Previous Nonsteroidal Anti-inflammatory Drug Research Articles

A Good Response to Nonsteroidal Antiinflammatory Drugs Does Not Discriminate Patients With Longstanding Axial Spondyloarthritis From Controls With Chronic Back Pain.

To compare the response to nonsteroidal antiinflammatory drugs (NSAIDs) in patients with longstanding axial spondyloarthritis (axSpA) and controls with back pain (nonspondyloarthritis [non-SpA]). Consecutive outpatients with chronic back pain (axSpA or non-SpA), were prospectively recruited. Any previous NSAIDs were withdrawn 2 days before study start (baseline). Back pain was assessed using a numerical rating scale (NRS; range 0-10) starting at 2 hours after baseline and several times thereafter up to 4 weeks. "Any response" to NSAIDs was defined as improvement of back pain on the NRS > 2 units, and "good response" as improvement > 50%, compared to baseline. Among 233 patients included, 68 had axSpA (29.2%) and 165 had non-SpA back pain (70.8%). The mean age was 42.7 (SD 10.7) vs 49.3 (SD 11.1) years, symptom duration 15.1 (SD 11.1) years vs 14.6 (SD 11.9) years, and pain score 5.9 (SD 2.3) vs 6.3 (SD 2.0), respectively. Overall, of patients with axSpA or non-SpA back pain, 30.9% vs 29.1% of patients showed any response and 23.5% vs 16.4% of patients showed a good response after 4 weeks, respectively (P value not significant). No differences were found in the rapidity of response or between subgroups of patients based on demographics, including different stages of axSpA. No major differences in the response to NSAIDs were found between patients with axSpA and those with non-SpA with longstanding chronic back pain. The item in the Assessment of SpondyloArthritis international Society classification criteria on "response to NSAIDs" needs more study.

Real-World Postmarketing Study of the Impact of Adalimumab Treatment on Work Productivity and Activity Impairment in Patients with Psoriatic Arthritis.

IntroductionThis study investigated the effectiveness of adalimumab treatment in improving Work Productivity and Activity Impairment (WPAI) in patients with psoriatic arthritis (PsA) in real-world settings in Japan.MethodsThis 24-week, single-arm, postmarketing surveillance study (2014–2017), conducted at 75 centers in Japan, enrolled adalimumab-naïve patients (paid workers, including part-time) meeting ClASsification criteria for Psoriatic ARthritis (CASPAR). The primary endpoint was improvement in overall work impairment (OWI) scores from baseline to week 24. Secondary endpoints included changes in WPAI-PsA (OWI, absenteeism, presenteeism, and activity impairment), Psoriasis Area and Severity Index (PASI), psoriatic arthritis screening and evaluation (PASE) scores, Disease Activity Scores in 28 joints using C-reactive protein (DAS28[CRP]), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and PASI75/90 and American College of Rheumatology (ACR) 20/50/70 rates.ResultsIn the effectiveness population (n = 106; 72.6% men; mean ± standard deviation [SD] age, 49.3 ± 10.7 years), OWI scores significantly improved (mean ± SD change, − 25.2 ± 35.3; p < 0.0001) from baseline to week 24. Other WPAI domain scores also improved significantly. Changes in OWI were significantly correlated (p < 0.0001) with PASE (r = 0.6284), DAS28(CRP) (r = 0.6059), BASDAI (r = 0.7281), and HAQ-DI (r = 0.6161) scores and were significantly influenced by previous nonsteroidal anti-inflammatory drug use (p = 0.0142), and baseline PASE (p = 0.0098), DAS28(CRP) (p = 0.0026), HAQ-DI (p = 0.0004), and BASDAI (p < 0.0001) scores. At the last evaluation, rate (95% confidence interval) of PASI 75 and 90 (n = 100) was 58.0% (47.7–67.8) and 39.0% (29.4–49.3), respectively, and that of ACR 20, 50, and 70 (n = 58) was 86.2% (74.6–93.9), 70.7% (57.3–81.9), and 53.4% (39.9–66.7), respectively. No new safety signals were observed in the safety population (n = 148).ConclusionAdalimumab treatment improved WPAI in patients with PsA. Improvements in OWI and joint symptoms were significantly associated.Trial Registration NumberClinicalTrials.gov identifier: NCT02414633.FundingAbbVie GK and Eisai Co., Ltd.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0866-y) contains supplementary material, which is available to authorized users.

