Selective NSAIDs Research Articles

Cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs, manifested as urticaria and/or angioedema, anaphylaxis

BACKGROUND: The main mechanism of drug hypersensitivity to non-steroidal anti-inflammatory drugs is associated with inhibition of cyclooxygenase type 1, which leads to cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs from various subgroups of different chemical structures. Clinically, cross-hypersensitivity usually manifests in the form of urticaria and/or angioedema. AIM: To characterize a group of patients with cross-hypersensitivity to non-steroidal anti-inflammatory drugs manifesting as urticaria / angioedema / anaphylaxis. MATERIALS AND METHODS: To achieve this aim a prospective single-center study was conducted. Patients with a presumptive diagnosis of drug hypersensitivity to non-steroidal anti-inflammatory drugs (n=307) were consulted. A group of patients (n=237) with high probability of such reactions was identified, of which cross-hypersensitivity manifested as urticaria / angioedema / anaphylaxis was observed in 127 patients. This group was divided into 2 phenotypes: a group with concomitant chronic urticaria (n=67) and without it (n=60). We assessed demographic data, drug triggers, clinical manifestations, concomitant atopy, and compared these indicators between both groups. Selected patients underwent a drug provocation test with selective or predominantly selective non-steroidal anti-inflammatory drugs and paracetamol. RESULTS: Cross-hypersensitivity reactions manifested as urticaria / angioedema / anaphylaxis is the most common phenotype of immediate-type drug cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs (75.6%). Women develop this condition 2.5 times more frequently than men, and are more likely to develop cross-drug hypersensitivity with concomitant chronic urticaria with the onset of approximately 16 years later than men. Mild manifestations of cross-hypersensitivity (urticaria/angioedema) develop more frequently than severe ones (anaphylaxis). Angioedema in children, urticaria in adults with concomitant chronic urticaria and angioedema in adults without concomitant chronic urticaria are it's main manifestations. The most frequent non-steroidal anti-inflammatory drugs triggers are metamizole, acetylsalicylic acid and propionic acid derivatives. Non-steroidal anti-inflammatory drugs with the lowest risk of developing drug hypersensitivity are coxibs, paracetamol, and to a lesser extent ― meloxicam, nimesulide. CONCLUSION: The data obtained allowed us to expand our understanding of cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs presenting as urticaria/angioedema or anaphylaxis. Selective cyclooxygenase type 2 inhibitors and paracetamol are drugs with the highest safety profile.

Pharmacokinetic evaluation of oral deracoxib in geese (Anser anser domesticus).

The integration of pain management in veterinary practice, driven by heightened animal welfare concerns, extends to avian species where subtle and nonspecific behavioral signs pose challenges. Given that safety concerns with classical NSAIDs highlight the need for more targeted alternatives in birds, this study explores the pharmacokinetic (PK) properties of Deracoxib (DX), a COX-2 selective NSAID approved for use in dogs, following a single oral administration in geese. Six healthy female geese received 4 mg/kg DX. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma DX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software in a non-compartmental approach. The results indicated a terminal half-life of 6.3 h and a Tmax of 1 h, with no observed adverse effects. While refraining from claiming absolute safety based on a single dose, it is worth highlighting that further safety studies for DX in geese are warranted, suggesting a possibility for intermittent use. In addition, drawing conclusions on efficacy and suitability awaits further research, particularly in understanding COX-2 selectivity and protein binding characteristics specific to geese.

A blinded, randomized and controlled multicenter field study investigating the safety and efficacy of long-term use of enflicoxib in the treatment of naturally occurring osteoarthritis in client-owned dogs.

Enflicoxib is a COX-2 selective NSAID shown to be efficacious and safe in the treatment of pain and inflammation associated with canine osteoarthritis (OA) in clinical studies of 6 weeks duration. This prospective, multisite, blinded, randomized, placebo-controlled, parallel-group field study aimed to confirm the safety and efficacy of enflicoxib in long-term canine OA treatments. A total of 109 client owned dogs with clinical and radiographic signs of OA for at least 3 weeks were enrolled with 78 dogs completing all study visits. Dogs were randomized at a 3:1 ratio to receive enflicoxib (n = 83) or placebo (n = 26) once weekly during 6 months. Dogs underwent veterinary assessments from Day 0 to Day 189 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). Safety was assessed clinically and by repeated blood and urine sample analysis. The efficacy outcome measure was the treatment response according to the CSS and secondarily the treatment response according to the CBPI. The primary safety outcome was the incidence of adverse events (AEs) and secondarily the evolution of the clinical pathology parameters. Percentages of CSS responders for enflicoxib were 71.6; 74.6 and 71.6% on Days 44, 135 and 189 respectively, always showing statistically significant differences (p < 0.05) vs. placebo (41.7, 33.3, and 20.8% respectively). Treatment response according to owner assessments followed the same pattern, achieving significant differences compared to placebo after 2 weeks of treatment. The incidence and type of AEs were as described in previous enflicoxib studies of shorter duration and as for other NSAIDs, with no tendency to increase over time. No relevant changes in hematology, biochemistry or urine parameters were observed. Enflicoxib safety and efficacy profile is maintained after a long-term treatment, which together with its weekly administration, makes it a good alternative for the chronic treatment of dogs with naturally occurring OA.

Pain Management Strategies before Pan-Retinal Photocoagulation for Diabetic Retinopathy: A Systematic Review.

This systematic review aims to consolidate key findings regarding the efficacy of pain relief medications administered prior to pan-retinal photocoagulation (PRP) for diabetic retinopathy (DR). A comprehensive search of major databases from 1993 to 2023 was conducted. Clinical trials comparing pain relief drugs before PRP in patients diagnosed with DR requiring PRP treatment were eligible for inclusion. The assessment of pain scores involved the use of various scales, such as the visual analog scale (VAS), numerical rating scale (NRS), verbal rating scale (VRS), and other ordinal pain scales. In addition, laser parameters were taken into consideration during the analysis. Twenty-two clinical trials from initial 150 studies were included in the review. Nine studies evaluated the pain relief effects of nonsteroidal anti-inflammatories NSAIDs (selective NSAID and nonselective NSAID), two studies compared the effects of opioids (conventional opioids and atypical opioids), and eleven studies investigated the effects of benzodiazepines, lidocaine, and other sedatives. This review synthesizes findings from multiple studies reporting pain as an adverse outcome of PRP in patients with advanced DR. Based on the evidence from reviewed clinical trials, the administration of lidocaine 2% via transconjunctival, retrobulbar, or peribulbar block along with specific NSAIDs, such as topical ketorolac administrated 24 hours before treatment or oral diclofenac potassium (50 mg) prior to PRP, demonstrated beneficial effects among patients with DR.

Outcomes of hip fracture treatment with intravenous morphine and with other analgesics: postoperative analgesic medical expense, severity of pain and hospitalisation—a retrospective study

AimsThis study compares the postoperative medical costs and outcomes of hip fracture patients treated with intravenous (IV) versus other analgesics (weak opioids, NSAIDs or acetaminophen).MethodsWe performed a retrospective study at a tertiary hospital in Thailand, examining 1,531 patients who underwent hip fracture surgery between 2009 and 2020. We analyzed data on analgesic usage, costs, pain scores, and adverse effects.ResultsIn the study of 1531 patients, 63% of patients received as-needed analgesics, and 37% received preemptive prescriptions. In both groups, IV morphine was the predominant choice. The mean cost for the IV group was marginally higher than the other analgesics group ($2277 vs $2174). The other analgesics group had a significantly higher consumption of acetaminophen and selective NSAIDs (p = 0.004). Pain scores were similar across both groups, but the IV group had a significantly higher incidence of gastrointestinal side effects (24% vs 10.5%, p < 0.01).ConclusionThe choice of IV or other analgesics in treating hip fractures affects analgesic usage, side effects, medical costs, and patient outcomes. Further studies across different regions are recommended.

Factors Affecting Gastric Perforation Patient Outcome with History of Arthritis and Long Term Use of NSAIDs in Dr. Kariadi Semarang Period 2020 – 2022

Background: The incidence of gastric perforation gives a high mortality outcome. The second most common cause of gastric perforation is long-term use of NSAIDs. In cases of arthritis during the COVID-19 pandemic, a conservative therapeutic approach and administration of NSAIDs are preferred. Due to this, researchers want to know the factors affecting gastric perforation cause by NSAIDs. Method: An analytic descriptive study with a retrospective cohort study design, using electronic medical records of patients at RSUP Dr. Kariadi Semarang from January 2020 - December 2022. Data collected was in the form of demographics, diagnoses, procedures, preoperative conditions, scoring system, and outcome. Results: PULP score, one of prognostic factor, has a good level of significance compared to other scoring systems in determining the prognostic mortality of patients with gastric perforation. The combination of variables between the type of NSAIDs and the type of arthritis has a direct correlation with a positive inter-variable power of 86.7% and a significance of 0.049 on patient outcome. Conclusion: NSAIDs pose a risk of gastric perforation in long-term use. tNSAIDs carry a higher risk inducing gastric perforation than selective NSAIDs.

Effects of phenylbutazone, firocoxib, and dipyrone on the diuretic response to furosemide in horses.

Treatment with phenylbutazone (nonselective COX inhibitor) decreases the diuretic and natriuretic effects of furosemide by nearly 30% but the effects of COX-2 specific inhibitors (firocoxib) and atypical NSAIDs (dipyrone) are unknown. Furosemide-induced diuresis after pretreatment with firocoxib or dipyrone is diminished to a lesser extent than after pretreatment with phenylbutazone. Eight healthy mares. Each mare received 4 treatments in a prospective experimental crossover study using a replicated 4 × 4 Latin Square design: furosemide alone (FU), furosemide and phenylbutazone (PB), furosemide and firocoxib (FX), and furosemide and dipyrone (DP). After 24 hours of NSAID treatment at recommended dosages, ureteral catheters were placed for continual urine collection. After a 30-minute baseline collection period, furosemide (1.0 mg/kg, IV) was administered, and urine and blood samples were collected for 4 hours. Data were assessed by repeated measures ANOVA. Four-hour urine volume was (mean ± SD) ~25% less (P < .001) after pretreatment with all NSAIDs (PB 19.1 ± 2.1 mL/kg, FX 17.7 ± 3.5 mL/kg, DP 19.1 ± 3.9 mL/kg), as compared to FU (23.4 ± 5.1 mL/kg) (P < .001), but there were no differences between PB, FX, or DP. Interindividual variability in furosemide diuresis after pretreatment with different NSAIDs was observed. Though COX-2 selective NSAIDs and dipyrone might have less severe or fever gastrointestinal adverse effects in horses, our data suggest minimal differences in effects on furosemide-induced diuresis, and possibly, risk of nephrotoxicosis.

Prostaglandin E2 contributes to L. braziliensis survival and therapeutic failure in cutaneous leishmaniasis

ABSTRACT Patients with cutaneous leishmaniasis (CL) present an exacerbated inflammatory response associated with tissue damage and ulcer development. In recent years, higher rates of failure to pentavalent antimoniate therapy have been observed, yet the underlying reason remains poorly understood. We hypothesize that the eicosanoid PGE2 favours the establishment of infection by L. braziliensis, which contributes to therapeutic failure. The aim of the present study was to investigate the influence of PGE2 on the survival of L. braziliensis in macrophages and rates of therapeutic failure in CL patients. PGE2, an eicosanoid derived from the metabolism of arachidonic acid by the COX-2 enzyme, plays several roles in immune response. We found that increased PGE2 decreases the microbicidal function of macrophages and is associated with disease severity and therapeutic failure. Additionally, the neutralization of COX-2 by NS398, a selective NSAID, increases the ability of macrophages to kill L. braziliensis and protects against the pathological inflammatory response. Our data suggest that NS398 may serve as an adjunct treatment for CL patients.

Comparative structural study of selective and non-selective NSAIDs against the enzyme cyclooxygenase-2 through real-time molecular dynamics linked to post-dynamics MM-GBSA and e-pharmacophores mapping.

Inflammation-provoked disorders including cancer are arbitrated by cyclooxygenase-2 (COX-2). Celecoxib and niflumic acid are amongthe potent and selective inhibitors of this enzyme while aspirin (acetylsalicylic acid) and sodium salicylate are its non-selective and lesser potent inhibitors. Despite these proven studies, the comparative structural study of these selective and non-selective molecules at atomistic scale in complex state with COX-2 that may answer this differential inhibitory behavior has not been accomplished spotlighting the imperative need of additional research in this area. Thus, this study was framed to provide a strong explanation for the enigma of higher inhibitory activity of celecoxib-niflumic acid duo in comparison to aspirin and sodium salicylate towards COX-2. A contemporary approach including advanced molecular docking against COX2, molecular dynamics of receptor-ligand complexes, simulation-trajectory-backed MMGBSA for different time points, radius of gyration (Rg) calculations, and e-pharmacophores approach was employed to attain a rational conclusion. Our findings demonstrated the higher binding affinity of celecoxib and niflumic acid over aspirin and sodium salicylate against COX-2. Although both selective and non-selective COX-2 inhibitors manifested nearly the same stability in the active site of this enzyme but the e-pharmocophoric features found in the case of selective inhibitors scored over non-selective ones. Thus, our findings excluded the differential stability to be the cause of stronger potency of selective inhibitors but attributed their potency to greater number of complementary features present in these inhibitors against the active site of inflammation engendering COX-2.

A Concise Synthesis of Pyrrole-Based Drug Candidates from α-Hydroxyketones, 3-Oxobutanenitrile, and Anilines.

A simple and concise three-component synthesis of a key pyrrole framework was developed from the reaction between α-hydroxyketones, oxoacetonitriles, and anilines. The synthesis was used to obtain several pyrrole-based drug candidates, including COX-2 selective NSAID, antituberculosis lead candidates BM212, BM521, and BM533, as well as several analogues. This route has potential to obtain diverse libraries of these pyrrole candidates in a concise manner to develop optimum lead compounds.

Examination of the pharmacokinetics and differential inhibition of cyclooxygenase isoenzymes in New Zealand white rabbits (Oryctolagus cuniculus) by the Non-Steroidal anti-inflammatory Robenacoxib.

Effective rabbit analgesia is challenging, and there are few studies available on the newer COX-2 selective NSAIDs, such as robenacoxib. This study aimed to establish the pharmacokinetics of oral and subcutaneous robenacoxib, describe its inhibitory actions on COX enzymes, and develop dosing, using six healthy New Zealand white rabbits. Pharmacokinetics were determined from plasma concentrations after oral administration of robenacoxib (0.83-0.96 mg/kg) and also after subcutaneous administration (2mg/kg). The inhibitory actions of robenacoxib were evaluated by measuring plasma concentrations of thromboxane B2 (TBX2 ) and prostaglandin E2 (PGE2 ) as surrogate markers of cyclooxygenase enzyme isoform inhibition. The mean maximum concentration for oral and subcutaneous administration was 0.23 μg/ml and 5.82 μg/ml, respectively. Oral robenacoxib administration did not demonstrate a significant difference between any time point for PGE2 or TBX2 , though subcutaneous administration did for both. There was no significant difference in PGE2 or TBX2 concentrations at any time point when comparing subcutaneous versus oral routes. Although the results support that plasma robenacoxib exceeds the therapeutic levels compared to dogs and cats, there was little significance in the difference in the changes associated with COX-1 and COX-2 inhibition. Further studies are warranted to determine appropriate dosing, safety, and efficacy in rabbits.

Short-term administration of flunixin meglumine or firocoxib does not alter viscoelastic coagulation profiles in healthy horses

To evaluate the effect of the cyclooxygenase-2-selective NSAID firocoxib, compared to the nonselective NSAID flunixin meglumine on viscoelastic coagulation parameters in healthy horses. 12 healthy adult mixed-breed horses. Following a crossover protocol, horses were administered flunixin meglumine (1.1 mg/kg, IV, q 12 h for 5 days), allowed a 6-month washout period, and then administered firocoxib (0.3 mg/kg, PO, once, then 0.1 mg/kg, PO, q 24 h for 4 days). Omeprazole (1 mg/kg, PO, q 24 h) was administered concurrently with each NSAID. Viscoelastic coagulation profiles and traditional coagulation parameters (prothrombin time, partial thromboplastin time, and fibrinogen) were measured before and after each treatment. Viscoelastic coagulation parameters were within reference intervals before and after both treatments. There was a statistically significant difference between treatments for amplitude at 10 minutes after clot time (P = .02) and maximum clot formation (P = .02); however, the magnitude of change was not clinically significant. Short-term administration of flunixin meglumine and firocoxib did not result in significant alteration of viscoelastic coagulation profiles in healthy horses. However, clinicians should be aware of possible coagulopathy secondary to NSAID administration with long-term use or critical illness, and further study is indicated.

Prevalence and Impact of Potentially Inappropriate Medication Use on Post-Transplant Outcomes Among Older Adults with Plasma Cell Dyscrasias Receiving an Autologous Stem Cell Transplant

Background Polypharmacy and potentially inappropriate medication (PIM) use is a healthcare concern in older adults with cancer, predisposing them to multiple adverse outcomes. While there is no standard definition on the number of medications needed for polypharmacy, polypharmacy negatively impacts patient outcomes with an increase in adverse drug events, drug interactions, and hospitalizations. The prevalence and impact of PIM use on post-transplant outcomes among older adults with plasma cell dyscrasias (PCD) undergoing autologous stem-cell transplantation (ASCT) has not been adequately studied. Methods Using data from the Cancer and Aging Resilience Evaluation in Hematologic Malignancies (CARE-Heme) study, a single-center prospective observational registry of older adults with hematologic malignancies, we identified adults who were ≥50y at the time of referral to ASCT for plasma cell dyscrasia from January 2020 to March 2022. Eligible patients underwent a comprehensive geriatric assessment at the time of their pre-transplant visit along with a comprehensive review of their medication history by either a pharmacist, registered nurse, or physician. We defined polypharmacy as use of ≥5 medications and used the American Geriatrics Society (AGS) Beers 2019 criteria for assessment of PIM. The primary outcome was 30-day readmission following ASCT. Secondary outcomes included length of hospitalization during transplant, incident falls, and health related quality of life (HRQoL) (using PROMIS global 10 measure) at 90 days post-ASCT. Modified Poisson regression with robust variance estimator was used to compute adjusted relative risk of readmission and incident falls and multiple linear regression used to compute the adjusted mean difference of length of stay (LOS) and physical and mental HRQoL between those with one or more PIM use vs those without. All models were adjusted for age, sex, race (white vs other), comorbidity, frailty (using a 44-item deficit accumulation index) and melphalan dose. Results Of 112 adults enrolled in the registry, 101 proceeded with ASCT. The median age at transplant was 64 yrs (range 50-79); 59% were male and 58% were non-Hispanic white. The median number of medications was 9 (Interquartile range, IQR 6-12); 88% were taking ≥5 medications, whereas 57% were taking ≥9 medications. Overall, 38% (95% CI 28-48%) of the patients had evidence of at least one PIM (median 1, range 1-5). The prevalence of PIM was 26%, 43%, and 45% in the age groups 50-60 yrs, 60-70 yrs, and >70 yrs, respectively (Figure 1). The most prescribed PIM therapeutic category was anticholinergics (n = 15), non-cyclooxygenase selective oral NSAIDs (n= 10), skeletal muscle relaxants (n= 6), and central nervous system antidepressants (n = 6). Overall, 9% of patients were readmitted within 30 days whereas 16% of patients had falls within 90 days of ASCT. Patients with at least one PIM vs those without had an increased risk of readmission within 30 days (RR 6.07; 95%CI 1.01-36.7; p = 0.046). Furthermore, those with PIM vs without had a trend towards increased risk of falls (RR 2.13; 95%CI 0.86-5.32; p = 0.10) and worse physical (β -4.04; 95% CI -8.31-0.23; p = 0.06) and mental HRQoL (-3.65; 95% CI -7.61-0.31; p = 0.07) at 90 days. Meanwhile, there was no significant difference in the LOS index between the two groups (β 1.09; 95% CI -1.02-3.21; p = 0.30). (Table 1) Conclusion Our study showed a high prevalence of PIM use among older adults with PCD undergoing ASCT. Use of PIM was associated with a significantly increased risk of readmission and a trend towards increased risk of falls and worse HRQoL. Our findings are limited by our small sample size and need to be confirmed by larger studies that may pave the way for de-prescribing interventions to minimize PIM use in this population to improve post-transplantation outcomes of this vulnerable population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses.

Effective pain management in horses can be a challenge despite the understanding that appropriate analgesia improves animal welfare and increases treatment success. The administration of NSAID drugs, particularly phenylbutazone and flunixin, are common practice in equine veterinary patients. Known for their analgesic and anti-inflammatory properties, NSAIDs are used for the treatment of a variety of conditions in horses, from gastrointestinal to orthopedic pain. Despite extensive usage, NSAIDs have a narrow margin of safety and the body of literature documenting the efficacy and side effects of different NSAIDs is broad. The three main side effects associated with excessive or prolonged NSAID usage in horses include gastroduodenal ulceration, right dorsal colitis (RDC) and renal papillary necrosis. The use of cyclooxygenase-2 selective NSAIDS, such as firocoxib, are theoretically safer. The aim of this paper is to review the current literature on the use and efficacy of different NSAIDs, summarise the associated side effects of NSAID usage and evaluate the current state of knowledge for the diagnosis and treatment of such toxicities.

Non-steroidal anti-inflammatory drugs in equine orthopaedics.

SummaryOrthopaedic disorders are commonly encountered in equine veterinary medicine, and non‐steroidal anti‐inflammatory drugs (NSAIDs) play an important role in the management of many equine orthopaedic disorders. There are multiple NSAIDs available for use in horses, including both non‐selective and selective NSAIDS, and the body of literature evaluating the efficacy of these medications, their effects on normal and inflamed musculoskeletal tissues, and their side effects is broad. This review aims to summarise the current literature on the use of NSAIDs for equine orthopaedic disorders and examines new and future avenues for the management of inflammation in equine orthopaedics.

Design, synthesis, and pharmacological evaluation of novel and selective COX-2 inhibitors based on celecoxib scaffold supported with in vivo anti-inflammatory activity, ulcerogenic liability, ADME profiling and docking study

Four new series of 1,2,4 triazole derivatives 4a,b 5a-d, 6a-f, and 7a,b possessing methylsulphonylphenyl moiety as COX-2 pharmacophore were designed and synthesized. The target compounds were prepared and evaluated in-vitro against COX-1 and COX-2 enzymes. Compounds 4a, 5b, 6a, and 7a showed the highest selectivity towards the COX-2 enzyme (S.I. = 8.64–14.58) in comparison to celecoxib (S.I. = . 6.44). Interestingly, compounds 4a, 6a, and 7a showed good anti-inflammatory activity with edema inhibition (54.17, 53.03, and 50.29 %, in order) relative to the reference drug celecoxib (49.60%) after 3 h. Additionally, these potent derivatives 4a, 5b, 6a and 7a were significantly less ulcerogenic (U.I. = 2.27–2.97) than both reference drugs celecoxib (U.I. = 2.99) and indomethacin (U.I. = 20.25). Besides, a histopathological study of the stomach was also included. Moreover, docking simulation for the most selective compounds 4a, 5b, 6a, and 7a inside COX-2 active site was performed to explain their binding mode. Finally, an ADME study was applied and proved the promising activity of the new compounds as a new oral anti-inflammatory agent. In conclusion, the above findings reveal that newly developed compounds 4a, 6a, and 7a represent a potential selective COX-2 NSAID candidate with minimum gastrointestinal risks.

A Review on Various Analytical Methodologies for Etoricoxib

Etoricoxib belongs to the class of highly selective COX-2 inhibitor NSAIDs. It is mostly used for the treatment of pain, arthritic conditions including rheumatoid arthritis and osteoarthritis. The current study focuses primarily on analytical and bioanalytical method development methodologies, as well as numerous methods established for the estimation of etoricoxib, whether in pharmaceutical dose form or in bulk. Analytical procedures are critical for determining compositions, as they allow us to obtain both qualitative and quantitative results utilising advanced analytical tools. The analytical method for Etoricoxib may be chromatographic, electrochemical, spectral or hyphenated. These methods aid in the comprehension of critical process parameters as well as the minimization of their impact on precision and accuracy. Analytical method development is required to sustain high commercial product quality standards and to meet regulatory requirements. Following the reference, regulatory organisations in several nations have established standards and procedures for providing approval, authentication, and registration. Bioanalytical methods are designed to quantify the concentration of drug, metabolite, or typical biomarkers from various biological fluids including serum, urine, saliva and tissue extracts.

Assessment of TRM-201 (Rofecoxib) Efficacy and Safety for Chronic Pain in Hemophilic Arthropathy: The Rofecoxib Efficacy and Safety Evaluation Trial in Hemophilic Arthropathy (RESET-HA), a Randomized, Double-Blind Placebo-Controlled Phase III Clinical Trial

Assessment of TRM-201 (Rofecoxib) Efficacy and Safety for Chronic Pain in Hemophilic Arthropathy: The Rofecoxib Efficacy and Safety Evaluation Trial in Hemophilic Arthropathy (RESET-HA), a Randomized, Double-Blind Placebo-Controlled Phase III Clinical Trial

Profile of Pain Medication Use in Hemophilia and Hemarthrosis: An Analysis of a Pharmacy Claims Database

Introduction: Chronic joint pain associated with bleeding disorders (particularly Hemophilia A and Hemophilia B) is well characterized. The most common treatments reported by patients with bleeding disorders include acetaminophen, traditional nonsteroidal anti-inflammatory drugs (tNSAIDs; cyclooxygenase 1/2 inhibitors, COX-1/2), COX-2 selective NSAIDs, and opioids (Witkop, et al. Haemophilia . 2017;23:556). Up to 50% of patients have reported opioid use to manage both acute and chronic pain(Witkop, et al. Haemophilia . 2017;23:556). The aim of this study was to compare and analyze different types of prescription pain medications in patients with a diagnosis of hemophilia A, B, and hemarthrosis using a pharmacy claims database. Methods: A cross-sectional analysis was conducted on a retrospective cohort of patients with bleeding disorders receiving pain medications in the Truven Health MarketScan Commercial Claims and Encounters database, for which IRB approval was not required. Index encounters were reported from April 1, 2017 to March 30, 2018, with one year of follow up. Patients were outpatients, inpatients, or both. Patient-level demographics were not collected. Results: Unique patients totaling 876 received 5,702 prescriptions. Patient diagnosis codes included Hemophilia A (D66), Hemophilia B (D67), and hemarthrosis (M362), each of which contributed 79.2%, 11.9%, and 8.8%, respectively, to the total prescriptions. Outpatient prescriptions comprised 81.0% of total prescriptions. Scheduled prescriptions comprised 70.8% of all prescriptions, 81.7% of inpatient prescriptions, and 68.2% of outpatient prescriptions (see Table). Schedule II drugs comprised 82.6% and 77.3% of all scheduled inpatient and outpatient prescriptions, respectively (see Table). Schedule IV prescriptions were the next most common, followed by schedule III. Prescription NSAIDs were more common in the outpatient than in the inpatient setting (see Table). Among NSAIDs, celecoxib comprised approximately half of the outpatient NSAID prescriptions and 15.1% of all outpatient prescriptions. Discussion: Regardless of setting, schedule II drugs are the most common form of pain management prescription in patients with hemophilia or hemarthrosis. Prescriptions for scheduled medications appear similar to what might be inferred in previous studies of patient reported use (Witkop, et al. Haemophilia . 2017;23:556). Consistent with self-reports (Witkop, et al. Haemophilia . 2017;23:556), hydrocodone or oxycodone with acetaminophen were confirmed to be the most frequently prescribed schedule II opioids. tNSAIDs, such as those reported in this analysis share gastrointestinal (GI) bleeding risk which may be heightened in persons with hemophilia compared with those who have no bleeding disorders. Celecoxib represents approximately 50% of outpatient NSAID prescriptions in this analysis despite data showing its clinically significant GI event risk is similar to both ibuprofen and naproxen (Nissen, et al. N Engl J Med. 2016:2519). Over-the counter acetaminophen is commonly used to treat chronic joint pain in hemophilia (Witkop, et al. Haemophilia. 2017;23:556) presumably to avoid GI bleeding, yet is reported to be less efficacious than celecoxib (Rodriguez-Merchan, et al. Blood Rev. 2018: 116). The broad use of opioids with their attendant risk of misuse, addiction, and diversion; as well as tNSAIDs, with their attendant GI risks, underscores the limited pain management options available for persons with hemophilia. This cross-sectional prescription claims data analysis highlights the need to identify and develop alternate forms of chronic pain medications for this population who have unique unmet needs (Humphries, et al. Haemophilia. 2015:41). [Display omitted] DisclosuresHelm: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Buckner: Genetech: Honoraria; Spark: Honoraria; Sanofi: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; American Thrombosis: Membership on an entity's Board of Directors or advisory committees; Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria; CSL Behring: Honoraria; Tremeau Pharmaceuticals: Consultancy, Honoraria; uniQure: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria. Macgregor: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Boice: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Cerasoli: RX Medical Dynamics LLC: Consultancy, Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Khan: Rx Medical Dynamics, LLC: Current Employment. Argoff: Tremeau Pharmaceuticals,Inc: Consultancy.

Efficacy and safety of enflicoxib for treatment of canine osteoarthritis: A 6-week randomised, controlled, blind, multicentre clinical trial.

Enflicoxib is a new COX-2 selective NSAID intended for the treatment of pain and inflammation associated with canine osteoarthritis. A prospective, multisite, blinded, randomised, controlled, parallel-group field study was performed to determine the efficacy and safety of enflicoxib in canine osteoarthritis. A total of 242 dogs were randomised to receive enflicoxib at 4 or 2mg/kg, mavacoxib at 2mg/kg or placebo, orally. Enflicoxib and placebo were administered once weekly from day 0 to day 35. Mavacoxib was administered on D0 and day 14. Veterinarians assessed efficacy with a numerical rating scale and owners used the Canine Brief Pain Inventory. After 6 weeks, enflicoxib at 4mg/kg showed the highest percentage of responders as assessed by the veterinarians (68%) and the owners (84%), followed by mavacoxib (62and 83%, respectively), and enflicoxib at 2mg/kg (57 and 80%, respectively). All treatments reached statistical significance versus placebo, which obtained success rates of 37% and 53%, respectively. No differences in the incidence of adverse reactions were detected among the different groups. Enflicoxib administered weekly for 6 weeks, at 4mg/kg PO with an initial loading dose of 8mg/kg, is efficacious and safe for the treatment of canine osteoarthritis.