Precautions before starting tofacitinib in persons with rheumatoid arthritis

Tofacitinib is an immunosuppressive and disease-modifying therapy in rheumatoid arthritis. It may result in many infections flaring up. It is important to take precautions of all kinds (cardiovascular, malignancy, infections etc.) before starting tofacitinib. In this article, we have highlighted important steps where we need to take precautions before starting tofacitinib.     

Gold complex research in medical science. Difficulties with experimental design

Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been established. Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium thiomalate thus can exist in several different physical states which may have different biological activity. In addition the pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action, efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist at different pH. Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow or a colourless solution. These have some similar but several different biological activities. Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to the wide variation in physical structure and biological activities exhibited by these compounds.     

One-year clinical results with actarit—a preliminary report

Abstract

The effectiveness and safety of 1-year treatment with actarit were evaluated in patients with rheumatoid arthritis. Treatment was continued for 1 year or longer in 18 of the 34 patients. Early improvement in morning stiffness, grip strength, joint score and the Lansbury’s index were observed. Improvement in 1-h eythrocyte sedimentation rate was observed at the 12-month assessment. IgG was decreased at the 12-month assessment. Obvious improvement in C-reactive protein was not seen through the trial. No abnormal findings were noted in routine blood tests. Adverse reactions of special note were skin eruption in one patient and digestive symptom in one patient. However, no serious adverse reactions were observed.     

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study

We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.     

Gastrointestinal symptoms associated with enteric-coated sulfasalazine (Azulfidine EN tablets)

 To investigate both the incidence and the dosage used to treat gastrointestinal (GI) symptoms associated with enteric-coated sulfasalazine (Azulfidine EN, AZL) in patients with rheumatoid arthritis (RA), we studied the clinical history of 153 RA patients, and any available data on GI symptoms that might have been associated with AZL. GI symptoms appeared in 64 (42.5%) of the 153 cases. There were 19 events of nausea, vomiting, or dyspepsia, 14 events each of epigastric discomfort and reduction or loss of appetite, 10 events of epigastric, stomach, or abdominal pain, 9 events of heartburn, 8 events of mouth ulcer, 3 events each of loss of taste and abdominal bloating or borborygmus, 2 events each of diarrhea or loose stools, hematemesis or melanemia, and gastric or esophageal ulcer, and 1 event of stomatitis. These results indicate that GI symptoms associated with AZL are usually mild and treatment can continue, with almost all cases responding to a reduction in dose or drug cessation. In some cases, a histamine receptor-2 blocker or proton pump inhibitor is also required. Received: October 11, 2001 / Accepted: March 29, 2002 Correspondence to: S. Okubo     

Have traditional DMARDs had their day?

This review tries to answer the question of whether in the face of the recently introduced biologics conventional disease-modifying antirheumatic drugs (DMARDs) can still be recommended in the treatment of rheumatoid arthritis (RA). We start with an overview of the oldest conventional DMARD, injectable gold (Au), which was introduced in the treatment of RA in the 1920s. The effect of gold is directed at a number of different sites of the immune system. A significant improvement of clinical and biochemical disease activity parameters as well as an inhibition of X-ray progression has been shown in many studies. Head-to-head comparisons between gold and high-dose methotrexate (MTX) demonstrated no significant difference but some advantages for gold. Since trials comparing biologics with gold will never be performed, an indirect comparison was done by analyzing the results of trials with gold with those with biologics. Conclusions from such comparisons have to be drawn with caution especially since the methodology for performing trials has changed with time. We selected four trials with gold (two open, one placebo-controlled, and one comparison with MTX) and five trials with biologics (three placebo-controlled, one dose escalation study, and one comparison with MTX). In all these trials baseline data regarding swollen joint count (SJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were roughly comparable and, with the exception of interleukin (IL)-1 RA, demonstrated a similar improvement of over 50% already after 6 months [with faster onset with tumor necrosis factor (TNF)-alpha blockade]. American College of Rheumatology (ACR) response data were not available for the older gold trials. European League Against Rheumatism (EULAR) response criteria could be calculated for the Au/MTX trial and were—for these compounds—only slightly inferior to the results with adalimumab. X-ray response is especially difficult to compare across studies. Although an inhibition with Au and MTX could be demonstrated, this occurred—similar to corticosteroid treatment—earlier and more pronounced with TNF-alpha blockers. We confirm the statement of Weinblatt that the most modern DMARDs do not appear to be much better than the oldest one indicating that conventional DMARDs are not outdated. Therefore, a sufficient trial of conventional DMARDs should precede the introduction of treatment with the very expensive biologics.     

Important determinants of the patient choice between TNF- vs. non-TNF Biologic disease-modifying anti-rheumatic drugs (DMARDs) for active rheumatoid arthritis (RA)

ObjectiveTo assess why patients choose TNF- versus non-TNF biologics for treating active rheumatoid arthritis (RA) after methotrexate-failure.MethodsParticipants responded to the question “What sort of things help a patient decide the treatment choice between the two types of injectable biologics, TNF biologic versus non-TNF biologic, for treating active rheumatoid arthritis when methotrexate fails to control RA disease activity?” They nominated responses, discussed and then voted.ResultsForty-four patients participated in 10 nominal groups (Birmingham; n = 6; New York City: n = 4), who were predominantly female (86%), 68% white, with a mean age of 65 (standard deviation [SD], 12) years. Present/past DMARDs included methotrexate in 91%, glucocorticoids in 11%, and biologics and/or Jak-inhibitors in 68% of participants. Pain and fatigue were mild-moderate with means of 3.9 (SD, 2.5) and 4.3 (SD, 2.5), respectively, on 0-10 scale; mean morning joint stiffness was 1.3 hours (SD, 2.1). The number of groups that nominated each response and total votes were as follows: (1) Side effects/fear of side effects: 10/10; 31% votes (82/264); (2) Efficacy/ability to reduce joint damage: 9/10; 30% votes (80/264); (3) Doctor's opinion, 6/10; 12% votes (32/264); (4) Cost, 7/10; 9% votes (25/264); (5) Other drugs/comorbidity, 4/10; 12% votes (31/264); (6) Experience of others/information-seeking/own research, 2/10; 2% votes (5/264); (7) Newness, 1/10; 2% votes (6/264); and (8) Convenience/frequency of use, 1/10; 1% votes (3/264).ConclusionsWe identified the patient perspective of choice between TNF versus non-TNF biologic for treating active RA. This knowledge can help in informative shared decision-making in clinical care.     

Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis and rheumatoid related osteoporosis

Objective

To study the role of VDR polymorphisms as risk factor for RA and osteoporosis, and whether osteoporosis complicating RA is due to RA or VDR polymorphisms.

Methods

VDR gene polymorphisms ApaI, TaqI, BsmI and FokI were typed by RFLP for 128 RA patients, 30 postmenopausal osteoporotic females and 150 healthy controls.

Results

Significant differences were found between patients and healthy controls in the frequency of BsmI and TaqI (Pc < 0.05) but no significant associations were found for FokI and ApaI polymorphisms except for aa genotype (Pc < 0.001). Titers of RF were higher with aa and bb genotypes. Anti-CCP and CRP levels were higher with aa genotype and more bone loss was associated with Bb genotype. Ff genotype frequency was higher in RA patients with osteoporosis than those without osteoporosis.

Conclusions

The ApaI, BsmI and TaqI polymorphisms may be a susceptibility risk factors for RA and the Ff genotype may be responsible for development of osteoporosis in RA Egyptian patients. However, the present study needs to be replicated in a large number of patients from allover the Egypt and also in multi-ethnic populations.     

不同DMARDs联合用药治疗类风湿关节炎疗效与安全性的研究

目的甲氨喋呤-来氟米特(MTX-LEF)二联和甲氨喋呤-氯喹-柳氮磺吡啶(MTX-CQ-SSZ)三联治疗活动性类风湿关节炎(rheumatoidarthritis,RA)1年的疗效和安全性比较。方法随访45例接受甲氨喋呤-来氟米特二联治疗和42例接受甲氨喋呤-氯喹-柳氮磺吡啶三联治疗的RA患者1a;比较两组患者治疗后不同时点各项疗效评价指标的改善情况,并记录不良反应。结果治疗1个月后,二联组各项指标及总体疗效的改善显著优于三联组;治疗后12个月二联组关节功能的改善显著优于三联组;血清RF﹥100I-U/mL且X线分期>I期的患者在治疗后6个月、12个月的疗效比较二联组显著优于三联组。所有患者耐受性好,不良事件发生率无显著性差异。结论两种联合用药方案均安全有效;MTX-LEF二联组起效早,对血清RF>100IU/mL且X线分期﹥I期患者疗效优于MTX-CQ-SSZ三联组。