A pilot randomised blinded placebo-controlled trial of paracetamol for later treatment of a patent ductus arteriosus.

To explore the efficacy and risks of oral paracetamol in later (>2 weeks old) treatment of patent ductus arteriosus (PDA). Amulticentre double-blind placebo-controlled randomised pilottrial in three neonatal intensive care units in Australia. Infants born <33 weeks with haemodynamically significant PDA were treated with a 5-day course of oral paracetamol or placebo. Cardiac ultrasounds were used to document haemodynamic parameters. The primary outcome analysed was ductal closure by 48 h after treatment completion. Secondary outcomes included reduction in ductal diameter >25% and safety. Fifty-five infants were enrolled, of whom 27 received paracetamol and 28 placebo. Eighty percent hadreceived previous non-steroidal anti-inflammatory drug. Mean postnatal age was 25 days. Four of the 27 ducts treated with paracetamol closed vs. 0/28 treatedwith placebo (p = 0.05). An additional 13/27 given paracetamol vs. 7/28 givenplacebo showed significant constriction (p = 0.008). No adverse effects were observed . There was some evidence of increased closure with oral paracetamol at postnatal age >2 weeks; however, the overall efficacy was not high.

Evaluation of two doses of etoricoxib, a COX-2 selective non-steroidal anti-inflammatory drug (NSAID), in the treatment of Rheumatoid Arthritis in a double-blind, randomized controlled trial.

BackgroundTreatment with non-steroidal anti-inflammatory drugs (NSAID) is a common component of treatment regimens for rheumatoid arthritis (RA). Etoricoxib is a COX-2 selective NSAID that has demonstrated efficacy in the treatment of RA at a dose of 90 mg. The current study further evaluated the efficacy of etoricoxib 60 mg and 90 mg in RA patients with active disease.MethodsThis was a 2-part, double-blind, placebo-controlled study in RA (NCT01208181). Patients were required to have a diagnosis of RA (according to ARA 1987 revised classification criteria) and were to demonstrate symptom flare upon discontinuation of previous NSAID treatment prior to randomization. Part I was a 6-week, placebo-controlled period to assess the efficacy of etoricoxib 90 mg and etoricoxib 60 mg, each compared to placebo, as well as to each other. Part II was a 6-week period to evaluate the potential benefit of dose escalation from etoricoxib 60 mg to etoricoxib 90 mg after 6 weeks exposure to etoricoxib 60 mg in Part I compared to maintaining a steady dose of etoricoxib 60 mg throughout Parts I and II. Primary endpoints were Disease Activity Score evaluating 28 joints and C reactive protein level (DAS28-CRP) index and Patient Global Assessment of Pain (Pain) score (0–100 mm VAS) after 6 weeks of treatment in Part I. Adverse events were monitored throughout the study.ResultsIn total, 1404 patients were randomized in a 2:7:7:8 ratio; 1228 patients completed Part I and 713 patients continued to Part II. Both etoricoxib doses were superior to placebo on both primary efficacy endpoints (p = 0.004 for 60 mg and p = 0.034 for 90 mg for DAS28-CRP; p < 0.001 for both doses for PGAP) in Part I. Further in Part I, etoricoxib 90 mg was not significantly different from 60 mg for DAS28-CRP, but did demonstrate a small, but statistically significant decrease in baseline PGAP score vs. 60 mg (p = 0.019). In Part II, there was no significant decrease in PGAP score after increasing to 90 mg in subjects with inadequate pain relief on 60 mg as compared to subjects who stayed on 60 mg. The incidence of AEs and SAEs were similar between etoricoxib 60 mg and 90 mg in both Part I and II.ConclusionBoth etoricoxib 90 mg and 60 mg are superior to placebo in relieving the symptoms of RA. Etoricoxib 90 mg vs 60 mg resulted in a statistically significant, though small, improvement in PGAP score, but not DAS28-CRP. Dose escalation from 60 mg to 90 mg in pain inadequate responders did not significantly improve efficacy. These results confirm the efficacy and tolerability of etoricoxib 90mg in patients with RA. In addition, this study demonstrated that etoricoxib 60 mg is also efficacious and well-tolerated in RA.Clinical Trial RegistrationNCT01208181 (registered September 22, 2010).Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1170-0) contains supplementary material, which is available to authorized users.

