Long-term Non-steroidal Anti-inflammatory Drugs Treatment Research Articles

Efficacy of long-term nonsteroidal antiinflammatory drug treatment on magnetic resonance imaging-determined bone marrow oedema in early, active axial spondyloarthritis patients.

To assess the efficacy of long-term treatment with nonsteroidal antiinflammatory drugs (NSAIDs) on bone marrow oedema (BMO) of the sacroiliac joint in newly diagnosed axial spondyloarthritis (SpA) with a symptom duration of less than 4years, a single-center, open-label study in a cohort of consecutive patients with newly diagnosed axial SpA was conducted. Eligible patients had magnetic resonance imaging (MRI)-determined BMO of the sacroiliac joint at baseline, had a symptom duration of less than 4years, and were naïve to NSAIDs. After the baseline MRI, an optimal dose of NSAID was administered for 24 or 48weeks. BMO of sacroiliac joint was quantified by applying the Spondyloarthritis Research Consortium of Canada (SPARCC) system. Disease activity was expressed using the Ankylosing Spondylitis Disease Activity Score (ASDAS). Primary end points were improvement in BMO of sacroiliac joint at week 24 or week 48. Forty-three patients were recruited, and 33 patients eventually completed the study, including 10 patients having follow-up MRI at week 24 and 23 patients having follow-up MRI at week 48. Overall, the mean of SPARCC score decreased from 21.8±16.1 at baseline to 10.2±12.8 at follow-up (p<0.001). 75.8% of the patients displayed a minimally important change, and 30.3% became free of BMO. The mean of ASDAS-CRP decreased from 3.1±1.0 at baseline to 2.1±1.0 at follow-up (p<0.001). Long-term treatment with optimal dose NSAIDs could significantly alleviate BMO of sacroiliac joint in early and active axial SpA.

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis.

The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

Nonsteroidal antiinflammatory drugs and prostaglandin E2 modulate the synthesis of osteoprotegerin and RANKL in the cartilage of patients with severe knee osteoarthritis

Although the osteoprotegerin (OPG)/RANK/RANKL system is the main modulator of bone remodeling, it remains unclear whether it is regulated in cartilage during osteoarthritis (OA). The aim of this study was to examine whether nonsteroidal antiinflammatory drug (NSAID) treatment modulates the synthesis of OPG and RANKL in the cartilage of patients with OA, and to investigate whether prostaglandin E(2) (PGE(2)) modifies this system in human OA chondrocytes in culture. A 3-month clinical trial was carried out in 20 patients with severe knee OA, all of whom were scheduled to undergo knee replacement surgery. Ten of these patients were treated with celecoxib, and the other 10 patients, who did not want to be treated, served as the control group. After surgery, cartilage was processed for molecular biology studies. We also used human OA chondrocytes to examine the effects of PGE(2) on OPG/RANKL synthesis, examining which surface receptors were affected by PGE(2). In patients with OA, celecoxib decreased RANKL synthesis in the cartilage, thereby increasing the OPG:RANKL ratio. In human OA chondrocytes in culture, PGE(2) elicited a dose- and time-dependent increase in the synthesis of RANKL, the extent of which was greater than that of OPG. Confocal microscopy revealed that PGE(2) induced RANKL transport to the cell membrane. Only EP2/EP4 agonists reproduced the effects of PGE(2) on OPG and RANKL induction. Long-term NSAID treatment inhibited the resorptive signal synthesized by chondrocytes. In vitro, PGE(2) regulated the expression and release of these key mediators of bone metabolism by articular chondrocytes. The role of OPG/RANK/RANKL in OA cartilage metabolism is still unknown, although the synthesis of these proteins would enable the cartilage to control the activity of subchondral bone cells.

The Impact of Occult Haemorrhage in Asymptomatic Endoscopic Peptic Ulcers On Long-Term Concomitant Use of NSAID and Low-Dose Aspirin

Purpose: Patients with rheumatoid arthritis(RA) display some of the risk factors for peptic ulcer(PU), and also have a high risk of cardiovascular disease. Therefore, determining the risk of PU induced by non-steroidal anti-inflammatory drugs(NSAIDs) alone or in combination with low-dose aspirin(L-aspirin) in the daily clinical setting of RA patients is essential. The primary objective of this study was to elucidate the risk of PU induced by concomitant L-aspirin in Japanese RA outpatients on long-term NSAID treatment. Although endoscopic PU(EPU) has been defined as an excavated mucosal break 3 mm in diameter in most studies, the clinical implications of EPUs are unclear. A secondary objective was thus to evaluate whether EPUs induced by NSAID/L-aspirin are associated with anemia, implying bleeding from PUs. Methods: This retrospective cohort study enrolled consecutive RA outpatients with a recorded medical history of >3 months. These patients underwent esophagogastroduodenoscopy. Subjects receiving PPI or prostaglandin E1 analog co-therapy or who displayed any changes in medication within the preceding 3 months were excluded from this investigation. Patients were then divided into 4 groups according to the pattern of NSAID/L-aspirin administration: controls(n=25); NSAID group(n=174); NSAID+Aspirin group(n=11); and NSAID+NSAID group(n=22). Hemoglobin level(Hb) and mean corpuscular volume(MCV) were used as biomarkers for potential bleeding. [Results]Ulcer incidence was 0% in the control group, 19.5% in the NSAID group, 18.2% in the NSAID+Aspirin group, and 45.5% in the NSAID+NSAID group. Ulcer incidence was higher in the NSAID group than in the control group(P=0.010), and ulcer incidence was higher in the NSAID+NSAID group than in the control or NSAID groups(P=0.010 and P=0.012, respectively). Conversely, no significant differences were seen in biomarkers for potential bleeding among the four groups. To clarify the association of EPUs with potential bleeding, each group was divided into two subgroups: with EPU; and without EPU. In subgroups with EPU, Hb was lower in the NSAID+Aspirin group than in the NSAID group or NSAID+NSAID group(P=0.010 and P=0.010, respectively). Furthermore, only in the NSAID+Aspirin group, Hb and MCV in the subgroup with EPU was lower in the subgroup with EPU than in the subgroup without EPU(P=0.055 and P=0.029). [Conclusions] Non-aspirin NSAID-duplicated therapy has a higher risk of EPU compared with NSAID alone, but L-aspirin-NSAID combination therapy does not. Nevertheless, EPUs with combined NSAID/L-aspirin therapy, but not in the other groups, seem to have a risk of potential bleeding, even if the EPUs are asymptomatic.

Bisphosphonate increases risk of gastroduodenal ulcer in rheumatoid arthritis patients on long-term nonsteroidal antiinflammatory drug therapy

Rheumatoid arthritis (RA) patients are at increased risk of peptic ulcers (PU) induced by nonsteroidal antiinflammatory drugs (NSAIDs). However, the impact of potential drug interactions on the development of PU has yet to be determined in a daily clinical setting. The aim was to estimate the clinical important interactions for PU presented by comedication in Japanese RA outpatients on long-term NSAID treatment. This retrospective cohort study enrolled 196 consecutive RA outpatients on NSAID medication for at least 3 months. Potential risk factors for endoscopic PU were analyzed in RA outpatients on longterm NSAID treatment. PU incidence was 31% with bisphosphonate co-therapy and 17% without the co-therapy. PU incidence was only 5% in subjects with proton pump inhibitors (PPI) or prostaglandin E1 analogues (PG) co-therapy, 14% with histamine-H(2) receptor antagonists(H2RA) co-therapy, and 27% without anti-ulcer agents. In multivariate logistic regression analysis, bisphosphonate co-therapy remained a significant risk factor for PU (OR, 2.29; 95% CI, 1.09-4.81). Other risk factors for ulcer development were advanced age (greater than 60 years) and smoking (OR, 2.58; 95% CI, 1.03-6.49 and OR, 2.71; 95% CI, 1.13-5.53, respectively.) Factors that significantly reduced the incidence of PU were H2RA or PPI/PG cotherapies (OR, 0.29; 95% CI, 0.12-0.68.). Bisphosphonate co-therapy as well as advanced age and smoking was found to be a significant risk factor in PU, while co-therapies of standard-dose H2RA or PPI/PG proved effective in preventing PU in Japanese RA patients on long-term NSAID treatment.

Long-term NSAID treatment directly decreases COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis

To simultaneously study the effect of a selective cyclooxygenase-2 (COX-2) inhibitor and that of a classic non-steroidal anti-inflammatory drug (NSAID) on the expression of pro-inflammatory genes in the cartilage of patients with severe knee osteoarthritis (OA) and in cultured human OA chondrocytes. A 3-month clinical trial was carried out on 30 patients with severe knee OA scheduled for knee replacement surgery. Patients were randomized into two groups: patients treated with celecoxib (CBX) and patients treated with aceclofenac (ACF). OA patients who did not want to be treated served as the control group. After surgery, cartilage was processed for molecular biology studies. We also employed cultured chondrocytes from different OA patients to examine NSAID effects on pro-inflammatory gene expression in cells stimulated with interleukin (IL)-1beta. Both CBX and ACF inhibited COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and inducible nitric oxide synthase (iNOS) synthesis in the articular cartilage of OA patients. In cultured chondrocytes, both NSAID decreased COX-2 and mPGES-1 synthesis and prostaglandin E2 (PGE2) release induced by IL-1beta, while no effect was observed on nitric oxide or iNOS synthesis. In OA patients, only CBX decreased tumor necrosis factor alpha and IL-1beta expression in the cartilage, while both NSAID diminished IL-1beta induced cytokine synthesis in cultured OA chondrocytes. Both NSAID diminished PGE2 release and induced a decrease in COX-2 and mPGES-1 synthesis in the cartilage from OA patients and in OA chondrocytes. These data suggest that prolonged therapy with PGE2 blocking agents decreases PGE2 production not only by direct inhibition of COX-2 activity, but also by down-regulating COX-2 and mPGES-1 synthesis in the cartilage. However, CBX and ACF seem to have a different anti-inflammatory profile in controlling pro-inflammatory gene expression in the cartilage.

Bisphosphonate Increases Risk of Peptic Ulcer in Rheumatoid Arthritis Patients On Long-Term Non-Steroidal Anti-Inflammatory Drug Therapy

Objective: Rheumatoid arthritis (RA) patients are at increased risk of developing peptic ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). However, despite the recent introduction of a variety of new drugs for the treatment of RA patients, the impact of potential drug interactions on the development of ulceration has yet to be determined in a daily clinical setting. The aim of the present study was to estimate the potential risks for peptic ulcer presented by co-medication in Japanese RA outpatients on long-term NSAID treatment. Methods: Our hospital-based cohort study enrolled 196 consecutive RA outpatients on NSAID medication for at least three months. The incidence of peptic ulcer was determined by esophagogastroduodenoscopy (EGD) from February 2003 to June 2006. Potential risk factors for developing peptic ulcer were evaluated by univariate and multivariate analysis. Results: Peptic ulcer was found in 43 (21.9%) out of 196 RA outpatients on long-term NSAID treatment. Peptic ulcer incidence was 31% with bisphosphonate co-therapy and 17% without co-therapy. peptic ulcer incidence was only 5% in subjects with proton pump inhibitors (PPI) or prostaglandin E1 analogs (PG) co-therapy, 14% with histamine-H2 receptor antagonists (H2RA) co-therapy, and 28% without anti-ulcer agents. In multivariate logistic regression analysis, bisphosphonate co-therapy remained a significant risk factor for peptic ulcer (OR, 2.36 versus non-users; 95% CI, 1.12-4.97; P = 0.024). Other risk factors for ulcer development were advanced age greater than 60 years and smoking (OR, 2.58; 95% CI, 1.03-6.48; P = 0.043 and OR, 2.72; 95% CI, 1.13-5.54; P = 0.026, respectively.) Factors that significantly reduced the incidence of ulceration were H2RA and PPI/PG co-therapies (OR, 0.33; 95% CI, 0.12-0.88; P = 0.027 and 0.09; 95% CI, 0.01-0.86; P = 0.037, respectively.) Conclusions: Bisphosphonate co-therapy was found to be a significant risk factor in peptic ulcer, while standard-dose H2RA as well as PPI/PG co-therapies proved effective in preventing gastroduodenal injuries in Japanese RA patients on long-term NSAID treatment.

