INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. METHODS: This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. RESULTS: The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 ( P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant. CONCLUSIONS: IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. TRIAL REGISTRATION https://classic.clinicaltrials.gov/ , NCT01548001.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Chromones/adverse effects* ; Double-Blind Method ; Drug Therapy, Combination ; Methotrexate/adverse effects* ; Treatment Outcome ; Sulfonamides

INTRODUCTION: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically. METHODS: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups. RESULTS: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups ( P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life. CONCLUSIONS RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients.
Humans ; Arthritis, Rheumatoid/diagnosis* ; Male ; Female ; Middle Aged ; Rheumatoid Factor/blood* ; Anti-Citrullinated Protein Antibodies/blood* ; Adult ; Quality of Life ; Prospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Peptides, Cyclic/immunology* ; Prednisolone/therapeutic use* ; Surveys and Questionnaires ; Severity of Illness Index ; Prognosis

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Humans ; Arthritis, Psoriatic/drug therapy* ; Interleukin-17 ; Interleukin Inhibitors ; Antirheumatic Agents/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Interleukin-23/therapeutic use*

BACKGROUND

Post-ERCP pancreatitis (PEP) remains the most common complication following endoscopic retrograde cholangiopancreatography (ERCP). Rectal indomethacin is one of the recommended medications given to prevent pancreatitis in high-risk patients undergoing ERCP.

This study aims to evaluate the effectiveness of diclofenac in preventing PEP, to compare its different routes of administration, and to determine the severity of pancreatitis in patients who develop PEP.

Databases from PubMed, ScienceDirect and COCHRANE Library were searched for randomized controlled trials (RCTs) comparing diclofenac with placebo in the prevention of PEPup to August 2020. Risk ratio at 95% Confidence Intervals (CI) were calculated to evaluate the incidence of the interested outcomes.

Eleven RCTs with a total population of 2,012 were reviewed in this study. Diclofenac was associated with a significant reduction in overall risk of PEP compared with patients with placebo (RR = 0.59; 95%, 0.47 0.74; P < 0.000001), with a mild heterogeneity (P = 0.05; I2 = 41%). Subgroup analyses showed that rectal diclofenac was the superior choice to significantly reduce the overall incidence of PEP(RR = 0.34; 95%, 0.23-0.51; P < 0.000001).

Rectal diclofenac significantly reduces the risk of PEPand therefore, should be recommended as routine for clinical use in adult patients who will undergo ERCP.

OBJECTIVE: To investigate the current status of methotrexate (MTX) application in rheumatoid arthritis (RA) patients. METHODS: The clinical and laboratory data of RA patients who attended in the Department of Rheumatology and Immunology of Peking University Third Hospital from January 1, 2022 to November 31, 2023 were collected retrospectively. In order to figure out the relationship between MTX use and RA disease control, we recorded information including the starting dose, maximum dose, current dose, reasons of discontinuation of MTX, etc. The t test, Mann-Whitney U test, Chi-square test, Fisher' s exact probability and multivariable Logistic regression were used for analysis. RESULTS: A total of 239 RA patients were enrolled, including 201 females and 38 males with a mean age of (54.5±14.3) years. Among them, 101 patients reached the therapeutic target [clinical remission or low disease activity assessed by 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR)], accounting for 42.2% of the RA patients. Twenty-six patients met the European League Against Rheumatism (EULAR) definition of difficult-to-treat (D2T) RA, accounting for 10.9% of RA patients. The proportion of the RA patients who had ever used MTX was 84. 1%, and those who were currently on it accounted for only 39.7%. The MTX dose was generally low, with a starting dose of (9.5±3.0) mg/week, the maximum dose of 15.0 (10.0, 15.0) mg/week, and the current dose being (12.4±2.7) mg/week. The most common reasons for MTX dose reduction or discontinuation were adverse reactions, mainly including abnormalities of hepatic function, gastrointestinal discomfort, leucopenia, etc. Those who were currently on MTX had a higher rate of treatment to target (52.6% vs. 35.4%, P>0.05), lower disease activity score (DAS28-ESR, 3.6±1.8 vs. 4.2±1.8, P < 0.05), and fewer tender joint counts (4.8±8.3 vs. 8.6±10.4, P < 0.05) as compared with those who were not taking the drug, while swollen joint count, pain visual analog score and patient' s global score, C-reactive protein (CRP) level and ESR level were not significantly different between the two groups. Compared with those who did not reach the target of treatment, those who did had a higher rate of current MTX application (48.5% vs. 33.3%, P < 0.05), but the history of MTX did not differ between the two groups (84.2% vs. 84.1%, P>0.05). The maximum dose of MTX (median 15.0 mg/week vs. 13.7 mg/week, P>0.05) and the current dose [(12.9±2.5) mg/week vs. (11.8±2.8) mg/week, P>0.05] was higher in those who achieved the target, while the starting dose [(9.6±2.8) mg/week vs. (9.5±3.1) mg/week, P>0.05] and the rate of prior MTX (84.2% vs. 83.3%, P>0.05) was comparable between the two groups. The D2T RA patients had a higher rate of previous MTX use (96.2% vs. 82.6%, P < 0.05) and a higher starting dose [(11.6±4.3) mg/week vs. (9.8±2.7) mg/week, P>0.05], while the maximum dose (median 12.5 mg/week vs. 15.0 mg/week, P>0.05) and the current dose were both lower [(11.6±3.2) mg/week vs. (12.5±2.6) mg/week, P>0.05] than the non-D2T RA patients. CONCLUSION The proportion of regular use of MTX among RA patients was low and the dose was generally small. The RA patients with regular use of MTX had a higher rate of achieving treatment target and lower disease activity. Those who achieved the target had a higher rate of current MTX use, higher maximum and current doses than those who did not. The D2T RA patients had lower maximum and current doses of MTX than the non-D2T RA patients. Therefore, increasing the usage and dosage of MTX in RA patients may help to improve the rate of achieving treatment targets.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/therapeutic use* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Adult ; Blood Sedimentation ; Severity of Illness Index ; Remission Induction

