Comparison of the effect of marine-derived omega-3 fatty acids (n-3 FAs) as an adjunct to a non-steroidal inflammatory drug (NSAID) therapy vs NSAID therapy alone, for dogs with osteoarthritis

PICO question Does treatment with a non-steroidal anti-inflammatory drug (NSAID) with supplementation of marine-derived omega-3 fatty acids (n-3FAs) compared to the NSAID alone, result in an increased ability to exert force by the osteoarthritic limb(s) of dogs or alleviate other measures of osteoarthritis? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed Two prospective, block-randomised, clinical trials Strength of evidence None Outcomes reported Kwananocha et al. (2016) investigated administration of carprofen supplemented with marine-derived n-3 FAs, to carprofen alone, administered over 4 weeks. Vijarnsorn et al. (2019) investigated administration of firocoxib supplemented with n-3FA, to firocoxib alone, for 4 weeks. There were no statistical differences between treatment groups at week 2 and week 4 post-treatment for either study. Both studies also reported orthopaedic assessment score (OAS) based on scoring the extent of patient lameness and pain in the affected joint. There were no statistical changes in OASs between treatment groups at week 2 or week 4 post-treatment for either study Conclusion There is no evidence that marine-derived n-3 FAs provide additional benefit when used as adjunctive agents with NSAIDs for the treatment of canine osteoarthritis How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Efficacy of Chondroitin Sulfate in Patients with Knee and Hip Osteoarthritis

Currently chondroitin sulfate (CS) is the most studied drug from the group of «chondroprotectors». The article shows the role of CS in the treatment of osteoarthritis (OA): mechanism of action, clinical efficacy and safety in patients with OA with comorbidity. Evidence for the effectiveness and safety of the use of CS has been analyzed. The place of this drug in Russian and international clinical guidelines for the management of patients with OA is discussed.In domestic practice, the parenteral form of CS is often used in patients with OA. The parenteral form of CS for intramuscular and intra-articular administration (Chondroguard®) has a number of advantages, including the rapid onset of the effect. This enables reducing the dose in a short time or completely abandon the use of non-steroidal anti-inflammatory drugs (NSAIDs), which is extremely important for patients with OA with comorbidity. Chondroguard® can be recommended for initial use in exacerbations of chronic joint and back pain in OA, including in patients with relative and absolute contraindications for NSAID therapy.

Gastroprotection during long-term NSAID use – what we know after 120 years of observations?

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed classes of medications. The broad spectrum of side effects following long-term NSAID therapy includes mainly, but not only, gastrointestinal complications. Risk stratification of the gastrointestinal complications events is an important element of planning NSAIDs therapy, which allows to determine the indications for the use of proton pump inhibitors. This article presents the criteria for assessment and the method of adequate prevention of gastrointestinal side effects in patients receiving long-term NSAID therapy.

AB0474 THE USE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) IN WOMEN WITH ANKYLOSING SPONDYLITIS (AS) DURING PREGNANCY

Background:NSAIDs remain the first-line drugs in treatment of AS. During pregnancy, COX-2 non-selective NSAIDs are allowed for intake up to 32 weeks, but the question of the dose-dependent effect of NSAIDs on fetal organogenesis in the 1st trimester and on fetal kidney function and the increased risk of bleeding in childbirth when taken in the second half of pregnancy continues to be discussed. At the same time, data on the effectiveness of NSAIDs, including their low and medium doses, during pregnancy are extremely small.Objectives:to describe the frequency of using NSAIDs during pregnancy, to determine relationship between the dose of NSAIDs, adherence to therapy with the activity of AS.Methods:50 pregnancies were followed in 49 pregnant women with confirmed AS (modified New York criteria, 1984). The average age of the pts was 31.6 ± 4.9 years, the duration of the disease was 134.4 ± 85.8 months. The visits were conducted at 10-11, 20-21, and 31-32 weeks of pregnancy. The BASDAI in the month of conception and in the trimesters (trim.) of pregnancy was: 1,4[0,6; 3,3]; 2,3[1,2; 4,4]; 2,8[1,4; 4,2] and 2,2[1,6; 4,0], respectively. The level of nocturnal back pain according to the NRS in the first, second and third trim. was: 3.2±2.0; 5.4±2.5 and 5.2±2.6, respectively. The drug of choice was ibuprofen at a maximum daily dose of 1200 mg, its withdrawal - no later than 32 weeks of pregnancy.Adherence to NSAID therapy was defined as the ratio of the actual dose taken to the prescribed dose; an indicator of less than 80% was regarded as non-adherence to therapy. The total dose of NSAIDs was determined by the NSAID intake index (M. Dougados, 2001). The” actual daily dose” of ibuprofen was the sum of the doses of ibuprofen taken, divided by the number of actual days of taking the drug. The “average daily dose” was defined as the sum of the ibuprofen doses taken, divided by the number of days in the trimester.Results:At the time of conception and in the first, second and third trim. of pregnancy, NSAIDs were taken 23 (46%), 20 (40%), 30 (60%) and 21 (43.8%) women, respectively. The NSAID intake index, the actual and average daily dose of ibuprofen are shown in the Table 1.month of conceptiontrim. 1trim. 2trim. 3the actual daily dose, mg-700[425; 800]800[400; 1000]750[400; 1200]the average daily dose, mg-158[87,9; 307,7]355,1[138,5; 685,7]580[320; 1200]NSAIDs intake index28,6 [16,7; 50]5,8 [2,9; 11,8]15,5 [4,7; 30,9]24,4 [9,5; 50]The index of NSAID intake in the first trim. was lower than before pregnancy and in the second half of gestation (p<0.05 compared to the month of conception, II and III trim.). The average daily dose of ibuprofen was also lower in the first trim. than in the second and third trim. (p<0.05), while the actual daily dose in the second trim. was higher than in the first and third trim. (p<0.05 in all cases).There was no correlation between BASDAI AS activity, the level of nocturnal pain and the ibuprofen intake index, likewise the fact of NSAID withdrawal throughout pregnancy. In addition, there were no differences in BASDAI levels and back pain in women with a subjective need for NSAIDs, who did and did’t take ibuprofen.50% of women were committed to NSAID therapy in the first trim., 43.5% in the second trim., and 67.4% in the third trim. In pts with non-adherence to NSAID therapy, the BASDAI level was higher than in those who followed the recommendations of the rheumatologist throughout pregnancy: in the first trim. – 3.8[3.4; 4.7] and 1.7[0.8; 2.2]; in the second trim. - 3[2.3; 4.6] and 1.4[0.8; 2.7]; in the third trim. - 3.1[2.1; 4.0] and 1.7[1.1; 4.0], p<0.05 in all cases. However, women with adherence > 80% were initially less active and NSAIDs were prescribed “on demand”, which increased their compliance.Conclusion:intake of ibuprofen in low doses does not affect the activity of AS. Due to the ongoing discussion about the effect of NSAIDs on neonatal outcomes, further international studies are required for development an optimal treatment regimen during pregnancy with a possible extension of the indications for the appointment of TNF inhibitors (BASDAI<4).Disclosure of Interests:None declared.

AB0573 DUPILUMAB-INDUCED ENTHESITIS/ARTHRITIS IN PATIENTS WITH ATOPIC DERMATITIS: A RETROSPECTIVE OBSERVATIONAL STUDY

Background:Atopic dermatitis (AD) is a common skin condition with a prevalence of 2–10% in adults1. IL-4 and IL-13 play a key role in the pathogenesis. Dupilumab, a human IgG4 monoclonal antibody binding the alpha subunit of the IL-4 receptor, blocking IL-4 and IL-13 signaling, has important efficacy in this difficult to treat disease. We first reported a musculoskeletal (MSK) adverse effect of enthesis/arthritis developing in 3 patients in 20192.Objectives:To report the ongoing experience at our centre of this new clinical paradigm, incidence and patient progress including clinical presentation, imaging and management.Methods:Clinical and radiological data was collected from electronic case records of all cases presenting with features of enthesitis/arthritis between October 2018 and January 2021.Results:Since initiation of dupilumab at GSTT, approximately 400 adults with moderate-to-severe AD have received at least one dose. Of these, 23 patients (14 men, 9 women) had the clinical syndrome of inflammatory enthesitis/tenosynovitis/arthritis. Nine patients had both enthesitis and arthritis, 10 enthesitis, 3 enthesitis and tenosynovitis and 1 arthritis only. Four of these also reported new onset inflammatory back pain symptoms. None had a preceding history of arthritis or enthesitis. Median onset of symptoms following initiation of dupilumab was 4 months. However, onset of symptoms ranged between 2 weeks and 48 months. Imaging (US/MRI) was performed in 18 patients, 11 with Doppler US positive enthesitis confirming clinical findings. Most common sites were lateral epicondyles, achilles and patella tendons. Two patients with more disabling symptoms had MRI confirmed gluteus medius and hamstring enthesitis and arthritis. Spine and SI joint MRI in 4 patients was negative. Most patients had normal inflammatory markers except 2; CRP 117, ESR 96 and CRP 13, ESR 10. All patients had very good AD response to dupilumab, average EASI score before and after Dupilumab was 21 and 4.2 respectively. One patient developed skin manifestations of guttate psoriasis, with subsequent disabling arthritis/enthesitis. Due to the life-changing beneficial effect of dupilumab therapy most patients did not want to stop therapy. We used NSAID therapy, etoricoxib/celecoxib/naproxen for symptom relief which was usually partly effective allowing continuation of dupilumab treatment in most. Five patients with severe MSK symptoms stopped Dupilumab completely. Some patients temporarily paused therapy but re-started as their AD became worse, often changing from the usual 2 weekly to 4 weekly dosing. Most patients continuing dupilumab had persistent MSK symptoms. Four patients who stopped dupilumab were treated with baricitinib, which has potential efficacy for both MSK symptoms and AD. Two did not tolerate it and remained on NSAID therapy.Conclusion:These data further characterize a new syndrome of enthesitis and/or arthritis induced by Dupilumab. In those with mild MSK symptoms use of NSAIDs allows continuation of full-dose dupilumab, in moderate cases reducing dupilumab dose frequency plus NSAID therapy maintains function. Most patients had on-going MSK symptoms. In more severe cases JAKi therapy may be an effective strategy. Our initial hypothesis that inhibition of IL-4/13 by dupilumab triggers an IL-17/23/TNF-mediated inflammatory MSK syndrome in some patients is supported by a recent in vitro study3.References:[1]Beck L et al. Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis. July 10, 2014. N Engl J Med 2014; 371:130-139[2]Willsmore ZN et al. Development of inflammatory arthritis and enthesitis in patients on dupilumab: a case series. Br J Dermatol 2019; 0. doi:10.1111/bjd.18031.[3]Bridegwood C et al. Regulation of entheseal IL-23 expression by IL-4 and IL-13 as an explanation for arthropathy development under dupilumab therapy. Rheumatology (Oxford). 2020 Nov 30:keaa568. doi: 10.1093/rheumatology/keaa568Disclosure of Interests:Joseph Nathan: None declared., Catherine Hughes Speakers bureau: Presented for Abbvie, Samir Patel: None declared., Libin Mathew: None declared., Catherine Smith Grant/research support from: Grants/research support; Professor Smith is a PI/CoPI on a number of commercially supported studie (Abbvie, Janssen, Leo, Sanofi)., Andrew Pink Paid instructor for: Speaker or advisor to Lilly, Abbvie, Sanofi, Leo, Almirall, Novartis, Janssen, UCB, Galderma, BMS, La-Roche Posay, Richard Woolf: None declared., Bina Menon Speakers bureau: Presented for Abbvie, L Bruce Kirkham Grant/research support from: Professor Kirkham has received honoraria and/or research funding from AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB.

Problems of prescribing nonsteroidal anti-inflammatory drugs for reproductive-aged women with ankylosing spondylitis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medications for ankylosing spondylitis (AS); their action is associated with blockade of the enzyme cyclooxygenase 2 and with a mediated decrease in the synthesis of prostaglandins (PGs). However, PGs play an important role in regulating the functions of the female reproductive system. The paper presents an update on the participation of PG in folliculogenesis, ovulation, implantation, and development of the embryo, and labor activity. Based on experimental and clinical findings, the authors discuss whether due to inhibition of the synthesis of PGs, NSAIDs are able to cause ovulation failure, including luteinized unovulated follicle syndrome and spontaneous abortions. Further investigation is justified to determine the most optimal NSAID therapy regimens when planning pregnancy and during gestation in women with AS.