Topical nonsteroidal anti-inflammatory drugs for management of pain syndrome

Chronic pain continues to remain one of the urgent problems of modern medicine. From 15 to 25% of the adult population suffers from chronic pain. Medical treatment includes the appointment of non-steroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants. The greatestform for the appointment of NSAIDs is the topical form. According to the recommendations of International and National societies for the treatment of pain syndrome, osteoarthritis (OA) therapy are recommended to start with topical NSAIDs, as drugs with less systemic adverse side effects (NSAIDs).Topical NSAIDs have proven analgesic and antiinflammatory efficacy in the treatment of diseases of the musculoskeletal system, musculoskeletal pain, but have a low risk of developing systemic NSAIDs in comparison with oral forms, which expands the possibilities of their appointment in patients with comorbid pathology (diseases of the gastrointestinal tract, cardiovascular risks).Among NSAIDs, diclofenac is the "gold standard" of analgesia. After topical application, diclofenac penetrates through the skin and further into the deeper underlying tissues while maintaining sufficient concentration to provide a therapeutic effect. The topical form of diclofenac – diclofenac diethylamine 2%, when used correctly, can cause an analgesic effect comparable to the oral form. This topical form has a high clinical efficacy in the treatment of acute musculoskeletal pain (sprains), the course of therapy takes 1 week, for chronic pain syndromes (knee OA or hand) the course of therapy is from 2 to less than 6 weeks. The clinical efficacy of diclofenac diethylamine monotherapy is comparable to that for complex therapy in combination with oral forms of NSAIDs, while having good tolerability.

Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

Objective To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. Design Systematic review and network meta-analysis of randomised trials. Data sources Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. Eligibility criteria for selecting studies Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. Outcomes and measures The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. Review methods Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. Results 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). Conclusions Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. Systematic review registration PROSPERO number CRD42020213656

Comparison of the Analgesic Effect of Nepafenac 0.1%, Ketorolac 0.5%, and Diclofenac 0.1% Ophthalmic Solution during Intravitreal Injection

Background: Pain during intravitreal injection (IVT) is inevitable and might reduce the patient’s compliance. Topical anesthetic eye drop usually is administered to reduce pain during IVT. However, severe ocular pain has been reported in some patients. The most effective anesthesia for IVT is still controversy. Objective: To evaluate the analgesic effect of three topical non-steroidal anti-inflammatory drugs (NSAIDs) eye drop, nepafenac 0.1%, ketorolac 0.5%, and diclofenac 0.1%, during IVT. Materials and Methods: The present study was a prospective randomized, double-blinded, placebo-controlled study. Patients undergoing intravitreal bevacizumab injections were randomly divided into four groups. Group 1, group 2, group 3, and group 4 received topical nepafenac 0.1%, topical ketorolac 0.5%, diclofenac 0.1%, and artificial tear (placebo), respectively. One hour after receiving the eye drops, all patients underwent IVT with topical anesthetic eye drop. Pain assessment was performed immediately after IVT using the Thai version of Short-Form McGill Pain Questionnaire (SF-MPQ). The SF-MPQ consists of the main component of the SF-MPQ, the visual analogue scale (VAS), and the present pain intensity (PPI). Results: Eighty patients voluntarily enrolled in the present study. Median of VAS scores were 1.5 (0.8 to 4.6), 2.3 (1.5 to 4.6), 1.5 (1 to 3.2), and 2.4 (1.4 to 3.6) in nepafenac group, ketorolac group, diclofenac group, and placebo group, respectively (p=0.159). Median of the main component of the SF-MPQ scores were 4 (1.25 to 5.75), 5 (2.25 to 11.5), 5 (1.25 to 9.5), and 5 (3 to 13), in nepafenac group, ketorolac group, diclofenac group and placebo group, respectively (p=0.409). Median of the PPI scores were 1 (1 to 1.75), 1 (1 to 2), 1 (1 to 1), and 1 (1 to 2), in nepafenac group, ketorolac group, diclofenac group, and placebo group, respectively (p=0.529). Conclusion: There were no significant differences in analgesic effect during IVT between topical NSAIDs, nepafenac 0.1%, ketorolac 0.5%, diclofenac 0.1%, and placebo. Keywords: Intravitreal injection; Analgesic effect; Topical NSAIDs eye drop; SF-MPQ

A Systematic Review and Meta-Analysis of the Efficacy of Evening Primrose Oil for Mastalgia Treatment

Mastalgia, or breast pain, is common among women which can lead to significant impairment in daily living. Hence, finding an effective treatment that can alleviate the symptom is very important. Thus, we carry out this study to determine the efficacy of evening primrose oil (EPO) for mastalgia treatment in women. The review included published randomised clinical trials that evaluated EPO used for treating mastalgia against a placebo or other treatments, irrespective of the blinding procedure, publication status, or sample size. Two independent authors screened the titles and abstracts of the identified trials; full texts of relevant trials were evaluated for eligibility. Two reviewers independently extracted data on the methods, interventions, outcomes, and risk of bias. The random-effects model was used for estimating the risk ratios and mean differences with 95% confidence intervals. Thirteen trials with 1752 randomised patients were included. The results showed that EPO has no difference to reduce breast pain compared to topical NSAIDS, danazol, or vitamin E. The number of patients who achieved pain relief was no different compared to the placebo or other treatments. The EPO does not increase adverse events, such as nausea, abdominal bloating, headache or giddiness, increase weight gain, and altered taste compared to a placebo or other treatments. EPO is a safe medication with similar efficacy for pain control in women with mastalgia compared to a placebo, topical NSAIDS, danazol, or vitamin E.

POS1324 TREATMENT OF UVEITIS ASSOCIATED WITH JUVENILE IDIOPATHIC ARTHRITIS: A SEVEN YEARS’ SINGLE-CENTRE EXPERIENCE

Background:Uveitis (U) is one of the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA). It is usually revealed in 10-20% of children with JIA, often asymptomatic and sometimes the onset of U precedes the onset of arthritis. Being inappropriately treated, U leads to vision loss in up to 20% of children. Despite the efforts of the Standardization of Uveitis Nomenclature (SUN) Working Group and the European initiative Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) which optimized management of JIA-associated U [1], the actual treatment is mostly based on physicians’ experience. Initial treatment typically includes topical glucocorticoids (G) or systemic immunosuppressive therapy if topical G don’t work. Methotrexate (MTX) is the first-line systemic immunosuppressive agent, followed by tumor necrosis factor inhibitors (TNFi) [1,2].Objectives:To provide treatment recommendations for JIA-associated U based on monitoring of 221 patients during 7 years.Methods:Data collected during 2240 hospitalisations of 221 patients aged 3 - 17 years treated at the State Pediatric Medical University in years 2014 - 2020 were analyzed. U and JIA were diagnosed according to the SUN and ACR recommendations. Initial treatment of U included topical G or non-steroidal anti-inflammatory drugs (NSAIDs). Treatment of JIA included systemic NSAIDs, cytostatics (MTX, Cyclosporine or Cyclophosphamide) and biologics: Adalimumab (Ada), Infliximab (Inf), Etanercept (Eta), Abatacept (Aba), Tocilizumab (Toc), Golimumab (Gol). Statistical analysis included traditional Descriptive Statistics, Spearman Rank Order Correlation (SROC) and Multivariate Exploratory Techniques [Statistica for Windows, Statsoft].Results:Of all patients with JIA-associated U the proportion of those treated with biologics during the monitoring increased from 60 to 70% (of them, Ada 79 - 93%, Inf 7 - 1%, Eta 5 - 1%, Aba 7 - 3%, Toc 7 - 0%, Gol 0 - 3%). Of all children in whom U was diagnosed later than arthritis 36% were treated with systemic NSAIDs, 25% - with cytostatics (MTX - 84%, Cyclosporine - 8%, Cyclophosphamide - 8%), 23% - with systemic G, 6% - with biologics (Eta - 83%, Toc - 17%). Of patients in whom U and arthritis were diagnosed simultaneously, 95% were treated with cytostatics (MTX - 95%, Cyclosporine - 15%), 93% - with topical G, 91% - with topical NSAIDs, 81% - with systemic G, 60% - with systemic NSAIDs. Efficacy of treatment in terms of SROK showed evidence of steady improvement already after 1 month of therapy with TNFi or with MTX (increase of r during the first year from 0.37 to 0,62, p<0.02; from 0.37 to 0.55, p<0.05 respectively), though r was never higher than 0.84 during the first 3 years of treatment. Topical NSAIDs and G were less effective: improvement was revealed after 3 months of treatment, it was not so steady and r was never higher than 0.35. Systemic NSAID’s were not effective at all.Conclusion:1. The likelihood of improvement of U treated with TNFi (Eta excepted) after one month, after 1 and after 3 years of therapy was 37%, 62% and 84% respectively. For MTX this likelihood was 37% after 1 month and 55% after 3 months.2. TNFi (Eta excepted) in treatment of JIA prevents the onset of U, thereby supposing its early administration.3. Eta neither prevents nor treats U.4. Topical NSAIDs and G can hardly be recommended as a reliable means for treatment of U without TNFi and MTX.5. Systemic NSAIDs neither prevent nor treat JIA-associated U.References:[1]Constantin T, Foeldvari I, Anton J, et al. Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative Ann Rheum Dis 2018;77:1107–1117[2]Angeles-Han ST, Ringold S, Beukelman T, Lovell D et al., 2018 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis. Arthritis Care Res (Hoboken). 2019 June; 71(6): 703–716Disclosure of Interests:None declared

AB0593 PERCEPTION OF THE EFFECTIVENESS OF TOPICAL ANALGESICS IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE

Background:Osteoarthritis of the knee is one of the most common joint diseases. It mainly manifests as pain and can become disabling over time. Several symptomatic therapeutic methods are used to relieve patients with knee osteoarthritis and give them more autonomy. Topical analgesics are considered as an interesting alternative for old and poly-medicated patients.Objectives:The aim of this work was to assess the perception of the effectiveness of topical analgesics by patients followed for knee osteoarthritis.Methods:A prospective study has been conducted collecting 66 patients followed for knee osteoarthritis at different stages of the disease and under topical analgesic treatment. Epidemiological data, physical examination and x-ray data were collected. The impact of knee osteoarthritis was evaluated by the Lequesne and WOMAC indices. Patients were asked to evaluate their perception about: the time that makes the medication to act, the duration of action and overall satisfaction with the topical analgesic by rating it from 0 to 5. Zero represents complete dissatisfaction while 5 represents complete satisfaction. Patients were also asked about the side effects observed after the use of the topical treatment and whether they recommended this treatment to a friend or a parent.Results:In the studied population, the majority of patients were women (87%) with an average age of 55 years. The most common comorbidities were high blood pressure (61%), diabetes (38%) and osteoporosis (36%). Sixty-nine percent of patients were taking more than two oral treatments. The average duration of development of osteoarthritis of the knee was 9 years. The most common radiological stage was stage 1 (58%). The site was femorotibial in 88% of cases, patellofemoral in 4% of cases and bi or tri compartmental in 8% of cases. The osteoarthritis most often affected both knees in 86% of cases.The average of the Lequesne index was 11. The average WOMAC index was 12 for pain, 1.5 for stiffness and 48 for dysfunction.All the patients surveyed were on topical non-steroidal anti-inflammatory drugs (NSAIDs), 37.7% combined local herbal medicine with local NSAIDs, 53% were taking oral analgesics, and 19% were using oral non-steroidal anti-inflammatory drugs in the past month.The average rating for time that takes the topical treatment to act was 2.9, for duration of action was 1.2, and for overall satisfaction was 2.8. No adverse effects of topical treatment have been reported.For patients over 60 years old, better satisfaction was noted (the average score for overall satisfaction was 3.2).Patients with a WOMAC Pain Index greater than 10 were less satisfied (the average overall satisfaction score was 1.1). Patients who took both topical NSAIDs and topical herbal medicine reported that topical NSAIDs were more effective in 66% of cases. Forty percent of patients recommended topical treatment to a friend or a family member.Conclusion:In patients with chronic pain associated to osteoarthritis of the knee, topical analgesics are considered a good long-term therapeutic alternative. Patients are generally satisfied with the effectiveness of the local treatment, in particular the immediate effect felt after application, but less satisfied with the duration of action. Perception of effectiveness appears to be affected by age and degree of pain.References:[1]D. Y. Wall, “Topical Nonsteroidal Anti-Inflammatory Drugs for Chronic Musculoskeletal Pain in Adults,” p. 3, 2017.[2]R. L. Barkin, “The Pharmacology of Topical Analgesics,” null, vol. 125, no. sup1, pp. 7–18, Jul. 2013, doi: 10.1080/00325481.2013.1110566911.Disclosure of Interests:None declared.