Risks of nonsteroidal antiinflammatory drugs in undiagnosed intensive care unit pneumococcal pneumonia: Younger and more severely affected patients

PurposeThe purpose of this study is to investigate whether exposure to nonsteroidal antiinflammatory drugs (NSAIDs) at the early stage of severe pneumococcal community-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission may affect its presentation and outcome. Material and methodsMedical records of ICU adult patients (12-year period) with a pneumococcal CAP diagnosis were retrospectively analyzed according to previous NSAID exposure. ResultsOne hundred six confirmed pneumococcal CAP were identified, 20 received NSAIDs within 4 (2-6) days before admission. Nonsteroidal antiinflammatory drug–exposed patients were younger (43.3 vs 62.2 years; P < .0001), had less frequently at least one chronic comorbid condition (40% vs 75%; P = .003), had more often complicated pleural effusions (20% vs 2.3%; P = .01), and more frequent pleuropulmonary complications (odds ratio: 5.75 [1.97-16.76]). Nonsteroidal antiinflammatory drug patients required more often noninvasive ventilatory support (25% vs 4.6%; P = .003). Intensive care unit length of stay and mortality were similar. ConclusionsWe report as severe pneumococcal pneumonia in young and healthy patients exposed to NSAIDs as in older, more comorbid, and nonexposed ones. Nonsteroidal antiinflammatory drug use may mask initial symptoms and delay antimicrobial therapy, thus predisposing to worse outcomes.

A66: Assessment of Radiographic Progression in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Tocilizumab: 2‐Year Results From the TENDER Trial

Background/Purpose: A phase 3 trial (TENDER) demonstrated the efficacy of the interleukin-6 receptor inhibitor tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA) ([1, 2]). The aim of this study was to investigate the progression of radiographic joint damage in patients with sJIA treated with TCZ for up to 2 years in TENDER. Methods: One hundred twelve patients 2 to 17 years old with active, refractory sJIA of ≥6 months' duration and inadequate response to previous nonsteroidal anti-inflammatory drugs and oral corticosteroids were enrolled in TENDER. Patients were randomly assigned 2:1 to receive TCZ according to body weight (12 mg/kg <30 kg or 8 mg/kg ≥30 kg) or placebo intravenously every 2 weeks for 12 weeks. Patients then received open-label TCZ in the ongoing long-term extension. Radiographic progression was calculated as change in adapted Sharp/van der Heijde score (aSH) score and/or Poznanski score, assessed on hand and wrist radiographs, from baseline to weeks 52 and 104. Radiographic progression was indicated by a positive aSH score change or a negative Poznanski score change. Clinical efficacy end points included American College of Rheumatology (ACR) Pediatric (Pedi) 70/90 responses. Results: Baseline and ≥1 postbaseline aSH and Poznanski scores were available for 47 and 33 patients, respectively (reasons for missing x-rays: early withdrawal, no consent, unreadable x-rays). Baseline characteristics for patients with radiographic data were similar in the whole TCZ population (1). Patients with assessable aSH/Poznanski scores had 5.2-/4.8-year disease duration, 21.3/19.2 active joints, 20.0/18.2 joints with limitation of movement, and 53.9/59.2 mm/h erythrocyte sedimentation rate. At weeks 52 and 104, 20 and 19 patients, respectively, had aSH progression, and 8 and 8 patients, respectively, had Poznanski score progression. Median changes in aSH score from baseline to weeks 52 and 104 were 0 and 0.5, respectively (1). Median changes in Poznanski score from baseline to weeks 52 and 104 were 0.29 and 0.16, respectively (1). Table 1. Week 52 Week 104 a IQR, interquartile range. aSH score (n = 47), median (IQR) 0.00 (−8.70: 4.00) 0.50 (−7.50: 12.00) Poznanski score (n = 33), median (IQR) 0.29 (−0.05: 1.05) 0.16 (−0.01: 1.04) ACR Pedi 70 (n = 112), n/N (%) 92/106 (86.8) 57/65 (87.7) ACR Pedi 90 (n = 112), n/N (%) 67/106 (63.2) 46/65 (70.8) Conclusion: Although changes in radiographic scores over time were seen in many patients, on average, patients with sJIA did not experience noticeable progression of radiographic damage over 2 years of treatment with TCZ.

Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS)

ObjectiveTo evaluate efficacy and safety of ustekinumab in patients with ankylosing spondylitis (AS).MethodsIn this prospective, open-label, single-arm, proof-of-concept clinical trial (ClinicalTrials.gov identifier NCT01330901), ustekinumab in a dose of 90 mg...

Use of etoricoxib in patients with gout in real clinical practice

Objective: to evaluate the efficacy and safety of etoricoxib (Arcoxia ®) in gouty patients with an acute arthritis attack in real clinical practice. Subjects and methods. Thirty patients (25 men and 5 women; mean age 52.4±13.5 years) with crystal-verified gout participated in the pilot open-label study of the patients with arthritis, including those who had taken other nonsteroidal anti-inflammatory drugs (NSAIDs) without any effect. All the patients received etoricoxib (Arcoxia ®) in a dose of 120 mg/day for 7 days and, if arthritis persisted, in a dose of 90 mg/day for 7 more days. The authors estimated an articular index, swelling and hyperemia indices, resting and movement pain by a visual analogue scale (VAS), therapy tolerance in the patient's opinion before and 7 days after therapy and, in the patients taking etoricoxib for 14 days, after 14 days of therapy. Biochemical and clinical blood tests were carried out at the first and subsequent visits. Results. Seven days after therapy, an arthritis attack was abolished in 24 of the 28 patients, following 14 days, arthritis persisted only in 1 patient, but the number of affected joints reduced from 8 to 2. Following 7 days, there was a reduction in the mean erythrocyte sedimentation rate from 37.2+10.2 (before etoricoxib intake) to 15.3±8.3 mm/h (p<0.001), VAS resting pain from 48.6±21.4 to 5.2±3.5 mm (p<0.001), swelling (p<0.001) and hyperemia (p< 0.001) indices, and articular index (p<0.001). In 2 patients with baseline uncontrolled arterial hypertension, the drug was discontinued because of elevated blood pressure; periorbital edema was noted in one case by the end of a therapy course. There were no increases in the serum levels of liver enzymes, in the concentrations of creatinine and urea, and in glomerular filtration rate. Conclusion. Etoricoxib (Arcoxia ®) is highly effective and safe when used in patients with acute gouty arthritis, including those who had not benefited from previous NSAID therapy and those with oligoand polyarthritis.

SAT0438 Catch-Up Growth During Tocilizumab Therapy for Systemic Juvenile Idiopathic Arthritis: 2-Year Data from a Phase 3 Clinical Trial

BackgroundSystemic juvenile idiopathic arthritis (sJIA), characterised by chronic arthritis associated with prominent systemic features, has a significant impact on the growing skeleton, resulting in impaired linear growth and systemic osteoporosis....

Methodology of a large prospective, randomised, open, blinded endpoint streamlined safety study of celecoxib versus traditional non-steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis: protocol of the standard care versus celecoxib outcome trial (SCOT)

IntroductionCyclooxygenase 2 (COX-2) inhibitors have less upper gastrointestinal toxicity than traditional non-steroidal anti-inflammatory drugs (NSAIDs). However, both COX-2 inhibitors and traditional NSAIDs may be associated with adverse cardiovascular side effects....

Provocation tests with the offending nonsteroidal anti-inflammatory drugs in patients with urticaria/angioedema reactions

The provocation test (PT) with the suspected drug represents the gold standard in the diagnosis of non-IgE hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Nevertheless, there is no consensus regarding the clinical management of suspected NSAID-sensitive patients. This study assessed if a PT with the suspected drug is a reliable and safe proceeding to confirm NSAID hypersensitivity in patients with a clinical history of urticaria/angioedema (Urt/AE). It also analyzed different patient characteristics (such as gender, age, atopy, dermographism, time interval between the last drug reaction, and number of previous NSAID reactions) in relation to PT positivity. One hundred fifty-nine patients with Urt/AE apparently related to assumption of one or more NSAIDs underwent PT with the suspected drugs. Moreover, to distinguish single/multiple NSAID reactivity in patients who did not tolerate the offending NSAID, another strong cyclooxygenase-1 inhibitor PT was performed. PT was negative in 142/159 patients (89.31%), ruling out a diagnosis of NSAIDs hypersensitivity; 17/159 patients (10.69%) experienced a reaction of Urt/AE during the PT: 8 patients were diagnosed as single reactors to NSAIDs and 4 as multiple reactors to NSAIDs. Those with a history of multiple NSAID reactions and male patients were both more likely to have a positive PT. Our results suggest that in all patients with history of NSAID cutaneous reactions, the NSAID hypersensitivity should be confirmed by an oral PT and that the diagnostic proceeding can safely start with the offending NSAID.

