BACKGROUND: Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. RESULTS: In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003). CONCLUSION This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
Antirheumatic Agents/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Humans ; Network Meta-Analysis ; Pharmaceutical Preparations ; Randomized Controlled Trials as Topic ; Tuberculosis/drug therapy*

To systemically evaluate the efficacy and safety of sinomenine combined with methotrexate(SIN+MTX) in the treatment of rheumatoid arthritis(RA). Literature databases of Wanfang, CNKI, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were retrieved comprehensively for relevant clinical trials. The literature retrieval time was from database establishment to February 4, 2020. The quality of literatures was assessed by the Cochrane Evaluation Handbook 5.1.0, and qualified literature was reviewed and analyzed by using the RevMan 5.3 statistical software. Twenty randomized controlled trials met the inclusion criteria, and were enrolled in the Meta-analysis. The results showed that SIN+MTX remarkably reduced DAS28(MD=-0.85, 95%CI[-1.03,-0.67], P<0.000 01), and improved total efficiency(P<0.000 01). SIN+MTX could inhibit swollen joint count(MD=-1.19, 95%CI[-1.75,-0.63], P<0.000 1), tender joint count(MD=-1.58, 95%CI[-2.89,-0.28], P=0.02) and reduce morning stiffness time(MD=-8.44, 95%CI[-11.82,-5.07], P<0.000 01) compared with control group. The results showed that SIN+MTX was equal to control group in grip strength(SMD=0.20,95%CI[-1.11,1.51],P=0.77). SIN+MTX remarkably alleviated the erythrocyte sedimentation rate(MD=-9.87, 95%CI[-14.52,-5.22], P<0.000 1), C-reactive protein(SMD=-0.30, 95%CI[-0.51,-0.09], P=0.005), and rheumatoid factor(MD=-11.23,95%CI[-13.81,-8.65],P<0.000 01). The frequency of adverse reactions were reduced compared with that in the control group(P<0.000 01). Current clinical studies demonstrate that the efficacy and safety of SIN+MTX in the treatment of RA were superior to control group. However, due to the low quality and quantity of the included studies, high-quality randomized controlled trials are necessary to support the clinical evidences.
Antirheumatic Agents/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Methotrexate/adverse effects* ; Morphinans

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 ; adverse effects ; Dermatitis, Exfoliative ; Humans ; Hydroxychloroquine ; adverse effects ; Lupus Erythematosus, Systemic ; drug therapy ; Psoriasis ; chemically induced

Rheumatoid arthritis (RA) is expected to increase in Africa and South Africa. Due to the low numbers of rheumatologists in South Africa, specialist physicians also have to care for patients with RA. Furthermore several new developments have taken place in recent years which improved the management and outcome of RA. Classification criteria were updated, assessment follow-up tools were refined and above all, several new biological disease-modifying anti-rheumatic drugs were developed. Therefore it is imperative for specialist physicians to update themselves with the newest developments in the management of RA. This article provides an overview of the newest developments in the management of RA in the South African context. This approach may well apply to countries with similar specialist to patient ratios and disease profiles.
Antirheumatic Agents/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/diagnosis/*drug therapy/epidemiology ; Diffusion of Innovation ; Humans ; Practice Guidelines as Topic ; Practice Patterns, Physicians' ; Prevalence ; *Rheumatologists/standards ; Risk Factors ; Severity of Illness Index ; South Africa/epidemiology ; *Specialization ; Treatment Outcome

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

Controlled clinical trials of integrative therapies available to patients with rheumatoid arthritis (RA) improved dramatically in the past 20 years, largely because of the growing need and the methodologies improvement. Tripterygium wilfordii Hook. F., a typical example of popular use herb, has been extensively studied in trials. However, clear and convincing evidence of integrative therapy, effectiveness and safety, remains insufficient to make decision. Many research efforts are hampered by standing problems with 'syndrome' recruitment failure. In addition, the outcome multiplicity induces the findings inefficiency to generalize to RA patients at large. Development of validated syndrome outcomes and methodologies has also been critical. Current efforts to enhance the understanding of integrative treatment options for patients with RA include the development of drug-specific rather than disease-specific strategies, studies in predictive biomarkers, and development of peer-review trial protocol for regular clinical trials.
Antirheumatic Agents ; adverse effects ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Clinical Trials as Topic ; Humans ; Integrative Medicine ; Tripterygium ; chemistry

Adalimumab ; adverse effects ; therapeutic use ; Antirheumatic Agents ; adverse effects ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; immunology ; Asian Continental Ancestry Group ; Autoantibodies ; immunology ; Female ; Humans ; Immunoglobulin A ; immunology ; Middle Aged ; Nephritis ; etiology ; immunology

BACKGROUND/AIMS: To evaluate the impact on mortality of anti-tumor necrosis factor (anti-TNF) treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We retrospectively reviewed the medical records of 100 RA-ILD patients who visited our tertiary care medical center between 2004 and 2011, identified those treated with an anti-TNF agent, divided patients into non-survivor and survivor groups and evaluated their clinical characteristics and causes of death. RESULTS: A total of 24 RA-ILD patients received anti-TNF therapy, of whom six died (25%). Mean age at initiation of anti-TNF therapy was significantly higher in the nonsurvivor versus survivor group (76 years [range, 66 to 85] vs. 64 years [range, 50 to 81], respectively; p = 0.043). The mean duration of anti-TNF treatment in the non-survivor group was shorter (7 months [range, 2 to 14] vs. 23 months [range, 2 to 58], respectively; p = 0.030). The duration of anti-TNF therapy in all nonsurviving patients was < 12 months. Pulmonary function test results at ILD diagnosis, and cumulative doses of disease-modifying drugs and steroids, did not differ between groups. Five of the six deaths (83%) were related to lung disease, including two diffuse alveolar hemorrhages, two cases of acute exacerbation of ILD, and one of pneumonia. The sixth patient died of septic shock following septic arthritis of the knee. CONCLUSIONS: Lung complications can occur within months of initial anti-TNF treatment in older RA-ILD patients; therefore, anti-TNF therapy should be used with caution in these patients.
Adult ; Aged ; Aged, 80 and over ; Antirheumatic Agents/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/complications/diagnosis/*drug therapy/immunology/mortality ; Female ; Humans ; Lung Diseases, Interstitial/diagnosis/etiology/*mortality ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Tertiary Care Centers ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFalpha) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFalpha inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFalpha therapy in patients with TNFalpha-associated TB. We used data of 1,012 patients with RA or AS treated with TNFalpha inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-gamma releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFalpha therapy. All patients discontinued TNFalpha inhibitors with starting the treatment of TB. Eight patients were re-administered TNFalpha inhibitors due to disease flares and promptly improved without recurrence of TB. TNFalpha inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Antirheumatic Agents/adverse effects/therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Enzyme Inhibitors/adverse effects/therapeutic use ; Female ; Humans ; Hydroxychloroquine/adverse effects/therapeutic use ; Immunoglobulin G/adverse effects/therapeutic use ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Interferon-gamma Release Tests ; Male ; Methotrexate/adverse effects/therapeutic use ; Middle Aged ; Mycobacterium tuberculosis/isolation & purification ; Receptors, Tumor Necrosis Factor/therapeutic use ; Retrospective Studies ; Spondylitis, Ankylosing/*drug therapy ; Tuberculin Test ; Tuberculosis/*chemically induced/microbiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors