OMERACT Filter 2.1: Elaboration of the Conceptual Framework for Outcome Measurement in Health Intervention Studies

Objective: The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 framework was developed in 2014 to aid core outcome set development by describing the full universe of “measurable aspects of health conditions” from which core domains can be selected. This paper provides elaborations and updated concepts (OMERACT Filter 2.1). Methods: At OMERACT 2018, we discussed challenges in the framework application caused by unclear or ambiguous wording and terms and incompletely developed concepts. Results: The updated OMERACT Filter 2.1 framework makes benefits and harms explicit, clarifies concepts, and improves naming of various terms. Conclusion: We expect that the Filter 2.1 framework will improve the process of core set development

Longitudinal Numbers-Needed-To-Treat (NNT) for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis

<p>Abstract</p> <p>Background</p> <p>Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs.</p> <p>Methods</p> <p>This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation.</p> <p>Results</p> <p>For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks.</p> <p>Conclusions</p> <p>For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of NNTs and responder analyses provide additional, complementary information beyond population mean responses when assessing efficacy compared to placebo and amongst active therapies.</p

Safety and effectiveness responses to etanercept for rheumatoid arthritis in Japan: a sub-analysis of a post-marketing surveillance study focusing on the duration of rheumatoid arthritis

The aim is to investigate the relationship of duration of rheumatoid arthritis (RA) with safety and effectiveness of etanercept (ETN) in Japan. Post-marketing surveillance data for 7,099 patients treated with ETN were analyzed. Baseline characteristics, treatment effectiveness, incidence of adverse events (AEs), and serious AEs (SAEs) in relation to duration of RA were studied. At baseline, patients with RA for longer duration were older, weighed less, had more comorbidities, allergies, and corticosteroid use, but smoked less and had less morning stiffness. By 2–5 years with RA, more than half of the patients had advanced to Steinbrocker radiographic stage III or IV. Methotrexate (MTX) was the most commonly used pre-treatment disease-modifying antirheumatic drug; however, concomitant MTX use and its dose were lower among patients with longer duration of RA. Remission rates (26.6%) were greatest among patients having RA for <2 years. Less AEs and SAEs were observed among patients with shorter duration of RA. These results suggest that RA treatment in Japan in the era pre-biologics may not have been adequate to control disease activity and prevent joint destruction. Patients with shorter duration of RA may have better physical status which allows the opportunity to treat more intensively putting a higher percentage of patients in remission and possibly decreasing exposure to SAEs

A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a diverse class of drugs and are among the most commonly used analgesics for arthritic pain worldwide, though long-term use is associated with a spectrum of adverse effects. The introduction of cyclooxygenase-2-selective NSAIDs early in the last decade offered an alternative to traditional NSAIDs with similar efficacy and improved gastrointestinal tolerability; however, emerging concerns about cardiovascular safety resulted in the withdrawal of two agents (rofecoxib and valdecoxib) in the mid-2000s and, subsequently, in an overall reduction in NSAID use. It is now understood that all NSAIDs are associated with some varying degree of gastrointestinal and cardiovascular risk. Guidelines still recommend their use, but little is known of how patients use these agents. While strategies and guidelines aimed at reducing NSAID-associated complications exist, there is a need for evidence-based algorithms combining cardiovascular and gastrointestinal factors that can be used to aid treatment decisions at an individual patient level

Ultrasound assessment of response to intra-articular therapy in osteoarthritis of the knee

Objective. Assessment of the synovium in patients with knee OA is of great potential value for clinical trials. Ultrasonography could provide this but few data exist on its ability to assess synovial response to therapies. The aim of this study was to examine whether US can detect synovial response to IA corticosteroid (IACS) therapy and to explore associations between synovial characteristics and symptoms. Methods. A total of 35 people with ACR radiographic knee OA were included, including those who required an injection of 80 mg of IA methylprednisolone. All participants completed a visual analogue scale for pain and underwent US of the knee at baseline, 1 and 4 weeks. Minimum clinically important improvement (MCII) in pain was ≥20 mm. Results. One week of data were available for 33 patients (19 received IACS and 14 others). Synovial thickness (ST) decreased in 16 IACS patients and 2 others [mean between-group difference 4.7 mm (95% CI 1.1, 8.2), P = 0.012]. Absolute reduction was not associated with absolute reduction in pain (r = 0.20, P = 0.289), but decreased ST was substantively associated with reduction in pain greater than or equal to the MCII (52.9% vs 23.1%, P = 0.098, φ = 0.30). The power Doppler score decreased in 13 IACS patients and 3 others {median change in IACS patients −1.0 [interquartile range (IQR) −5.0–0.0], others 0.0 [−0.3–1.3], P = 0.004}. Absolute changes in pain and power Doppler score were weakly associated (ρ = 0.36, P = 0.049) and a decreased power Doppler score was associated with reduction in pain greater than or equal to the MCII (64.3% vs 18.8%, P = 0.011, φ = 0.46)

The effect of tofacitinib on residual pain in patients with rheumatoid arthritis and psoriatic arthritis

Objective: Post hoc analysis of pooled data from 9 randomised controlled trials to assess the effect of tofacitinib (oral Janus kinase inhibitor for treatment of rheumatoid arthritis [RA] and psoriatic arthritis [PsA]) on residual pain in patients with RA or PsA with abrogated inflammation. Methods: Patients who received ≥1 dose of tofacitinib 5 mg twice daily (BID), adalimumab or placebo with/without background conventional synthetic disease-modifying antirheumatic drugs and had abrogated inflammation (swollen joint count [SJC]=0 and C reactive protein [CRP] Results: From the total RA/PsA population, 14.9% (382/2568), 17.1% (118/691) and 5.5% (50/909) of patients receiving tofacitinib, adalimumab and placebo, respectively, had abrogated inflammation after 3 months’ therapy. RA/PsA patients with abrogated inflammation receiving tofacitinib/adalimumab had higher baseline CRP versus placebo; RA patients receiving tofacitinib/adalimumab had lower SJC and longer disease duration versus placebo. Median residual pain (VAS) at Month 3 was 17.0, 19.0 and 33.5 in RA patients treated with tofacitinib, adalimumab or placebo, and 24.0, 21.0 and 27.0 in PsA patients, respectively. Residual pain reductions with tofacitinib/adalimumab versus placebo were less prominent in PsA versus RA patients, with no significant differences between tofacitinib/adalimumab, per BNMA. Conclusion: Patients with RA/PsA with abrogated inflammation receiving tofacitinib/adalimumab had greater residual pain reduction versus placebo at Month 3. Results were similar between tofacitinib/adalimumab.</p