Long-Term Follow-Up of 1,000 Patients Cured of Helicobacter pylori Infection Following an Episode of Peptic Ulcer Bleeding

To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients. Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up. Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up. Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

The association between pain intensity and the prescription of analgesics and non-steroidal anti-inflammatory drugs.

BackgroundIt is not known whether general practitioners (GPs) prescribe analgesic medication according to intensity of pain or a hierarchical prescribing regimen.AimsThe aim of this study was to assess the association of strength of pain-relief medication prescribed by the GP with the strength of previous prescription and pain level.MethodsThe PROG-RES study collected data on pain intensity in 428 patients aged ≥50 years with non-inflammatory musculoskeletal pain during a consultation with their GP. Prescriptions for analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) were identified on the day of the consultation and in the previous year and were classified as basic, moderate or strong analgesic or NSAID. Regression models were used to assess the association of strength of analgesia and prescription of a NSAID with the strength of previous prescription and the level of pain.ResultsThe majority of patients were not prescribed medication for their pain at the index consultation, but had such a prescription the previous year. There was an association between strength of analgesic and intensity of pain: more intense pain resulted in a stronger drug. This association was attenuated by adjustment for prescribed analgesia in the previous year. There was no association between intensity of pain and NSAID prescription, but previous NSAID prescription predicted another such prescription.ConclusionGPs do not always issue prescriptions for musculoskeletal pain. In cases where a prescription is issued, this is more strongly influenced by previous prescriptions than the patient's pain level. GPs adopt an individualized approach to the treatment of musculoskeletal pain in older adults.

Modification du spectre de l’allergie aux protéines de transfert lipidique par les anti-inflammatoires non-stéroïdiens

The major allergens of rosaceae are pathogenesis related proteins that are secreted to protect the plant against phytopathogenic fungus. Pru p3, a lipid transfer protein (LTP) is one of peach major allergens. A 38 year-old woman had a history of isolated peach allergy since the childhood (contact urticaria). Consumption of peeled peaches and other rosaceae was well tolerated. She occasionally took non-steroidal anti-inflammatory drugs (NSAIDs) on demand for migraine. She presented anaphylactic symptoms three hours after nectarine consumption. She had taken ketoprofen before meal. Positive skin prick tests were observed for peach, nectarine, plum and cherry. Specific IgE to Pru p3 were positive, specific IgE for other peach allergens remained negative. Challenge test with nectarine alone and NSAID alone were negative. We hypothesized that intake of NSAID before fruit eating may have increased the level of LTP allergen in the serum, leading to clinical manifestations. A similar mechanism has already been described in food anaphylaxis due to wheat with previous NSAID intake.

Development of an injection site sarcoma shortly after meloxicam injection in an unvaccinated cat

A single dose of a rapidly-absorbed non-steroidal anti-inflammatory drug (NSAID) was injected into the subcutaneous tissue of the interscapular region of a 12.5-year-old cat. A mild swelling was noticed at the injection site 6 weeks later. This progressed into a 5 cm diameter mass which was removed 6 months after the injection had been given. An injection site sarcoma (ISS) was diagnosed histologically. As the cat had not been vaccinated for at least 12 years, the previous NSAID injection was considered to be a possible cause of the ISS. Inflammation is thought to be important in the development of ISS. If injection of a rapidly-absorbed NSAID can stimulate sufficient inflammation to promote the development of an ISS, other non-vaccine injections may also have the potential to influence ISS development. This suggests that injection of both vaccines and non-vaccine medications should be minimised to reduce the risk of ISS development.

A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee.

Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA). Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI) scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment.

Concordance between prescriber‐ and patient‐reported previous medical history and NSAID indication in the CADEUS cohort

Various data sources may be used in pharmacoepidemiological studies. When they cannot be obtained from valid databases, medical data must be obtained from physicians or patients. In the CADEUS study, both patients and their prescribers reported medical data allowing investigation of the concordance between these sources. CADEUS is a French national cohort study of traditional non-steroidal anti-inflammatory drug (NSAID) and coxib users conducted between September 2003 and August 2004 in France that employed self-administered questionnaires to obtain medical data from patients and their prescribers. The Kappa statistic (kappa) was used to measure concordance between patients and prescribers in 18 530 pairs with regard to previous medical history and index NSAID indication. For previous medical history, the proportion of agreement ranged from 70.7 to 99.2% and concordance was: substantial (kappa = 0.61-0.80) for hypertension, myocardial infarction, stroke and diabetes; moderate (kappa = 0.41-0.60) for angina pectoris, peripheral arterial disease and hypercholesterolaemia; fair (kappa = 0.21-0.40) for unstable angina, cardiac insufficiency, dyspepsia, gastroesophageal reflux and gastric ulcer; slight (kappa < 0.21) for upper gastrointestinal haemorrhage. For index NSAID indication, the proportion of agreement ranged from 84.3 to 99.4% and concordance was almost perfect (kappa = 0.81-1.00) for inflammatory rheumatism, flu-like symptoms, dysmenorrhoea and dental pain; substantial for arthritis, back pain and headache; moderate for osteoarticular pain. Concordance was better for specific or serious conditions both regarding previous medical history and indication. Prescriber or patient perception and understanding may reduce concordance for certain items.

GOAL: multicenter, open-label, post-marketing study of flavocoxid, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin

Objectives:GOAL (Gauging Osteoarthritis [OA] with Limbrel*Limbrel is manufactured by Primus Pharmaceuticals, Inc., Scottsdale, AZ, USA.), an open-label, post-marketing study was performed to determine the overall efficacy and gastrointestinal (GI) tolerability of flavocoxid, a novel, plant-based, anti-inflammatory medication, in a ‘real world’ clinical practice setting. To this end, the study enrolled several unique patient types including nonsteroidal anti-inflammatory drug (NSAID) naïve patients, those who had used NSAIDs in the past, regardless of outcome (positive or negative), and those who had previously taken a gastroprotective medication to improve GI tolerability or continued to take it as a precautionary measure to prevent NSAID-associated GI damage.Methods:A total of 1067 individuals at 41 rheumatology practices were enrolled and prescribed flavocoxid, 500 mg b.i.d., for 60 days. The Physician Global Assessment of Disease (PGAD) visual analog scale (VAS) was used as a global measure to assess the signs and symptoms of OA, including joint discomfort, functional stiffness, functional mobility and quality of life. In addition, overall tolerability and upper GI tolerability were assessed by individual questions scored on a 5-part Likert scale. The physicians also monitored any interruption in, or cessation of use of flavocoxid due to a GI issue as well as changes in the use of gastroprotective medications. Adverse event (AE) monitoring was also conducted.Results:Of the 1005 patients who completed all follow-up visits, physicians recorded an average improvement in VAS scores from 60.1 ± 18.8 at baseline to 42.5 ± 21.9 at 8 weeks (p < 0.001) in 65.8% of patients. The PGAD VAS noted the most significant improvement in those patients with moderate to severe OA (baseline VAS [0 = least severe, 100 = most severe]: 0–25mm, −3.5 ± 6.9; 26–50 mm, −10.1 ± 17.0; 51–75 mm, −19.3 ± 19.5; 76–100 mm, −29.6 ± 23.6; p < 0.001) and in those patients who were historically non-responders to NSAIDs (40.3 ± 21.1 vs. 66.3 ± 17.7 at baseline; p < 0.001). Patients who had previously responded well to NSAIDs had VAS scores of 42.6 ± 19.8 vs. 58.0 ± 18.0 (p < 0.001) and NSAID naïve subjects showed improvement in VAS scores from 60.5 ± 18.0 at baseline to 46.3 ± 23.7 (p < 0.001). The study recorded a low incidence (∼10%) of AEs reported to physicians and good overall tolerability to flavocoxid. Flavocoxid showed improved upper GI tolerability in almost 50% of previous NSAID users (p < 0.001) and reduced therapy interruption in ∼90% of previous NSAID users with a history of GI-related therapy interruptions (p < 0.0001). Finally, the use of flavocoxid resulted in a >30% reduction in or cessation of the use of gastroprotective medications such as proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2s) in subjects (p < 0.001).Conclusions:Within a ‘real world’ clinical rheumatology practice setting, flavocoxid demonstrated significant efficacy in the management of OA in multiple patient types and displayed significant potential for reducing the possibility of adverse GI side-effects and use of gastroprotective agents associated with more traditional OA medications. A limitation of this study was that it was open-label and not rigorously controlled. The large population may compensate for this lack of control.

Postmarketing cohort study to assess the safety profile of oral dexketoprofen trometamol for mild to moderate acute pain treatment in primary care

Recently, new concerns on the safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) have been raised by the European Medicines Agency (EMEA) and other regulatory authorities. The safety profile of oral dexketoprofen trometamol for the treatment of acute mild to moderate pain of different causes in actual conditions of use in the primary care setting was assessed. A prospective cohort study was designed to evaluate the tolerability of dexketoprofen compared with other commonly prescribed analgesics. Medications were given according to specifications in the summary of product characteristics. The intensity of pain was assessed at baseline and at days 1 and 7 of drug treatment using a 100-mm visual analog scale (VAS). Adverse events (AEs) were recorded. A total of 7,337 patients (median age [IQR] = 46 [33-61] years) were included in the study comparing dexketoprofen (n = 5,429), diclofenac (n = 485), ibuprofen (n = 479), paracetamol (n = 459), metamizole (n = 207), aceclofenac (n = 103), naproxen (n = 74), piroxicam (n = 69) and dexibuprofen (n = 32). The reasons for use were: musculoskeletal disorders, headache, dysmenorrhea and odontalgia. Treatment compliance was very high. Metamizole-paracetamol and dexketoprofen showed the lowest prevalence of AEs (2.7% and 3.6%, respectively), while aceclofenac-diclofenac showed the highest prevalence (8.2%) (P < 0.0001). AEs most frequently observed during NSAID treatment were those related to the gastrointestinal tract (3.5% of subjects, 84% of all AEs), followed by AEs related to the nervous system (0.4%) and skin (0.1%). Most of the reported AEs (91.3%) were of mild to moderate intensity (303 of 332) and only 3.3% of them were considered severe (11 of 332). Risks for gastrointestinal AEs were adjusted for age, gender, history of previous NSAID intake, gastroprotective drugs and reason for prescription. Taking metamizole-paracetamol as the reference group, the odds ratios (OR, 95%) were: 1.30 (0.77-2.19) for dexketoprofen, 1.57 (0.79-3.13) for ibuprofen and dexibuprofen, 2.31 (0.64-8.27) for naproxen, 2.63 (0.85-8.15) for piroxicam and 3.37 (1.87-6.06) for aceclofenac-diclofenac. These results confirm the safety of oral treatment with dexketoprofen in patients with acute pain of various etiologies observed in previous studies and support the use of dexketoprofen as a first-line drug for the approved therapeutic indications.

Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding

Aim: To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long-term study including more than 400 patients. Methods: Patients with peptic ulcer bleeding were prospectively included. H. pylori infection was confirmed by rapid urease test, histology or 13 C-urea breath test. Several eradication regimens were used. Ranitidine 150 mg was administered daily until eradication was confirmed by breath test 8 weeks after completing eradication therapy. Patients with therapy failure received a second or third course of therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy, and were controlled yearly with a repeated breath test. Results: Four hundred and twenty-two patients were followed up for at least 12 months, with a total of 906 patient-years of follow up. Mean age was 59 years, and 35% were previous nonsteroidal anti-inflammatory drug (NSAID) users. Sixty-nine percent had duodenal, 24% gastric, and 7% pyloric ulcer. Recurrence of bleeding was demonstrated in two patients at 1 year (incidence: 0.22% per patient-year of follow up), which occurred after NSAID use in both cases. Conclusion: Peptic ulcer rebleeding does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved.