Pirfenidone use in fibrotic diseases: What do we know so far?

BACKGROUND: Pirfenidone has demonstrated significant anti-inflammatory and antifibrotic effects in both animal models and some clinical trials. Its potential for antifibrotic activity positions it as a promising candidate for the treatment of various fibrotic diseases. Pirfenidone exerts several pleiotropic and anti-inflammatory effects through different molecular pathways, attenuating multiple inflammatory processes, including the secretion of pro-inflammatory cytokines, apoptosis, and fibroblast activation. OBJECTIVE: To present the current evidence of pirfenidone's effects on several fibrotic diseases, with a focus on its potential as a therapeutic option for managing chronic fibrotic conditions. FINDINGS: Pirfenidone has been extensively studied for idiopathic pulmonary fibrosis, showing a favorable impact and forming part of the current treatment regimen for this disease. Additionally, pirfenidone appears to have beneficial effects on similar fibrotic diseases such as interstitial lung disease, myocardial fibrosis, glomerulopathies, aberrant skin scarring, chronic liver disease, and other fibrotic disorders. CONCLUSION: Given the increasing incidence of chronic fibrotic conditions, pirfenidone emerges as a potential therapeutic option for these patients. However, further clinical trials are necessary to confirm its therapeutic efficacy in various fibrotic diseases. This review aims to highlight the current evidence of pirfenidone's effects in multiple fibrotic conditions.

Nonsurgical therapy for lumbar spinal stenosis caused by ligamentum flavum hypertrophy: A review.

Lumbar spinal stenosis (LSS) can cause a range of cauda equina symptoms, including lower back and leg pain, numbness, and intermittent claudication. This disease affects approximately 103 million people worldwide, particularly the elderly, and can seriously compromise their health and well-being. Ligamentum flavum hypertrophy (LFH) is one of the main contributing factors to this disease. Surgical treatment is currently recommended for LSS caused by LFH. For patients who do not meet the criteria for surgery, symptom relief can be achieved by using oral nonsteroidal anti-inflammatory drugs (NSAIDs) and epidural steroid injections. Exercise therapy and needle knife can also help to reduce the effects of mechanical stress. However, the effectiveness of these methods varies, and targeting the delay in LF hypertrophy is challenging. Therefore, further research and development of new drugs is necessary to address this issue. Several new drugs, including cyclopamine and N-acetyl-l-cysteine, are currently undergoing testing and may serve as new treatments for LSS caused by LFH.

Gout: A Rapid Review of Presentation, Diagnosis and Management.

Gout is inflammatory arthritis caused by monosodium urate crystal deposition in articular and non-articular structures. Acute gout flares are often monoarticular/polyarticular involving lower extremity joints characteristically involving 1st metatarsophalangeal joint. However, gout flares can also be polyarticular, involving upper extremity joints, especially in patients with multiple comorbidities and contraindications to urate-lowering therapies (ULT). Risk factors exacerbating gout flares include obesity, high alcohol and purine-rich food consumption, and the use of diuretics. Diagnosis requires synovial fluid analysis with direct visualization of monosodium urate crystals. Acute flares are managed with steroids, non-steroidal anti-inflammatory drugs, or colchicine. Long-term management includes lifestyle modifications including a heavy emphasis on weight loss, avoidance of alcohol, purine-rich foods, and diuretics. ULT is indicated in patients with 2 or more gout flares/year, tophi, or radiographic evidence of gouty arthropathy. Although allopurinol is the first-line ULT agent, it does carry a risk of inducing severe cutaneous adverse reactions, especially in patients with chronic kidney disease and patients harboring the HLA-B*5801 allele. Other ULT agents include febuxostat and probenecid. ULT is usually titrated to achieve goal serum uric acid (SUA) levels below 6 mg/dL. However, in patients with tophi, a lower SUA target of less than 5 mg/dL should be implemented for prompt urate crystal dissolution.

Activity of apremilast in a patient with severe pemphigus vulgaris: case report.

Introduction: Although the treatment for pemphigus vulgaris (PV) has been revolutionized by the use of rituximab combined with corticosteroids, new effective therapies with a better safety profile are needed. Observation: A 67-year-old woman was diagnosed with severe mucosal PV, which was initially misdiagnosed as atypical Behçet's disease. Following an unsuccessful colchicine treatment, significant improvement was observed upon the introduction of apremilast: reduced pain, fewer lesions, and a stabilized weight. The discontinuation of apremilast led to a rapid relapse. Retrospective analysis through anti-Dsg3 ELISA indicated a gradual decrease in antibody levels during the apremilast treatment. Discussion: Apremilast, a phosphodiesterase 4 inhibitor approved for psoriasis and Behçet's disease's related oral ulcers treatment, demonstrated its efficacy in this PV case. This is the second case report highlighting the effectiveness of apremilast for PV treatment. Apremilast's ability to upregulate cyclic adenosine monophosphate (cAMP) levels appears to contribute to the stabilization of keratinocyte adhesion. Conclusion: Apremilast may be a promising therapeutic option for the treatment of pemphigus, with an innovative mechanism of action, no induced immunosuppression, and good tolerance. It could be a good alternative to steroids, in the treatment regimen of steroids combined with rituximab.

Nitroglycerin combined with NSAIDs for prevention of post-ERCP pancreatitis: A meta-analysis of prospective, randomized, controlled trials.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. OBJECTIVE: A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. METHODS: Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. RESULTS: A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. CONCLUSION: GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.

Nonsteroidal Anti-Inflammatory Drugs and Experimental Chagas Disease: An Unsolved Question.

Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi with an acute, detectable blood parasites phase and a chronic phase, in which the parasitemia is not observable, but cardiac and gastrointestinal consequences are possible. Mice are the principal host used in experimental Chagas disease but reproduce the human infection depending on the animal and parasite strain, besides dose and route of administration. Lipidic mediators are tremendously involved in the pathogenesis of T. cruzi infection, meaning the prostaglandins and thromboxane, which participate in the immunosuppression characteristic of the acute phase. Thus, the eicosanoids inhibition caused by the nonsteroidal anti-inflammatory drugs (NSAIDs) alters the dynamic of the disease in the experimental models, both in vitro and in vivo, which can explain the participation of the different mediators in infection. However, marked differences are founded in the various NSAIDs existing because of the varied routes blocked by the drugs. So, knowing the results in the experimental models of Chagas disease with or without the NSAIDs helps comprehend the pathogenesis of this infection, which still needs a better understanding.

The therapeutic benefits of NSAIDs and physical therapy in knee osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) has been established as a progressive wear and tear disease of the synovial joints, which also involves a certain degree of inflammation. Considering there is no disease modifying medication available at the moment, the current guidelines focus on the symptomatic treatment of the affection. Our study aimed to evaluate the therapeutic advantages of the synergistic use of non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy in the treatment of knee osteoarthritis (KOA). PATIENTS, MATERIALS AND METHODS: The study comprised 46 individuals who were diagnosed with KOA and were admitted to the Department of Physical Medicine and Rehabilitation at the Emergency Clinical County Hospital of Craiova, Romania, between January 2021 and April 2022. All the participants received the same combination of pharmacological (Diclofenac 150 mg∕day, no more than 10 days∕month as needed) and non-pharmacological treatment (a 24-week plan of physical therapy). RESULTS: The patient group exhibited a statistically significant reduction in both the average Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index (p=0.0142) and the average Visual Analog Scale (VAS) (p=0.0023). Additionally, there was a statistically significant increase in both the average Knee Outcome Survey-Activities of Daily Living (KOS-ADL) (p=0.0128) and the average Oxford Knee Score (OKS) (p=0.0023). The study found a significant positive correlation between higher VAS ratings and cholesterol levels (p=0.0092), but no significant correlation between VAS scores and triglyceride levels (p=0.0986). Patients were evaluated for a further 24 weeks beyond the conclusion of the research to see if surgical intervention was necessary during this time. CONCLUSIONS: Our investigation tracked the WOMAC, VAS, KOS-ADL, and OKS measurements in a cohort of patients with KOA. The results demonstrate that the utilization of NSAIDs in conjunction with physical therapy effectively alleviates pain and enhances joint functionality.

THE IMPACT OF SYSTEMIC DRUGS ON DENTAL IMPLANT OSSEOINTEGRATION: A REVIEW.

The process of osteointegration of dental implants is a biological process. Systemic therapy can interfere with this process, affecting the growth and breakdown processes of the bone and ultimately leading to implant failure. This literature review focuses on specific groups of systemic drugs that directly impact osteointegration. The research in electronic literature was conducted using the National Library of Medicine's PubMed/MEDLINE database from March 2000 to February 2024. The following MeSH (Medical Subject Headings) terms were used: "implant osseointegration," "bisphosphonates," "non-steroidal anti-inflammatory drugs," "glucocorticoids," "proton pump inhibitors," and "selective serotonin reuptake inhibitors (SSRIs)." This search yielded 1,258 articles on implant osseointegration. Among these, 30 articles met our criteria for implant osseointegration and bisphosphonates, 2 articles for non-steroidal anti-inflammatory drugs (NSAIDs), 7 articles for glucocorticoids, 14 articles for proton pump inhibitors (PPIs), and 14 articles for selective serotonin reuptake inhibitors (SSRIs). Clinicians considering implant therapy should be mindful of potential medication-related implant failures. The present systematic review has identified an association between proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), glucocorticoids, and bisphosphonates with an increased implant failure rate.

Efficacy and safety of topical NSAIDs combined with physiotherapy for frozen shoulder: a randomized controlled trial.

OBJECTIVE: Frozen shoulder is a prevalent condition among individuals in their middle and later years. Invasive therapy has shown promising results in the treatment of frozen shoulders, but its widespread adoption has been hampered by high costs and the need for advanced medical technology. As a result, patients with frozen shoulders often turn to non-steroidal anti-inflammatory drugs (NSAIDs) for symptomatic relief. However, the oral administration of NSAIDs can lead to troublesome adverse effects on the gastrointestinal, cardiovascular, and urinary systems. In contrast, topical NSAIDs have gained attention for their excellent efficacy and lower adverse effects in various chronic pain conditions. Therefore, our study aimed to investigate the efficacy and safety of topical NSAIDs in improving pain and mobility among patients with frozen shoulders. PATIENTS AND METHODS: A total of 108 patients experiencing moderate to severe pain and mobility impairment due to frozen shoulder were enrolled in this study. The participants were randomly assigned to either the experimental group (n=72) or the control group (n=36). The experimental group received daily treatment with the loxoprofen hydrogel patch (LOX-P) in addition to basic rehabilitation physiotherapy. The control group was treated with flurbiprofen cataplasm (FLU-C) twice a day, along with rehabilitation physiotherapy. The primary endpoint for evaluating the efficacy of the two patches was the Constant-Murley score (CMS). Clinical symptom data, adverse events, and patient satisfaction were also recorded. RESULTS: After 14 days of treatment, the effective rate was 66.67% (n=48) in the experimental group and 41.67% (n=15) in the control group. The overall difference in the effective rates was 25.00% (95% CI=5.20-42.52; p=0.013). The safety profiles of the two topical agents were similar, with only a few adverse events reported. CONCLUSIONS: The loxoprofen hydrogel patch demonstrates a significant ability to alleviate shoulder pain and restore shoulder function in the treatment of frozen shoulder, with minimal adverse reactions. Chictr.org.cn ID: ChiCTR2100052375.

Factors associated with long-term clinical outcome in microscopic colitis.

BACKGROUND AND AIMS: Microscopic colitis has been increasingly recognized as a cause of chronic diarrhoea. We aimed to characterize the role of disease-related factors and treatments on the clinical outcomes of microscopic colitis. METHODS: We retrospectively reviewed the medical records of patients with microscopic colitis who were treated at the University of Chicago and Oregon Health & Science University between August 2010 and May 2016. Patient characteristics and treatments were evaluated as predictors of clinical outcomes using univariate and multivariate analyses. Clinical remission was defined as no symptoms associated with microscopic colitis based on physician assessment and histologic remission was defined as no evidence of histological inflammation of microscopic colitis. RESULTS: Seventy-two patients with microscopic colitis were included in the study (28 with lymphocytic colitis and 44 with collagenous colitis). Non-steroidal anti-inflammatory drugs, proton pump inhibitors and selective serotonin reuptake inhibitors were used in 23 (31.9%), 14 (19.4%) and 15 (20.8%), respectively, at the time of diagnosis. Among 46 patients with adequate follow-up data, 25 (54.3%) patients achieved clinical remission. Response to budesonide (p = .0002) and achieving histologic remission (p = .0008) were associated with clinical remission on univariate analysis. On multivariate analysis, budesonide response (p = .0052) was associated with clinical remission (odds ratio 25.00, 95% confidence interval 2.63-238.10). Among 22 patients who underwent a follow-up colonoscopy, five patients (22.7%) achieved histologic remission. All patients with histologic remission maintained clinical remission without medication, whereas only two patients (11.8%) were able to discontinue medical therapy when histologic inflammation was present (p = .0002). CONCLUSIONS: In the present cohort of patients with microscopic colitis, a favourable response to budesonide was significantly associated with long-term clinical remission, and all patients achieving histological remission were able to maintain clinical remission without further medical therapy. Larger studies are required to confirm these findings.

Exploring potential neuroimaging biomarkers for the response to non-steroidal anti-inflammatory drugs in episodic migraine.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability among individuals. Thus, this study aimed to explore a machine learning model based on the percentage of amplitude oscillations (PerAF) and gray matter volume (GMV) to predict the response to NSAIDs in migraine treatment. METHODS: Propensity score matching was adopted to match patients having migraine with response and nonresponse to NSAIDs, ensuring consistency in clinical characteristics and migraine-related features. Multimodal magnetic resonance imaging was employed to extract PerAF and GMV, followed by feature selection using the least absolute shrinkage and selection operator regression and recursive feature elimination algorithms. Multiple predictive models were constructed and the final model with the smallest predictive residuals was chosen. The model performance was evaluated using the area under the receiver operating characteristic (ROCAUC) curve, area under the precision-recall curve (PRAUC), balance accuracy (BACC), sensitivity, F1 score, positive predictive value (PPV), and negative predictive value (NPV). External validation was performed using a public database. Then, correlation analysis was performed between the neuroimaging predictors and clinical features in migraine. RESULTS: One hundred eighteen patients with migraine (59 responders and 59 non-responders) were enrolled. Six features (PerAF of left insula and left transverse temporal gyrus; and GMV of right superior frontal gyrus, left postcentral gyrus, right postcentral gyrus, and left precuneus) were observed. The random forest model with the lowest predictive residuals was selected and model metrics (ROCAUC, PRAUC, BACC, sensitivity, F1 score, PPV, and NPV) in the training and testing groups were 0.982, 0.983, 0.927, 0.976, 0.930, 0.889, and 0.973; and 0.711, 0.648, 0.639, 0.667,0.649, 0.632, and 0.647, respectively. The model metrics of external validation were 0.631, 0.651, 0.611, 0.808, 0.656, 0.553, and 0.706. Additionally, a significant positive correlation was found between the GMV of the left precuneus and attack time in non-responders. CONCLUSIONS: Our findings suggest the potential of multimodal neuroimaging features in predicting the efficacy of NSAIDs in migraine treatment and provide novel insights into the neural mechanisms underlying migraine and its optimized treatment strategy.

Continuous co-prescription of rebamipide prevents upper gastrointestinal bleeding in NSAID use for orthopaedic conditions: A nested case-control study using the LIFE Study database.

BACKGROUND: Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age. METHODS: A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan's Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category's odds ratio compared to non-users. FINDINGS: Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44-0.96) for Continuous-users and 2.57 (1.73-3.81) for Irregular-users. CONCLUSIONS: Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age.

Intravenous ibuprofen versus ketorolac for perioperative pain control in open abdominal hysterectomy: a randomized controlled trial.

BACKGROUND: We aimed to compare the analgesic effects of intravenous ibuprofen to ketorolac after open abdominal hysterectomy. METHODS: This randomized double-blinded controlled trial included adult women scheduled for elective open abdominal hysterectomy. Participants were randomized to receive either 30 mg ketorolac (n = 50) or 800 mg ibuprofen (n = 50) preoperatively, then every 8 h postoperatively for 24 h. All participants received paracetamol 1 gm/6 h. Rescue analgesic was given if the visual analogue scale (VAS) for pain assessment was > 3. The primary outcome was the mean postoperative dynamic VAS during the first 24 h. Secondary outcomes were static VAS, intraoperative fentanyl consumption, postoperative morphine consumption, time to independent movement, and patient's satisfaction. RESULTS: Forty-six patients in the ibuprofen group and fifty patients in the ketorolac group were analyzed. The 24-h dynamic and static VAS were similar in the two groups. The median (quartiles) dynamic VAS was 1.1 (0.9, 1.9) in the ibuprofen group versus 1.0 (0.7, 1.3) in the ketorolac group, P-value = 0.116; and the median (quartiles) static VAS was 0.9 (0.6, 1.3) in the ibuprofen group versus 0.7 (0.4, 1.1) in the ketorolac group, P-value = 0.113. The intra- and postoperative analgesic requirements were also similar in the two groups. However, patient satisfaction was slightly higher in the ketorolac group than that in the ibuprofen group (median [quartiles]: 6 [5, 7] versus 5 [4, 7], respectively), P-value: 0.009. CONCLUSION: The two drugs, intravenous ibuprofen and ketorolac produced similar analgesic profile in patients undergoing open abdominal hysterectomy receiving multimodal analgesic regimen. NCT05610384, Date of registration: 09/11/2022 CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05610384. https://clinicaltrials.gov/ct2/show/NCT05610384.

Aspirin as a chemopreventive agent for cutaneous melanoma: a literature review.

Rising melanoma rates have spurred interest in preventive strategies. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, show potential in reducing cancer risks. NSAIDs act on cyclooxygenase (COX) enzymes, impacting COX-2 associated with inflammation and cancer progression. This paper explores aspirin's role in cutaneous melanoma prevention, elucidating its mechanisms and acknowledging varying literature outcomes. Rather than providing conclusive recommendations, the review emphasizes the influence of individual factors, contributing to the ongoing dialogue on aspirin's complexities in melanoma prevention. A PubMed search using "Aspirin" AND "Cutaneous melanoma" yielded relevant English-language, peer-reviewed studies. Selection criteria focused exclusively on skin cancers, specifically cutaneous melanoma. Exclusions included studies covering various cancers, some non-dermatologic, and those not evaluating aspirin use independently but in conjunction with NSAIDs. The potential chemopreventive effects of aspirin and NSAIDs against melanoma have gained attention due to their association with a reduced risk of various cancers including gastric, colorectal, and breast. By inhibiting COX enzymes and the NF-κB pathway, these agents theoretically slow malignant cell activities, presenting a prospect for cancer prevention. Aspirin exhibits noteworthy effects, depleting growth-stimulating hormones, generating reactive oxygen species harmful to cancerous cells, and inhibiting COX-2 linked to cancer progression. Limited literature suggests survival benefits with aspirin use in stage II and III melanoma, possibly due to slowing disease progression, evident in smaller Breslow depths. Gender-specific responses to aspirin are notable, with some studies reporting a stronger chemopreventive correlation in females. It's crucial to note that geographic disparities, demographic cohorts, and individual-specific factors are confounding variables that may contribute to conflicting findings regarding aspirin's impact on melanoma. The association between aspirin use and melanoma risk is complex, with conflicting findings across diverse populations. Although it appears that more studies suggest a protective role for aspirin rather than not, evidence lacks consistency. Factors such as gender, geography, race, sun exposure, and health conditions play a role in shaping these varied outcomes, necessitating large-scale, prospective studies research and standardized parameters for more conclusive insights that may help guide tailored clinical strategies for melanoma prevention.

Pharmacologic interventions for primary glenohumeral osteoarthritis.

ABSTRACT: Primary glenohumeral osteoarthritis is a multifactorial condition with a complex cause that affects patients across different age groups, impairing physiologic and psychologic well-being, and substantially reducing patient quality of life and overall productivity. To effectively manage this condition, healthcare providers need to be well informed about treatment guidelines, as well as the available therapeutic options and the evidence supporting their use. Nonsurgical interventions should be regarded as the primary treatment option, particularly for patients in the initial phases of this condition. No conclusive guidelines exist for treating young and active patients, and the literature lacks high-quality data to evaluate the efficacy, safety, and long-term consequences of several interventions, regardless of patient characteristics and expectations.

[Current challenges for therapy of comorbid patients: a new look at celecoxib. A review].

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer's disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.

Comparison of grapiprant and meloxicam for management of postoperative joint pain in dogs: A randomized, double-blinded, prospective clinical trial.

BACKGROUND: Grapiprant is a novel anti-inflammatory drug approved for the treatment of pain associated with osteoarthritis in dogs. OBJECTIVE: Compare the efficacy of grapiprant vs meloxicam for the management of postoperative joint pain in dogs. ANIMALS: Forty-eight dogs presented with cranial cruciate ligament disease and treated by tibial plateau leveling osteotomy (TPLO) between May 2020 and May 2022. METHODS: In this randomized, double blinded, prospective clinical trial, client-owned dogs with naturally occurring unilateral cruciate ligament rupture were enrolled on the day of surgery. The day after surgery, all animals received a subcutaneous injection of 0.2 mg/kg of meloxicam and were randomly assigned to receive either oral grapiprant (2 mg/kg) or meloxicam (0.1 mg/kg), once a day for 14 days, in a blinded manner. The primary endpoint of the study was the pain severity (PSS) and interference (PIS) scores, assessed by the Canine Brief Pain Inventory (CBPI) at day 3, 7, 10 and 15 after the surgery. RESULTS: Three days after surgery, grapiprant treated dogs had lower PSS compared to meloxicam treated dogs with a mean ± SD of 2.76 ± 0.18 vs 3.25 ± 0.23, respectively (difference of -0.49 [95% CI -0.94 to -0.04], P = .032). Pain Interference Score was also lower in grapiprant group at day 3 (4.11 ± 0.18 vs 4.69 ± 0.16 in meloxicam group [difference of -0.58 {95% CI -1.03 to -0.13}, P = .013]) and at day 10 (2.23 ± 0.13 vs 2.72 ± 0.28 [difference of -0.49 {95% CI -0.92 to -0.01}, P = .049]). CONCLUSIONS AND CLINICAL IMPORTANCE: Our study supports the use of grapiprant as an alternative analgesic to meloxicam for management of postoperative joint pain in dogs.