Purpose: In a Phase 3 randomized controlled study, differing efficacy Results were observed when triamcinolone acetonide extended-release (TA-ER) was compared to conventional TA crystalline suspension (TAcs) with two different pain measures, average daily pain (ADP) using a 0-10 numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A subscale). Trial enrollment criteria may have contributed to this discrepancy, as a moderate-to-severe ADP score of ≥5 to ≤9 was required at baseline whereas no limitations were placed on baseline WOMAC-A score (0-4 Likert). This allowed for randomization of patients who reported their knee pain as mild via WOMAC-A criteria. This post hoc analysis assessed treatment effects in those patients who reported moderate-to-severe OA pain prior to treatment on both ADP and WOMAC-A scales. Methods: This post hoc analysis included adults (≥40 years) with knee OA (Kellgren-Lawrence Grade 2-3) who reported moderate-to-severe knee OA pain at baseline using both instruments (ADP ≥5 to ≤9 and WOMAC-A ≥2) from a Phase 3 randomized controlled study (concordant pain reporters; n=292). Patients received a single intra-articular injection of TA-ER 32 mg (n=95), TAcs 40 mg (n=100), or Saline-placebo (n=97). Patient-reported ADP-intensity (including area under the effect [AUE] curves), WOMAC-A (pain), WOMAC-B (stiffness), WOMAC-C (function), Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QoL), rescue medication use, Patient Global Impression of Change (PGIC), and adverse events (AEs) were assessed throughout the study. Results: Baseline characteristics (Table 1) and AE profiles were consistent with the full analysis population. TA-ER significantly (P < 0.05) improved ADP scores compared with TAcs (Weeks 5-19) and Saline-placebo (Weeks 1-20) (Figure 1).Table 1Demographic and Baseline Characteristics of Concordant Pain ReportersTA-ER 32 mg n=95Saline-placebo n=97TAcs 40 mg n=100Male, n (%)33 (34.7)37 (38.1)40 (40.0)Age, years, mean (SD)61.1 (9.15)61.3 (8.91)61.0 (10.10)BMI (kg/m2), mean (SD)30.33 (5.042)30.41 (4.847)30.94 (4.748)Years since primary diagnosis, mean (SD)8.3 (7.40)6.3 (5.79)7.6 (6.98)Kellgren-Lawrence grade 2, n (%)49 (51.6)44 (45.4)43 (43.0)Kellgren-Lawrence grade 3, n (%)46 (48.4)53 (54.6)56 (56.0)Kellgren-Lawrence grade 4, n (%)001 (1.0)Weekly ADP intensity score at baseline, n (%)5-5.934 (35.8)28 (28.9)34 (34.0)6-6.932 (33.7)35 (36.1)28 (28.0)≥729 (30.5)34 (35.1)38 (38.0)Weekly ADP intensity score at baseline, mean (SD)6.42 (0.944)6.54 (1.005)6.49 (0.947)WOMAC-A pain score, mean (SD)2.37 (0.339)2.36 (0.348)2.37 (0.316)ADP, average daily pain; BMI, body mass index; SD, standard deviation; TAcs, triamcinolone acetonide crystalline suspension; TA-ER, triamcinolone acetonide extended-release; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index. Open table in a new tab ADP, average daily pain; BMI, body mass index; SD, standard deviation; TAcs, triamcinolone acetonide crystalline suspension; TA-ER, triamcinolone acetonide extended-release; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index. AUEWeeks1-12 and AUEWeeks1-24 were statistically significantly greater for TA-ER compared with TAcs (-47.7 [-94.4, -1.0] and -98.4 [-194.5, -2.3], respectively; P < 0.05 for both) and Saline-placebo (-136.1 [-184.2, -88.0] and -212.1 [-311.1, -113.1], respectively; P < 0.0001 for both). At Week 12, the proportion of patients who reported they had no knee pain (ADP score=0) was greater with TA-ER (∼28%) compared with TAcs (∼8%) (Figure 2); ∼20% of patients who received TA-ER still reported no knee pain at Week 16. TA-ER significantly (P < 0.05) improved WOMAC-A, -B, -C, KOOS-QoL, rescue medication use, and PGIC compared with TAcs and Saline-placebo through at least Weeks 4-12. Conclusions: In patients with knee OA who reported concordant moderate-to-severe pain at baseline across two different reporting instruments, TA-ER provided statistically significant and clinically meaningful pain relief for ≥16 weeks compared with conventional TAcs and Saline-placebo, and also improved stiffness, function, and QoL. Concordant pain reporters were better able to discern treatment effect; Results of this post hoc analysis have implications for study design and patient recruitment of future trials evaluating efficacy of analgesics. Sponsor: This study was funded by Flexion Therapeutics, Inc. (Burlington, MA, USA) .