Eradication of Helicobacter pylori Does Not Reduce the Incidence of Gastroduodenal Ulcers in Patients on Long‐term NSAID Treatment: Double‐Blind, Randomized, Placebo‐Controlled Trial

Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major causes of gastroduodenal ulcers. Studies on the benefit of eradication of H. pylori in NSAID users yielded conflicting results. To investigate whether H. pylori eradication in patients on long-term NSAIDs reduces the incidence of gastroduodenal ulcers. Patients on long-term NSAID treatment and who are H. pylori positive on serologic testing, were randomly assigned to either H. pylori eradication (omeprazole, amoxicillin, and clarithromycin) or placebo. Primary endpoint was the presence of endoscopic gastric or duodenal ulcers 3 months after randomization. One hundred sixty-five (48%) of a total of 347 patients were on gastroprotective medication. At endoscopy, gastroduodenal ulcers were diagnosed in 6 (4%) and 8 (5%) patients in the eradication and placebo group, respectively (p = .65). During follow-up of 12 months, no symptomatic ulcers or ulcer complications developed. No significant differences were found in the development of gastroduodenal erosions, dyspepsia, or in quality of life. H. pylori eradication therapy in patients on long-term NSAID treatment had no beneficial effect on the occurrence of ulcers, erosions, or dyspepsia. Ulcer rates in both study arms are remarkably low, in both patients with and without gastroprotective therapy.

Potential Risk of Bisphosphonates and the Protective Effect of Histamine-H2 Receptor Antagonists Against Peptic Ulcer Formation in Rheumatoid Arthritis Patients On Long-Term Non-Steroidal Anti-Inflammatory Drug Treatment

Potential Risk of Bisphosphonates and the Protective Effect of Histamine-H2 Receptor Antagonists Against Peptic Ulcer Formation in Rheumatoid Arthritis Patients On Long-Term Non-Steroidal Anti-Inflammatory Drug Treatment

Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial

Whether Helicobacter pylori increases the risk of ulcers in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) is controversial. We hypothesised that eradication of H pylori infection would reduce the risk of ulcers for patients starting long-term NSAID treatment. Patients were enrolled if they were NSAID naïve, had a positive urea breath test, had dyspepsia or an ulcer history, and required long-term NSAID treatment. They were randomly assigned omeprazole triple therapy (eradication group) or omeprazole with placebo antibiotics (placebo group) for 1 week. All patients were given diclofenac slow release 100 mg daily for 6 months from randomisation. Endoscopy was done at 6 months or if severe dyspepsia or gastrointestinal bleeding occurred. The primary endpoint was the probability of ulcers within 6 months. Analyses were by intention to treat. Of 210 arthritis patients screened, 128 (61%) were positive for H pylori. 102 patients were enrolled, and 100 were included in the intention-to-treat analysis. H pylori was eradicated in 90% of the eradication group and 6% of the placebo group. Five of 51 eradication-group patients and 15 of 49 placebo-group patients had ulcers. The 6-month probability of ulcers was 12.1% (95% CI 3.1-21.1) in the eradication group and 34.4% (21.1-47.7) in the placebo group (p=0.0085). The corresponding 6-month probabilities of complicated ulcers were 4.2% (1.3-9.7) and 27.1% (14.7-39.5; p=0.0026). Screening and treatment for H pylori infection significantly reduces the risk of ulcers for patients starting long-term NSAID treatment.

Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics but cause gastrointestinal injury. Present prophylactic measures are suboptimal and novel therapies are required. Bovine colostrum is a cheap, readily available source of growth factors, which reduces gastrointestinal injury in rats and mice. We therefore examined whether spray-dried, defatted colostrum could reduce the rise in gut permeability (a non-invasive marker of intestinal injury) caused by NSAIDs in volunteers and patients taking NSAIDs for clinical reasons. Healthy male volunteers (n=7) participated in a randomized crossover trial comparing changes in gut permeability (lactulose/rhamnose ratios) before and after 5 days of 50 mg of indomethacin three times daily (tds) per oral with colostrum (125 ml, tds) or whey protein (control) co-administration. A second study examined the effect of colostral and control solutions (125 ml, tds for 7 days) on gut permeability in patients (n=15) taking a substantial, regular dose of an NSAID for clinical reasons. For both studies, there was a 2 week washout period between treatment arms. In volunteers, indomethacin caused a 3-fold increase in gut permeability in the control arm (lactulose/rhamnose ratio 0.36+/-0.07 prior to indomethacin and 1.17+/-0.25 on day 5, P<0.01), whereas no significant increase in permeability was seen when colostrum was co-administered. In patients taking long-term NSAID treatment, initial permeability ratios were low (0.13+/-0.02), despite continuing on the drug, and permeability was not influenced by co-administration of test solutions. These studies provide preliminary evidence that bovine colostrum, which is already currently available as an over-the-counter preparation, may provide a novel approach to the prevention of NSAID-induced gastrointestinal damage in humans.

The gastroenterologist's caseloadcontribution of the rheumatologist

Rheumatological conditions often give rise to gastrointestinal (GI) symptoms, and vice versa, but the greatest point of contact between rheumatologists and gastroenterologists arises through gastrointestinal toxicity resulting from the use of nonsteroidal antiinflammatory drugs (NSAIDs). Standard NSAIDs are toxic to the entire GI tract. The point prevalence of ulcers in patients on long-term NSAID treatment is about 20% and the annual incidence of complications in these patients is 1% to 4%; 1,200 patients in the United Kingdom die each year as a result. Withdrawing NSAID treatment, or reducing the dose, is not always possible, and approximately 25% of patients require continued long-term antiinflammatory treatment. Misoprostol and acid-suppressing drugs such as ranitidine and omeprazole are helpful as prophylactic treatment in high risk patients, and in healing established ulcers, especially in patients carrying Helicobacter pylori, but there is a pressing need for new, safer antiinflammatory drugs to ease the burden of NSAID gastropathy. Selective inhibition of the COX-2 isoform of cyclooxygenase has been proposed as a new and safer therapeutic option. Clinical studies with meloxicam, a selective COX-2 inhibitor, support this view. Meloxicam has been extensively studied in arthritis patients and combines antiinflammatory efficacy with a lower incidence of GI toxicity than currently available NSAIDs.

Prevention of Nonsteroidal Anti-inflammatory Drug—Induced Gastrointestinal Mucosal Injury

The policy of prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury is still a matter of discussion. Indeed, no consensus exists as to whether cotherapy with histamine type 2 (H2) blockers or misoprostol is cost-effective. Placebo-controlled randomized clinical trials on the use of H2 blockers or misoprostol, as preventive agents (published between) January 1970 and December 1994), were identified through MEDLINE and reference lists from literature reviews. Crude rates of endoscopic lesions with short-term (< 2 weeks) and long-term (> 4 weeks) NSAID treatment were systematically assessed by 3 independent observers based on the intention-to-treat principle. The method of DerSimonian and Laird was used for pooling data. Heterogeneity was evaluated by using the Q statistic and the plots described by L'Abbe and colleagues. Twenty-four trials met the criteria for entry into the study. Gastric ulcer was found to be significantly reduced by misoprostol-both in short-term (pooled rate difference [RD], -13%, 95% confidence interval [CI], -26% to -1%) and long-term (RD, -8%; 95% CI, -18% to -1%) NSAID treatment-but not by H2 blockers. The risk for duodenal ulcer was significantly reduced by H2 blockers (RD, -2%; 95% CI, -5% to -0.2%) and by misoprostol (RD, -3%; 95% CI, -6% to -0.1%) in long-term but not in short-term administration. The use of misoprostol, but no that of H2 blockers, was beneficial in the prevention of NSAID-induced gastric ulcers. The number of patients to be treated to prevent 1 gastric ulcer with short- and long-term NSAID treatment is 11 and 15, respectively, for an intermediate baseline risk of 10%. Misoprostol and H2 blockers were beneficial in the long-term prevention of duodenal ulcers; misoprostol or H2 blockers in the short-term prevention of duodenal ulcers remains to be confirmed.

Effect of longterm misoprostol coadministration with non-steroidal anti-inflammatory drugs: a histological study.

Prostaglandins are widely used in the prevention and healing of non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers, but their longterm effect on the human gastric mucosa is unknown. This study assessed the effect of coadministration of prostaglandins with NSAIDs on the histology of the gastroduodenal mucosa. Histological appearances (using the Sydney system) of gastric biopsy specimens from 180 patients receiving longterm NSAID treatment of whom 90 had been receiving misoprostol (400-800 micrograms/day) for one to two years were studied. Both groups of patients were comparable with regard to clinical and demographic details. There was no significant difference (p > 0.1) in the prevalence of chronic gastritis (total, corpus or antrum only) between patients receiving (36 of 90 (40%)) or not receiving misoprostol (35 of 90 (39%)). Chronic gastritis was equally associated with the presence of Helicobacter pylori, 86% and 73% (p > 0.1), respectively, in the two groups. Significantly fewer patients receiving misoprostol had reactive gastritis than those receiving only NSAIDs (8 (9%) versus 27 (30%), p < 0.01). Reactive gastritis was not associated with H pylori. Thirty nine (43%) of the misoprostol treated patients had normal histology compared with 16 (18%) receiving only NSAIDs (p < 0.01). These results show two different patterns of gastric damage in patients receiving NSAIDs, namely chronic and reactive gastritis. Misoprostol treatment was associated with a significantly reduced prevalence of reactive gastritis and it is suggested that this, along with its antisecretory action, may explain the reduced prevalence of gastroduodenal lesions when coadministered with NSAIDs.

Prevalence of Helicobacter pylori infection and its effect on symptoms and non-steroidal anti-inflammatory drug induced gastrointestinal damage in patients with rheumatoid arthritis.

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter (H pylori) are both associated with an increased risk of peptic ulceration and gastropathy. It is not known, however, if there is an interaction between these two agents, and thus whether or not screening for H pylori before NSAID treatment is of value. The aim of this study was to find out if H pylori potentiates the damaging effects of NSAIDs. Fifty two patients with rheumatoid arthritis requiring longterm NSAID treatment were studied. Dyspeptic symptoms were assessed according to a standardised questionnaire. Gastroscopy was performed after a one week washout period during which NSAIDs were discontinued. Gastric and duodenal mucosal damage was graded endoscopically. H pylori was identified by biopsy urease test and by histological tests. Investigations were repeated after one month's treatment with an NSAID. Patients with H pylori infection (n = 26) had a higher dyspeptic symptom score (p < 0.05). One patient with duodenal ulcer (H pylori +ve) and two with endoscopic gastritis (both H pylori +ve) were excluded from further study. Forty two subjects completed the study. After treatment there was a rise in the gastric damage score both in the H pylori +ve (p = 0.06) and the H pylori -ve (p < 0.005) groups. There was no difference in the extent of increase in grade or the final grade at the end of the treatment period between the H pylori +ve and -ve patients. It is concluded that H pylori infection is associated with increased dyspeptic symptoms in patients receiving NSAIDs but that it does not potentiate NSAID gastropathy.