AS, this study reviewed 11 patients who were refractory to conventional therapy and treated with etanercept from September 2005 to January 2008. The mean follow-up duration was 13.6 months. The general improvement was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and adverse effects, complications and inflammatory markers were also assessed. RESULTS: The mean BASDAI decreased from 7.1 +/- 1.6 before treatment to 4.2 +/- 1.8 at 3 months after the etanercept treatment (p = 0.001). The mean erythrocyte sedimentation rate and C-reactive protein were decreased significantly by the etanercept treatment. The greatest improvement in symptoms was enthesitis, followed by skin involvement and morning stiffness. There was a significant difference in the improvement in BASDAI along with the follow up duration (p = 0.04). A serious infection was observed as a complication in 1 case. CONCLUSIONS: These results suggest that etanercept can induce significant improvement in most patients with less damage. A trial of tumor necrosis factor inhibition is indicated in all AS patients who do not achieve adequate disease control with disease-modifying antirheumatic drugs, such as methotrexate, leflunomide etc. The patients treated with etanercept should be educated about the possibility of infection and monitored closely.
Adult ; Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/adverse effects ; Antirheumatic Agents/*administration & dosage/adverse effects ; Blood Sedimentation ; C-Reactive Protein/analysis ; Drug Administration Schedule ; Female ; Humans ; Immunoglobulin G/*administration & dosage/adverse effects ; Injections, Subcutaneous ; Male ; Middle Aged ; Receptors, Tumor Necrosis Factor/*administration & dosage ; Spondylitis, Ankylosing/diagnosis/*drug therapy ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors ; Young Adult

Alopecia ; chemically induced ; diagnosis ; Antirheumatic Agents ; administration & dosage ; adverse effects ; Arthritis, Rheumatoid ; drug therapy ; Biopsy ; methods ; Cyclosporine ; administration & dosage ; Dermatologic Agents ; administration & dosage ; Drug Hypersensitivity Syndrome ; diagnosis ; etiology ; physiopathology ; therapy ; Humans ; Male ; Middle Aged ; Prednisolone ; administration & dosage ; Skin ; pathology ; Sulfasalazine ; administration & dosage ; adverse effects ; Symptom Flare Up ; Treatment Outcome ; Vitiligo ; chemically induced ; diagnosis

Antirheumatic Agents ; administration & dosage ; therapeutic use ; Biological Products ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Evidence-Based Medicine ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lupus Erythematosus, Systemic ; drug therapy ; pathology ; Lupus Nephritis ; drug therapy ; pathology ; Severity of Illness Index

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate, a synthetic disease-modifying antirheumatic drug (DMARD), and biologic DMARD has revolutionized treatment of RA. Clinical remission is now realistic targets, achieved by a large proportion of RA patients, and rapid and appropriate induction of remission by intensive treatment with biological DMARD and methotrexate is prerequisite to halt joint damage and functional disabilities. However, biological DMARD is limited to intravenous or subcutaneous uses and orally available small but strong molecules have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active patients with methotrexatenaive, inadequately responsive to methotrexate or tumor necrosis factor (TNF)-inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. Meanwhile, association of tofacitinib on carcinogenicity and malignancy is under debate and further investigation on post-marketing survey would be warranted. On the other hand, discontinuation of a biological DMARD without disease flare is our next goal and desirable from the standpoint of risk reduction and cost effectiveness, especially for patients with clinical remission. Recent reports indicate that more than half of early RA patients could discontinue TNF-targeted biological DMARD without clinical flare and functional impairment after obtaining clinical remission. Contrarily, for established RA, fewer patients sustained remission after the discontinuation of biological DMARD and "deep remission" at the discontinuation was a key factor to keep the treatment holiday of biological DMARD.
Administration, Oral ; Antirheumatic Agents/*administration & dosage/adverse effects ; Arthritis, Rheumatoid/diagnosis/*drug therapy/metabolism/physiopathology ; Biological Products/administration & dosage ; Disability Evaluation ; Drug Administration Schedule ; Humans ; Janus Kinases/antagonists & inhibitors/metabolism ; Molecular Targeted Therapy ; Predictive Value of Tests ; Protein Kinase Inhibitors/administration & dosage ; Recovery of Function ; Remission Induction ; Signal Transduction/drug effects ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors/metabolism

The ongoing pandemic in Singapore is part of a global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To control the spread of COVID-19 and prevent the healthcare system from being overwhelmed, 'circuit breaker' measures were introduced between 7 April and 1 June 2020 in Singapore. There is thus a crucial need for innovative approaches to the provision and delivery of healthcare in the context of safe-distancing by harnessing telemedicine, especially for patients with chronic diseases who have traditionally been managed in tertiary institutions. We present a summary of how the Virtual Monitoring Clinic has benefited the practice of our outpatient rheumatology service during the COVID-19 pandemic. The virtual consultations address the need for safe-distancing by limiting face-to-face appointments and unnecessary exposure of patients to the hospital where feasible. This approach ensures that the patients are monitored appropriately for drug toxicities and side-effects, maintained on good disease control, and provided with patient education.
Ambulatory Care/methods* ; Antirheumatic Agents/therapeutic use* ; COVID-19 ; Delivery of Health Care ; Humans ; Nurse Practitioners ; Pharmacists ; Rheumatic Diseases/drug therapy* ; Rheumatology/methods* ; SARS-CoV-2 ; Singapore ; Telemedicine/organization & administration* ; Tertiary Care Centers

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
Animals ; Antirheumatic Agents ; administration & dosage ; Arthritis ; chemically induced ; drug therapy ; urine ; Biomarkers ; urine ; Collagen Type II ; Dose-Response Relationship, Drug ; Immunosuppressive Agents ; administration & dosage ; Magnetic Resonance Spectroscopy ; methods ; Male ; Metabolome ; Methotrexate ; administration & dosage ; Proteome ; analysis ; Protons ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Treatment Outcome

BACKGROUND/AIMS: The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA). METHODS: A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches. RESULTS: Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. CONCLUSIONS: Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile.
Antirheumatic Agents/administration & dosage/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Humans ; Janus Kinases/antagonists & inhibitors ; Methotrexate/therapeutic use ; Piperidines/administration & dosage/adverse effects/*therapeutic use ; Protein Kinase Inhibitors/administration & dosage/adverse effects/therapeutic use ; Pyrimidines/administration & dosage/adverse effects/*therapeutic use ; Pyrroles/administration & dosage/adverse effects/*therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome