Philip Courtney

Key questions concerning paracetamol and NSAIDs for osteoarthritis

Paracetamol has a pivotal role in the pharmacological treatment of symptomatic OA Expert guidelines from both sides of the Atlantic have consistently recommended paracetamol, not non-steroidal anti-inflammatory drugs (NSAIDs), as the initial oral drug treatment for osteoarthritis (OA).1–5 This has been justified by the excellent safety record and low cost of paracetamol relative to NSAIDs, and the absence of any significant clinical benefit of NSAIDs over simple analgesia. However, recent data from the USA suggest that NSAIDs may be better than paracetamol for symptom relief in large joint (hip, knee) OA.6–8 These data follow shortly after an unprecedentedly high profile launch and promotion of selective inhibitors of cyclo-oxygenase 2 (coxibs). The clinical benefit of coxibs in OA is equivalent to that of traditional NSAIDs, but coxibs do not have the increased risk of severe gastrointestinal (GI) side effects (peptic ulceration, bleeding, perforation, and obstruction). In America, particularly, these events have led to an intense debate about the relative role of NSAIDs, coxibs, and paracetamol in OA management. This review deals with key questions relating to such drug prescribing for the management of OA. Although guidelines and reviews about the management of OA seem to be obsessed with this question, it probably has little relevance to clinical practice. Many patients treat themselves before consulting any doctor and have tried over the counter medicines that may include both paracetamol and NSAIDs.8 The concept of which drug to use first implies that monotherapy is the norm. However, most clinical trials of NSAIDs and coxibs allow concomitant paracetamol as “escape analgesia” and in a clinical setting a package of care is usually delivered. As rheumatologists largely see patients with OA only once and after a considerable delay, a more pertinent question for them may be “which drug, or drugs, …

Synovial pathology detected on ultrasound correlates with the severity of radiographic knee osteoarthritis more than with symptoms

Summary Objective To [1] compare the frequency and severity of ultrasound (US) features in people with normal knees (controls), knee pain (KP), asymptomatic radiographic OA (ROA), and symptomatic OA (SROA), [2] examine relationships between US features, pain and radiographic severity, [3] explore the relationship between change in pain and US features over a 3-month period. Method Community participants were recruited into a multiple group case–control study. All underwent assessment for pain, knee radiographs and US examination for effusion, synovial hypertrophy, popliteal cysts and power Doppler (PD) signal within the synovium. A 3-month follow-up was undertaken in over half of control and SROA participants. Results 243 participants were recruited (90 controls; 59 KP; 32 ROA; 62 SROA). Effusion and synovial hypertrophy were more common in ROA and SROA participants. Severity of effusion and synovial hypertrophy were greater in SROA compared to ROA (P < 0.05). Severity of US effusion and synovial hypertrophy were correlated with radiographic severity (r = 0.6 and r = 0.7, P < 0.01) but the relationship between pain severity and US features was weak (r = 0.3, P < 0.01). In SROA participants, pain severity did not change in tandem with a change in synovial hypertrophy over time. Conclusion US abnormalities are common in OA. Effusion and synovial hypertrophy were moderately correlated with radiographic severity but the relationship with pain is less strong. The degree to which these features reflect “active inflammation” is questionable and they may be better considered as part of the total organ pathology in OA. Further studies are warranted to confirm these findings.

Ultrasound detected synovial change and pain response following intra-articular injection of corticosteroid and a placebo in symptomatic osteoarthritic knees: a pilot study

Intra-articular injection (IAI) of steroid is a safe and effective treatment for painful knee osteoarthritis (OA).1 The mechanism of action is thought to be partly mediated by an anti-inflammatory effect on the synovium which may be detected by changes observed on ultrasound (US) examination.2 Placebo IAI of saline can also significantly reduce pain though the mechanisms are not generally thought to associate with a peripheral effect.3–5 This pilot study aimed to investigate whether improved knee pain correlated with improved US measures following IAI of a corticosteroid or a placebo in OA knees. Twenty-five participants with painful knee OA (Kellgren and Lawrence grade ≥2) were randomised to one of two treatment sequences (IAI of methylprednisolone (40 mg in 1 mL) followed by IAI of saline placebo (1 mL, 0.9%), or vice versa) to their most painful knee. Synovial fluid equal to volume injected …

Brief Report: Monosodium Urate Monohydrate Crystal Deposits Are Common in Asymptomatic Sons of Patients With Gout: The Sons of Gout Study

To estimate the prevalence and distribution of asymptomatic monosodium urate monohydrate (MSU) crystal deposition in sons of patients with gout.

FRI0499 Retrospective CASE Series of Refractory Antisynthetase Syndrome Successfully Treated with Rituximab (3 CASES)

Background Antisynthetase syndrome (ASS) is an idiopathic inflammatory myopathy characterised by the presence of anti-Jo-1 antibodies. Patients usually present with myositis, interstitial lung diseases, and arthritis. Corticosteroid therapy is the first line treatment. With regard to immunosuppressive use, no consensus has been reached. Rituximab has been reported to be successful in treatment of refractory ASS in small case series Objectives We report our experience of using rituximab in refractory ASS by describing the outcome and follow up of 3 cases Methods The case notes of 3 patients (2 males and 1 female; ages: 50, 42, and 54 years), diagnosed with ASS based on positive anti-Jo1 antibodies and muscle biopsy, were analyzed retrospectively. Treatment with several conventional therapeutic agents was tried sequentially over a mean period of 10 months without sustained remission (see Figs. 1, 2 and 3). In view of the refractory nature of their disease, a decision to commence rituximab was made (1000 mg IV, twice, with a 2-week interval). The available follow up periods for the 3 patients are 36 months in 2 patients, and 67 months in 1 patient. Response to treatment was assessed by improvement in muscle weakness & creatinine kinase (CK) levels Results Response to treatment was observed after a period of 4-5 months following treatment with rituximab. This manifested as improvement in symptoms (muscle weakness, joint pain and shortness of breath), & CK levels (see Figs. 1, 2, and 3). In the first patient (Fig. 1) the improvement following the initial treatment with rituximab was sustained for almost 3 years before he required retreatment with rituximab for relapses (relapsed 4 times afterwards over a period of 32 months, with an average of 11 months between relapses). Retreatment with rituximab in the second patient (Fig. 2) who relapsed at 8 and 18 months following the initial treatment resulted in remission 4-5 months later, and eventually he came off immunosupressive therapy. Retreatment with rituximab in the third patient (Fig. 3) who relapsed at 9 months following initial treatment resulted in remission 4-5 months later. She remained well and continued to receive rituximab prophylactically 6-monthly. The 3 patients have been successfully weaned off the higher dose of prednisolone they used to be on prior to treatment with rituximab; the first patient is currently maintained on prednisolone alone (10 mg daily); the second patient was weaned off prednisolone successfully and is currently on no treatment; while the third is maintained on prednisolone 5 mg daily plus methotrexate 25 mg weekly Conclusions This small retrospective case series indicates a beneficial effect of rituximab in ASS refractory to conventional treatment, in keeping with other case series1,2. However the response to treatment may take several months. The relapses at an average of 10 months following initial treatment with rituximab coincide with the timing of repopulation. The optimal timing of retreatment and whether prophylactic retreatment with rituximab at time of repopulation should be considered, remain to be defined. References Martha Sem et al. Rituximab treatment of the anti-synthetase syndrome - a retrospective case series. Rheumatology (2009) 48 (8): 968-971. Elien A. M. Mahler et al. Rituximab treatment in patients with refractory inflammatory myopathies. Rheumatology (2011) doi: 10.1093/rheumatology/ker088 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1878

OP0315 Ultrasound Features of Inflammation in the Knee Joint and its Relationship to Pain and Radiographic Osteoarthritis

Background Ultrasound (US) is a useful imaging modality that allows the evaluation of features suggestive of inflammation in osteoarthritis (OA). US features are more common in those with painful knee OA but the association between them remains inconclusive. Objectives To determine: [1] whether the frequency of ultrasound (US) features of inflammation differs between people with (a) normal asymptomatic knees (controls); (b) knee pain (KP) with no radiographic osteoarthritis (ROA); (c) asymptomatic ROA; and (d) symptomatic ROA (SROA); [2] whether US features associate with knee pain, OA change on x-ray, or symptoms and signs of inflammation; and [3] whether US features change in parallel with temporal change in knee pain. Methods A multiple group case-control study design was used. Community participants were recruited and divided into 4 groups based on presence or absence of (1) knee pain and (2) ROA. Standardised knee radiographs and assessments for pain, stiffness and function were carried out. All underwent US examination for effusion, synovial hypertrophy, popliteal cysts and power Doppler signal (PD) within the synovium. Features were dichotomised as present/absent, and grey-scale features were measured directly in mm. Follow-up US and pain assessments were collected in some OA and non-OA participants after 3 months. Comparisons between groups were examined using Χ2 tests, one-way ANOVA and post-hoc Bonferroni tests. Logistic regression was used to examine association between US features, knee pain and ROA adjusting for age, sex and BMI. Results 243 participants were recruited: 90 controls, 59 with KP, 32 with ROA and 62 with SROA. Greyscale US features of inflammation were more common in SROA (effusion 92%, synovial hypertrophy 82% and popliteal cysts 39%) than control and KP participants (p<0.05). US effusion, synovial hypertrophy and popliteal cysts were strongly associated with ROA (aOR(95%CI) =13.39 (6.14, 29.02); 14.39 (6.28, 32.94); 3.19 (1.42, 7.17) respectively) but only synovial hypertrophy was independently associated with pain (aOR=6.56 (2.85, 15.11)). No independent associations were found between PD signal, and pain or ROA. Follow-up of 65 non-OA and 51 OA participants found no relationship between change in pain severity and change in US features. Conclusions US features of inflammation are most strongly associated with ROA but the relationship with symptoms is less clear. This supports synovial changes as predominantly a secondary rather than primary feature of OA. Further studies are warranted to confirm these findings. Acknowledgements We are grateful to Arthritis Research UK for funding this work (AHP Training Fellowship Grant no.18861). Disclosure of Interest None Declared