Rheumatoid arthritis (RA) and myasthenia gravis (MG) are two distinct autoimmune diseases. Compared with the general population, the incidence of RA is notably higher among patients with MG. Similarly, the rate of MG in patients diagnosed with RA is also significantly increased. In this report, we presented an elderly female patient with a history usage of long-term glucocorticoid and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), whose RA symptoms remained inadequately controlled. She later exhibited drooping of the right eyelid and double vision, leading to a diagnosis of ocular myasthenia gravis (OMG). Then, we made a literature review and found that the RA patients with co-existing MG were relatively more common in middle-aged and elderly women, and most of them did not have thymoma. Thymoma wasn ' t found in our patient, which was consistent with the cli-nical characteristics of RA complicated with MG reported in previous reports. In addition, there was li-mited treatment experience in patients with both RA and MG. The treatment stratergies for RA or MG included glucocorticoids and immunosuppressants. Among the 18 patients we analyzed, 8 patients expe-rienced relief after csDMARDs, while other 8 patients received biologics or targeted DMARDs, including tumor necrosis factor inhibitors (TNFi) in 5 cases, JAK inhibitors in 2 cases, and B-cell depletion therapy (rituximab) in 2 cases. What called for special attention was that one RA patient was diagnosed with MG after using 23 months of methotrexate and 6 weeks of etanercept (TNFi), with rituximab 1 000 mg for the first time, followed by 500 mg every 6 months, and finally both RA and MG were well controlled. For the patient in this study, MG symptoms improved with increased dosage of prednisone. In order to tapper the dose of glucocorticoid, it was necessary for more potent immunosuppressant for both RA and MG. Given her history of cardiac conditions, JAK inhibitors were not considered, and due to the uncertain efficacy of TNFi, we chose to administer low-dose rituximab (100 mg). Subsequent follow-up revealed stable conditions for both RA and MG, allowing for discontinuance of glucocorticoid after 5 months. It reflected the potential efficacy and cost-effectiveness of low-dose, long-interval rituximab in treating RA patients combined with MG, while it also minimized infection risks. However, the duration for subsequent infusions remained uncertain and required further observation. In conclusion, RA combined with MG is rare. For patients exhibiting poor responses to csDMARDs, low-dose, long-interval rituximab might be a promising treatment option.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Rituximab/administration & dosage* ; Myasthenia Gravis/drug therapy* ; Female ; Antirheumatic Agents/administration & dosage* ; Aged ; Glucocorticoids/therapeutic use*

This article comprehensively reviews the research progress in the management principles of acute closed soft tissue injuries,summarizing the retention and updates of the four main principles (RICE,PRICE,POLICE,and PEACE&LOVE) at different stages.Traditional methods such as compression,elevation,rest,and protection remain valuable.However,with the advancement in rehabilitation philosophy,early active rehabilitation plays an increasingly important role in the tissue healing process.Traditional cold therapy remains a choice because of its benefits.Non-steroidal anti-inflammatory drugs play a positive role in relieving the acute pain and swelling and improving the function of soft tissue,being preferred by both patients and medical practitioners.Therefore,advantages outweigh disadvantages in the clinical application of non-steroidal anti-inflammatory drugs.Finally,modern medical models have begun to incorporate more social and psychological factors,focusing on patients' mental state and social environment,while guiding patients to actively participate in the rehabilitation process,which can accelerate the recovery process and improve treatment outcomes.
Humans ; Soft Tissue Injuries/therapy* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use*

Humans ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects* ; Aspirin/therapeutic use* ; Respiration Disorders ; Respiratory Tract Diseases