Continued Use Of Nonsteroidal Anti-inflammatory Drugs Research Articles

USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN PATIENTS WITH ADVANCED ACTIVE RHEUMATOID ARTHRITIS.

This study aimed to determine whether patients with active rheumatoid arthritis (RA) regularly take non-steroidal anti-inflammatory drugs (NSAIDs) and to clarify whether their decision to take NSAIDs depends on disease activity, intensity of pain, or functional status. The study also aimed to identify the risk factors for gastrointestinal side effects. Over 6 months, we conducted a cross-sectional single-center study of consecutively hospitalized patients with confirmed RA. Activities of daily living, pain intensity, and disease activity were evaluated by the Health Assessment Questionnaire, visual analog scale, and disease activity score, respectively, in 28 joints. Of 73 patients diagnosed with RA, 48 (66%) regularly took NSAIDs. Compared to non-users, NSAID users used glucocorticoids less frequently. The decision to use NSAIDs was independent of disease activity, pain intensity, degree of functional impairment, or presence of gastrointestinal risk factors. However, a higher degree of functional impairment was associated with a longer duration of continuous NSAID and glucocorticoid use. NSAIDs are still relevant for RA treatment. The decision to use them is not necessarily affected by disease activity or pain intensity, but their prolonged use is required in patients with a higher degree of functional disability. NSAIDs enable exclusion of glucocorticoid use, sparing patients of glucocorticoid-related side effects.

Association Between Long-Term Use of Non-steroidal Anti-inflammatory Drugs and Hyperkalemia in Diabetic Patients.

IntroductionThe association between continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) and hyperkalemia is not consistent in the literature and creates grounds for further large-scale trials, particularly in patients with a chronic disease that affects renal function, such as diabetes mellitus (DM). In this study, we will compare mean serum potassium level and the prevalence of hyperkalemia in diabetic and non-diabetic patients based on their use of NSAIDs.MethodsThis case-control study was conducted in the internal medicine unit of a tertiary care hospital from May 2019 to December 2020. After taking informed consent, 700 patients with a confirmed diagnosis of type 2 DM, of either gender, were enrolled in the study via consecutive convenient non-probability technique. Another set of 700 participants from the public were enrolled as the reference or control group. Continuous NSAID use was defined as NSAID used for a minimum of 20 days in the last 30 days. Blood was drawn via phlebotomy and sent to the laboratory to test for potassium level.ResultsSerum potassium level was significantly higher in diabetic patients with continuous NSAID use compared to the diabetic patients without continuous use (4.8 ± 0.8 mmol/L vs. 4.5 ± 0.7 mmol/L; p-value: 0.0001). Additionally, serum potassium level was significantly higher in non-diabetic patients with continuous NSAID use compared to non-diabetic patients without continuous use (4.3 ± 0.7 mmol/L vs. 3.9 ± 0.5 mmol/L; p-value: 0.0001) ConclusionIn this study, the patients with continuous use of NSAIDs had higher levels of serum potassium level compared to patients without continuous use of NSAIDs. This difference was even higher in diabetic patients.

Nonsteroidal Antiinflammatory Drug Use and Association With Incident Hypertension in Ankylosing Spondylitis.

Nonsteroidal antiinflammatory drugs (NSAIDs) increase blood pressure and potentially cardiovascular burden, which may limit their use in ankylosing spondylitis (AS). Our objective was to determine the association of NSAID use with incident hypertension in a longitudinal AS cohort. Adults with AS were enrolled in a prospective cohort study of patient outcomes and examined every 4-6 months. Hypertension was defined by patient-reported hypertension; antihypertensive medication use; or, on 2 consecutive visits, systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Continuous NSAID use was dichotomized based on the validated NSAID index. We assessed the association of NSAID use as a time-varying exposure with the incidence of hypertension using Cox proportional hazards models. Of the 1,282 patients in the cohort, 628 patients without baseline hypertension had at least 1 year of follow-up and were included in the analysis. Of these, 72% were male, the mean age at baseline was 39 ± 13 years, and 200 patients used NSAIDs continuously. On follow-up, 129 developed incident hypertension. After controlling for other variables, continuous NSAID use was associated with a hazard ratio of 1.12 for incident hypertension (95% confidence interval 1.04-1.20), compared to noncontinuous or no use. The association did not differ in subgroups defined by age, body mass index, biologic use, or disease activity. In our prospective, longitudinal AS cohort, continuous NSAID use was associated with a 12% increased risk for the development of incident hypertension, as compared to noncontinuous or no NSAID use.

Non-steroidal anti-inflammatory drugs in patients with stable ankylosing spondylitis receiving tumor necrosis factor inhibitor: continued vs withdrawn.

To investigate the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on disease activity in patients with stable ankylosing spondylitis (AS) receiving tumor necrosis factor inhibitor (TNFi). In this retrospective observational study, a total of 189 patients with stable AS receiving TNFi were included. Patients were classified into NSAID withdrawn group (n = 48) and NSAID continued group (n = 141), according to the use of NSAIDs. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured every 3months, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured every 6months as parameters to evaluate disease activity. ESR, CRP, and BASDAI at each time point, and time-averaged values of each parameter during the observation period of 1year were compared between the two groups. Repeated-measure ANOVA was performed to compare changes in disease activity parameters during the observation period between the two groups. The level of ESR, CRP, and BASDAI at baseline and during the observation period did not differ between the two groups. The time-averaged values of ESR (p = 0.096), CRP (p = 0.136), and BASDAI (p = 0.421), and changes of ESR (p = 0.101), CRP (p = 0.714), and BASDAI (p = 0.613) during the observation period were not significantly different between the two groups. The continued use of NSAIDs in patients with stable AS receiving TNFi had no additional benefit in controlling the disease activity, as compared to patients who withdrew NSAIDs. Considering the risk of toxicity of long-term NSAID use, withdrawal of NSAIDs in stable AS patients receiving TNFi may be preferable. Key points • There is a lack of supportive evidence whether to continue or withdraw non-steroidal anti-inflammatory drugs (NSAIDs) in patients with stable ankylosing spondylitis (AS) receiving tumor necrosis factor inhibitor (TNFi). • Compared with patients who withdrew NSAIDs, continuing NSAIDs in patients with stable AS receiving TNFi had no additional benefit in controlling disease activity. • The results of the present study provide evidence that supports withdrawal of NSAIDs in patients with stable AS receiving TNFi.

Disease-Modifying Effects of Long-Term and Continuous Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Spondyloarthritis

Spondyloarthritis or spondyloarthropathy (SpA) is a group of related rheumatic disorders, which presents with axial and nonaxial features, affecting structures within the musculoskeletal system, as well as other bodily systems. Both pharmacological and nonpharmacological therapeutic options are available for SpA. For decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been used as the first-line drugs to treat the disease. Research has shown that other than pain relief, NSAIDs have disease-modifying effects in SpA. However, to achieve these effects, continuous and/or long-term NSAID use is usually required. This review will give an overview of SpA, discuss NSAIDs and their disease-modifying effects in SpA, and highlight some of the important adverse effects of long-term and continuous NSAID use, particularly those related to the gastrointestinal, renal, and cardiovascular systems.

Efficacy of short term non steroidal anti-inflammatory drugs in Indian patients with axial spondyloarthritis

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the first-line drugs for axial spondyloarthritis because of their high efficacy in controlling symptoms. However, the review of the literature shows that among Caucasian patients, only ~ 1/3rd with recent disease onset and only ~10% with the long-standing disease achieved partial or complete remission. The present study was, therefore, aimed at finding out how many Indian axSpA patients achieved low-disease activity state or remission over a short period of 12 weeks. Methods: This was a retrospective study including 35 patients, both nonradiographic and radiographic axSpA, classified according to the Assessment of Spondyloarthritis International Society criteria (2009). Information was extracted from the electronic medical records for patients who had only received NSAIDs without any disease-modifying anti-rheumatic drugs or biologicals. The primary objective was to analyze the effect of continuous use of NSAIDs on their disease activity status as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) cutoff values at the baseline as compared to that after 3 months. Results: A total of 31/35 patients continuously treated with NSAIDs for 12 weeks showed statistically significant improvement in their disease activity status as measured by ASDAS-CRP (P Conclusion: NSAIDs are effective in reducing ASDAS-CRP disease activity status. The efficacy of NSAIDs observed in this study was much higher than that reported in European/North American patients. The reason for this difference needs further study.

Biomarkers of bone remodeling in ankylosing spondylitis patients using nonsteroidal anti-inflammatory drugs: results of an ETHICS research program

To evaluate changes in the concentration of biomarkers for osteoproliferation and bone resorption in ankylosing spondylitis (AS) patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) in different regimens. Forty patients with AS (according to the modified New York criteria), who had BASDAI ≥ 4.0 at baseline and at 52 weeks of on-demand NSAID treatment were examined and randomized into 2 groups: 1) 30 patients who used continuously oral tenoxicam 20 mg daily (a study group); 2) 10 patients who continued previous therapy (a comparison group). BASDAI and ASDAS were calculated; the serum levels of C-reactive protein, C-terminal type I procollagen propeptide (PICP), and C-terminal telopeptide of type I collagen (CTX-I) were measured at baseline and at 52 and 56 weeks of treatment. A control group consisted of 19 healthy volunteers. The continuous use of NSAIDs (tenoxicam) decreased higher baseline BASDAI and ASDAS scores. There were no changes in the indicators of AS activity in the patients who took on-demand NSAIDs. Baseline CTX-I levels did not differ between the patients with AS and the healthy individuals; those declined during continuous intake of tenoxicam and remained unchanged during on-demand administration. In the patients with AS, baseline PICP levels exceeded those in the healthy individuals. In the tenoxicam-treated patients, the concentrations of PICP at baseline and at 52 and 56 weeks were 17.1±9.0, 16.8±9.9, and 13.29±6.7 ng/ml, respectively (p=0.0001 for differences between the baseline and week 56 levels); in the comparison group, PICP levels did not change statistically significantly (p≥0.05 for all intergroup comparisons). Changing the inefficient long-term on-demand use of NSAIDs to their continuous intake is associated with a rapid decrease in clinical AS activity (within 4 weeks) with a reduction in the higher baseline concentration of the marker for osteoproliferation and in the normal level of the marker for bone resorption.

Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis).

Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis).

OP010. Medication-induced microscopic colitis: do recency and duration of use matter?

Background: Microscopic colitis (MC) is a colonic disorder characterised by chronic watery diarrhoea. There is increasing evidence (table present) that exposure to commonly prescribed drugs like non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), and statins is associated with an increased risk of MC. However, the attributive risk of recent or longer use and the effect of higher dosages has never been investigated, although this information would give more insight in the possible mechanism of medication-induced MC. Methods: A case-control study was conducted using the British Clinical Practice Research Datalink. Cases were diagnosed with microscopic, lymphocytic (LC) or collagenous (CC) colitis between 1992-2013. For each case, up to 5 randomly selected controls without MC were matched by year of birth, gender, and practice. The index date of the case defined that of the controls. Prescriptions within 60 days prior to index date were excluded to take into account a latency (lag) time and to minimize reverse causality. Exposure status was classified as current (61-90 days), recent (91-150 days), and past use (>150 days) according to the time since most recent prescription prior to index date. In current users, duration of continuous use and average daily dose was assessed. Conditional logistic regression analysis was applied to quantify the strength of the associations and to correct for confounders. Results: In total, 1.211 cases with MC (394 CC, 292 LC, 525 undefined MC) and 6.041 controls were identified. Current use of NSAIDs (OR 1.79, 95% CI 1.36-2.36), PPIs (OR 3.93, 95% CI 2.25-4.74), and SSRIs (OR 2.27, 95% CI 1.79-2.89) was associated with an increased risk of MC compared to never and past use. Especially a 4-12 months continuous use of NSAIDs, PPIs, and SSRIs increased the risk of MC. Long-term use (>24 months) attenuated this risk. Exposure to more than 1.25 standardised daily dosages was associated with an elevated risk of MC in PPI (OR 6.90, 95% CI 3.82-12.49) and SSRI users (OR 4.15, 95% CI 2.47-6.97). Analysis per MC subtype showed a positive association between current use of NSAIDs (OR 2.28, 95% CI 1.46-3.54) and PPIs (OR 6.15, 95% CI 4.41-8.58) in CC and current use of PPIs (OR 2.40, 95% CI 1.60-3.59) and SSRIs (OR 2.65, 95% CI 1.69-4.15) in LC. Statin use was not associated with MC. A sensitivity analysis with a lag time of 90 days showed conclusions consistent with the primary analysis. Conclusions: Use of NSAIDs, PPIs, and SSRIs is associated with an increased risk of MC. Especially in current users with a continuous exposure duration of 4 to 12 months, drug exposure as cause for MC should be considered.

SP0124 Advances in the Treatment of Spondyloarthritis

Spondyloarthritis (SpA) is a group of chronic inflammatory disease with either predominantly axial symptoms of the spine and sacroiliac joints (axial SpA) or predominantly arthritis (peripheral SpA), being anlylosing spondylitis...

Safety and Efficacy of On-demand Versus Continuous Use of Nonsteroidal Antiinflammatory Drugs in Patients with Inflammatory Arthritis: A Systematic Literature Review

To systematically review the efficacy and safety of on-demand versus continuous use of nonsteroidal antiinflammatory drugs (NSAID) in patients with inflammatory arthritis and to assess if longterm continuous treatment with NSAID in comparison with NSAID treatment on-demand reduces radiographic progression. A systematic literature review was performed in Medline, Embase, the Cochrane Library, and American College of Rheumatology/European League Against Rheumatism 2008-2009 meeting abstracts as part of the multinational 3e (Evidence, Expertise, Exchange) Initiative for generating practical recommendations about Pain Management by Pharmacotherapy in Inflammatory Arthritis. Articles fulfilling predefined inclusion criteria were reviewed and quality appraisal was performed. The search yielded a total of 1410 articles from Medline and Embase, 73 from Cochrane Central, and 3 meeting abstracts. After review, only one study fulfilled the defined inclusion criteria, which indicated that longterm continuous treatment with NSAID versus NSAID treatment on-demand reduced radiographic progression in patients with ankylosing spondylitis. Secondary measured endpoints were disease activity measures including pain and the frequency of observed adverse events in both groups. Relevant adverse events tended to occur more frequently in the continuous treatment group with odds ratios of 2.79 for hypertension, 1.67 for abdominal pain, 1.35 for diarrhea, 0.95 for dyspepsia, and 3.2 for depression. None of these differences were statistically significant, with the exception of depression, which could not be explained. Based on a single study, there does not seem to be a statistical difference in efficacy between the on-demand versus continuous use of NSAID in the context of ankylosing spondylitis. There were no studies in patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. Research is needed to study the risk-benefit ratio of continuous versus on-demand use of NSAID.

Imaging of axial spondyloarthritis including ankylosing spondylitis

New bone formation of the vertebral column is pathognomonic for ankylosing spondylitis (AS), while acute and/or chronic changes in the sacroiliac joints are relevant for diagnosis.The ‘gold standard’ for assessment...

Helicobacter pylori Eradication in Patients on Long-term Treatment With NSAIDs Reduces the Severity of Gastritis

Maintenance use of nonsteroidal anti-inflammatory drugs (NSAIDs) is often complicated by gastropathy. In non-NSAID users, eradication of Helicobacter pylori is associated with decreased mucosal inflammation, and may halt the progression to atrophy and intestinal metaplasia, but the continuous use of NSAIDs may interfere with these processes. To investigate the effect of H. pylori eradication on gastric mucosal histology during long-term NSAID use, with and without gastroprotective therapy. Patients were eligible for inclusion if they were on long-term NSAIDs and were H. pylori-positive on serologic testing. Patients were randomly assigned to either eradication or placebo. Gastritis was assessed according to the updated Sydney classification for activity, chronic inflammation, gastric glandular atrophy, intestinal metaplasia, and H. pylori density. Biopsy specimens were available for histology of 305 patients. Of these, 48% were on chronic gastroprotective medication. Significant less active gastritis, inflammation, and H. pylori density was found in the eradication group compared with the placebo group in both corpus and antrum (P<0.001). In the corpus, less atrophy was found in the eradication group compared with the placebo group. H. pylori eradication in patients on long-term NSAID therapy leads to healing of gastritis despite ongoing NSAID therapy.

Upper gastrointestinal disorders induced by non-steroidal anti-inflammatory drugs

We examined the characteristics of upper gastrointestinal disorders induced by non-steroidal anti-inflammatory drugs (NSAIDs). The questionnaire investigation was performed over a five year period. A study was performed on 354 patients (161 men and 193 women with mean ages of 66.0 and 70.7 years, respectively) who developed NSAIDs associated upper GI disorders: 21 patients had AGML, 212 had gastric ulcer, 63 had duodenal ulcer, 17 had gastroduodenal ulcers and 41 other cases. About 75 % of patients received NSAIDs for orthopedic conditions. Sixty percent of gastric disorders induced by NSAIDs affected the antrum or angulus of the stomach. The incidence of disorders of the gastric antrum was significantly higher in women than in men whilst the incidence of disorders on the gastric angulus was significantly higher in men than in women (p < 0.05). The proportion of patients with abdominal pain was significantly lower in patients over 65 years old than in those under 65 years old, and the proportion of patients with hematemesis or melena was significantly higher in patients over 80 years old than in those under 80 years old (p < 0.05). The time taken to achieve the healing stage was significantly longer in patients with greater than 3 months NSAIDs ingestion compared to patients that had received NSAIDs for less than 3 months (p < 0.05). Patients 65 years old and over with continuous NSAIDs use had asymptomatic ulcers, and patients 80 years old and over had hemorrhagic ulcers.

Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: A randomized clinical trial

A 2-year randomized controlled trial was performed to test the hypothesis that long-term, continuous treatment with nonsteroidal antiinflammatory drugs (NSAIDs), in comparison with NSAID treatment on demand only, influences radiographic progression in patients with ankylosing spondylitis (AS). Patients with AS (n = 215), who had previously participated in a 6-week, randomized, double-blind clinical trial that compared celecoxib, ketoprofen, and placebo, were randomly allocated to receive either continuous treatment with NSAIDs or on-demand treatment with NSAIDs for a period of 2 years. All patients began treatment with celecoxib, at a starting dosage of 100 mg twice daily; patients could increase this dosage to 200 mg twice daily or could switch to another NSAID while maintaining the same treatment strategy. Structural changes were assessed by radiographs of the lumbar and cervical spine and scored according to the modified Stoke Ankylosing Spondylitis Spine Score by one observer who was blinded to the treatment strategy and temporal order of the radiographs. Statistical analyses included a between-group comparison of 1) radiographic progression scores (by Mann-Whitney U test), 2) time-averaged values of variables reflecting signs and symptoms of AS (by linear regression analysis), and 3) the frequency of reported site-specific adverse events (by chi-square test or Fisher's exact test, as appropriate). Complete sets of radiographs were available for 76 of the 111 patients in the continuous-treatment group and for 74 of the 104 patients in the on-demand group. The mean +/- SD scores for radiographic progression were 0.4 +/- 1.7 in the continuous-treatment group and 1.5 +/- 2.5 in the on-demand treatment group (P = 0.002). Parameters reflecting signs and symptoms were not statistically significantly different between groups. The between-group difference in radiographic progression did not disappear after adjusting for baseline values of radiographic damage or disease activity variables and for time-averaged values of disease activity variables, nor after input of missing data. Relevant adverse events tended to occur more frequently in the continuous-treatment group than in the on-demand group (for hypertension, 9% versus 3%; for abdominal pain, 11% versus 6%; for dyspepsia, 41% versus 38%), but the differences were not statistically significant. A strategy of continuous use of NSAIDs reduces radiographic progression in symptomatic patients with AS, without increasing toxicity substantially.

Sodium Salicylate(NaSaL) Induces Apoptosis of NCI-H1299 Lung Carcinoma Cells via Activation Caspase-3 Protease

Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and/or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. Methods : A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and unclear staining(DAPI). The talytic activity of the caspase family was measured by the fluirigenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the death substrates(PARP and ICAD). Results : NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the population and unclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. Conclusion : NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.

Nonsteroidal anti-inflammatory drugs and cancer prevention.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, appear to have clinically significant anticarcinogenic effects in the gastrointestinal tract. Epidemiological data indicate that use of these drugs is inversely associated with the risk of sporadic colorectal cancer, and clinical trials among patients with familial polyposis coli show that NSAIDs can lead to the regression of large bowel adenomas. Animal studies have reported a similar efficacy of NSAIDs against experimental carcinogenesis. A consistent pattern in this research is that continued long-term use of NSAIDs is required for an anticancer effect--up to 15 or 20 years before a reduced risk of colorectal cancer appears. Epidemiological data also suggest possible protective effects in the stomach and esophagus. The mechanisms underlying any chemopreventive effect of NSAIDs are not clear. Inhibition of cyclooxygenase is one possibility, but pathways independent of cyclooxygenase and prostaglandins are also possible.

Treatment of Reactive Arthritis

AbstractReactive arthritis follows infections of the urogenital or enteric tract with bacteriasuch as Chlamydia, Yersinia, Shigella, Salmonella or Campylobacter. Typically,one knee or ankle are affected for weeks to several months, with up to 20% ofpatients experiencing a chronic course of more than 1 year. The acute arthritis is treated nonspecifically with nonsteroidal anti-inflammatorydrugs (NSAIDs), local measures such as arthrocentesis, cold pads and rest of theaffected joint. If the triggering bacterium can be isolated in Chlamydia-induced urogenital reactive arthritis, the infection should be treatedspecifically with antibacterials. Doxycycline 100mg twice daily, or erythromycin500mg 4 times daily, for 10 to 14 days are effective for Chlamydia,as is a single dose of azithromycin 1g. To prevent reinfections, the sexual partnershould be treated concurrently. Although remnants of bacteria and even bacterial RNA, suggesting live bacteria,can be demonstrated in the joint, treatment with antibacterials, even for long periods,does not show any benefit over placebo in enteric forms of reactive arthritis. For Chlamydia-induced reactive arthritis, antibacterials given for 3months in the absence of positive cultures from the urogenital tract may providesome benefit; however, further studies are needed before such treatment isrecommended. For reactive arthritis lasting longer than 6 months, patients may benefit fromsulfasalazine 2 g/day in addition to continued use of NSAIDs. In severalplacebo-controlled studies, sulfasalazine was well tolerated and moderately superiorto placebo. Other disease-modifying antirheumatic drugs (DMARDs) can be tried inindividual patients who do not respond to sulfasalazine. However, since nocontrolled studies are available to date for DMARDs other than sulfasalazine, therisk-benefit ratio of such treatment should be carefully discussed with the patient.

An endoscopic study of gastroduodenal lesions induced by nonsteroidal anti-inflammatory drugs

Rheumatoid arthritis (RA) and osteoarthritis (OA) are frequently treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Although NSAIDs are an effective therapy for the pain and inflammation of arthritis, they are associated with serious side effects, particularly ulceration, bleeding, and perforation of the gastrointestinal (GI) tract. In this study, 1826 OA or RA patients who either had been taking NSAIDS for ≥6 months or had been unable to tolerate continuous NSAID use because of adverse GI symptoms or suspected NSAID-related gastroduodenal lesions were examined endoscopically for gastroduodenal lesions and ulcers. At the same time, the patients were asked to rate the severity of any GI symptoms they had been experiencing. Of the total number of patients studied, 817 (44.7%) were OA patients with a mean (± SD) age of 55.8 ± 12.9 years, and 1009 (55.3%) were RA patients with a mean age of 53.1 ± 13.1 years. Clinically significant gastroduodenal lesions were found in 37.1% of patients (n = 678); of these, 24.0% (n = 439) had ulcers. Gastric ulcers were more frequent than duodenal ulcers (14.8% vs 10.2% of patients; P < 0.05), and most gastric ulcers (72.0%) were found in the antrum of the stomach. The prevalence of gastroduodenal ulcers increased with age ( P < 0.001), duration of OA ( P < 0.001), and duration of current NSAID use ( P = 0.019). The prevalence of gastroduodenal ulcers in patients taking NSAIDs for <1 year was 13.8%, compared with a nearly twofold higher prevalence (25.9%) in patients taking NSAIDs for periods of ≥1 year and up to 15 years. The prevalence of gastric ulcers was 32.6% in patients with a history of gastric ulcer but only 13.5% in patients with no GI history (previous gastric ulcer, duodenal ulcer, or upper GI hemorrhage). No relationship was found between the prevalence of gastroduodenal ulcers and sex (men, 22.4%; women, 24.9%) or prevalence of gastroduodenal ulcers and type of arthritic disease (RA, 23.6%; OA, 24.5%). The prevalence of gastroduodenal ulcers increased with the severity of GI symptoms ( P = 0.007). These results provide further endoscopic confirmation of the association between NSAID use and gastroduodenal lesions and ulcers and support the contention that safer treatment alternatives to conventional NSAIDs are required.

Nonsteroidal Anti-Inflammatory Drug-Associated Upper Gastrointestinal Lesions in Rheumatoid Arthritis Patients: Relationships to Gastric Histology, Helicobacter pylori Infection, and Other Risk Factors for Peptic Ulcer

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are risk factors for peptic ulcer in rheumatoid arthritis (RA) patients, but the contribution of reactive gastritis, concomitant Helicobacter pylori infection, or RA activity to NSAID ulcer pathogenesis is unknown. Methods: Ninety-six RA patients taking NSAIDs and dyspeptic sex- and age-matched control patients without NSAID use or an RA diagnosis were enrolled in the study. Results: Gastric ulcer (GU) was detected in 29 (30%) RA patients and 3 control patients (P < 0.001). Sixteen RA patients and no control patient had an H. pylori-negative GU. The GUs of the RA patients were mainly located in the prepyloric region (28%) and antrum (62%). Nine of the 29 RA patients (31%) with GU had more than 1 ulcer. Erosive gastropathy was detected in 34 (71% H. pylori-negative) RA patients and in 13 (62% H. pylori-negative) control subjects (P < 0.001). Chronic gastritis was observed in 65 RA patients (48% H. pylori-negative) and in 58 control subjects (43% H. pylori-negative) (NS), whereas reactive gastritis was found in only 2 RA patients and in none of the controls. Corticosteroid use was the only independent risk factor for GU: odds ratio was 6.8 (95% confidence interval, 1.3-36.0). The prevalences of duodenal ulcer or esophagitis were not increased in RA patients. Conclusions: RA patients using NSAIDs continuously are at a greatly increased risk of developing both H. pylori-negative and -positive GUs, and corticosteroid use is an independent risk factor for ulcer development. Most RA patients have chronic gastritis, whereas reactive gastritis is rarely associated with continuous NSAID use in RA patients.