Purpose: Repeated treatment with intra-articular corticosteroid is often used to manage recurrent osteoarthritis (OA) symptoms. Triamcinolone acetonide extended-release (TA-ER) is an intra-articular injection approved for the treatment of pain in patients with knee OA. We conducted a Phase 3b, single-arm, open-label study and assessed safety and exploratory efficacy endpoints in patients with knee OA treated with repeat administration of TA-ER (NCT03046446). This analysis assessed the clinical benefit of treatment based on patient mobility defined as numbers of steps per day. Methods: Enrolled patients were aged ≥40 years with symptomatic knee OA for ≥6 months, ACR clinical and radiological diagnosis, Kellgren-Lawrence Grade 2-4, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain total sum score ≥6, and index-knee pain for >15 days during the past month. Patients received the 1st injection of TA-ER on Day 1 and the 2nd injection at either Week 12, 16, 20, or 24. This analysis collected patient mobility data within the 1st injection period only. Patient movements were analyzed with a measured function device [Fitbit®] that was worn beginning at least 7 days prior to Day 1 and continuing to the end of Week 12. Weekly average step values were recorded if 3 out of 7 daily values were obtained with a lower threshold of 1000 steps per day. Exploratory efficacy endpoints included WOMAC A (pain) assessed every 4 weeks. A mixed effects model was generated to assess an outcome of change from baseline in steps per day using data from Weeks 4, 8, and 12. The primary independent variable of interest was change from baseline in WOMAC-A average pain scale. Other covariates examined were age, sex, baseline body mass index (BMI), region, month of the start of trial (categorical), visit (continuous, indicating time in weeks from receiving 1st injection), baseline global physical activity questionnaire (GPAQ) values (average MET-minutes of moderate or vigorous physical activity per day), baseline steps per day, and baseline average pain scale. Results: 208 patients were enrolled, most patients were female (55.8%), and 67.8% had radiographic OA severity of Kellgren-Lawrence Grade 3 or 4 at baseline. Mean age was 60.8 years and mean BMI was 31.4 kg/m2. The baseline mean WOMAC pain score was 2.17. Patients treated with TA-ER exhibited an immediate improvement in mobility as shown by increases in weekly mean steps per day (Figure 1) and mean change from baseline in weekly mean steps per day (Figure 2). Treatment with TA-ER was effective with mean changes from baseline in WOMAC-A scores of -1.4, -1.2, and -0.8 at Weeks 4, 8, and 12, respectively. A statistically significant greater change in step count from baseline was observed in association with larger decreases in WOMAC pain scores, male gender, lower BMI, lower baseline GPAQ average MET, and lower baseline steps per day. For every 1-unit decrease (from baseline) in mean WOMAC pain scale, the mean step count per day increased by 339 steps (95% confidence limits, 58 and 620 steps) (Figure 3).View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusions: Patients with knee OA treated with TA-ER exhibited a decrease in pain and increased mobility as measured by their Fitbit. Limitations to this study include incomplete patient adherence to usage of the Fitbit device and that this was an open-label study with no control arm for comparison. Furthermore, it is unclear why the patient population had a relatively high mean number of steps per day at baseline. This study shows the feasibility of using personal fitness monitors to assess the effectiveness of treatments for OA. Sponsor: This study was funded by Flexion Therapeutics (Burlington, MA, USA).

Purpose: Intraarticular corticosteroid (IACS) injection is often used to manage moderate to severe knee osteoarthritis (OA) pain. Retrospective analyses have raised concerns of potential negative effects on joint structure and progression of OA, but these studies were limited by incomplete radiographic reporting and lack of data on prior IACS treatment. Additionally, patients seeking IACS for pain relief may represent a population with more severe OA and ongoing structural progression. There is a need for prospective clinical trials to assess the immediate and long-term effects of IACS in knee OA. Here we present the radiographic safety findings from 2 clinical trials that assessed the effects of single and repeated IACS injections in patients with knee OA. Methods: Study 1 (NCT02357459) was a Phase 3 randomized controlled trial in which patients had a single IA injection of an extended-release formulation of triamcinolone acetonide (TA-ER, 32 mg), a crystalline suspension of TA (TAcs, 40 mg) or saline placebo (PBO). Study 2 (NCT03046446) was a single-arm trial in which patients had IA injection of TA-ER 32 mg at baseline and a second IA injection of TA-ER at either Week 12, 16, 20, or 24, the timing of which was based on the response to the first injection. Both studies enrolled patients aged ≥40 years with symptomatic knee OA ≥6 months and Kellgren-Lawrence Grade (KLG) 2-3 (Study 1) or KLG 2-4 (Study 2). In Study 1, index-knee radiographs (weight-bearing, fixed-flexion technique with standardized knee positioning frame) were obtained at baseline and Week 24 and assessed for chondrolysis based on joint-space narrowing (JSN) using the OARSI method, as well as for development of osteonecrosis (ON) and subchondral insufficiency fracture (SIF). In Study 2, the same radiographic assessments were performed at baseline and Week 52 (or early termination). Chondrolysis was defined as >1 unit increase in JSN within 24 weeks or ≥2 units within 52 weeks. All radiographs were scored by 2 independent, expert radiologists blinded to visit order; the 2 radiologists’ scores for each patient were averaged. Disagreements between the 2 radiologists on ON or SIF were adjudicated by a third expert radiologist. Results: Study 1 enrolled 484 patients, 322 of whom were randomized to TA-ER or TAcs. Baseline characteristics were balanced between arms; 45% of index knees were KL2 (46% TA-ER/TAcs); 55% were KL3 (54% TA-ER/TAcs); 24.8% of patients had prior IACS in the index knee (24.5% TA-ER/TAcs). Study 2 enrolled 208 patients; 32%, 38%, and 30% of index knees were KL2, 3, and 4, respectively; 52% had prior IACS. Treatments were well tolerated in both studies. No patients developed ON in either study. 1 TAcs patient in Study 1 developed SIF noted at Week 24. Only 1 patient from either study showed JSN progression >1 (PBO arm of Study 1: JSN 0 to 2). Of patients in Study 1 with both baseline and week 24 radiographs (140 TA-ER, 145 TAcs, 148 PBO), mild progression of JSN (≤1 unit) was seen in 5.0% of the TA-ER arm, 3.5% of the TAcs arm, and 4.1% of the PBO arm (Table). In Study 2, mild progression of JSN (≤1) occurred in 18.8% of patients, of which 15.2% were only a ½ -point increase within a 52-week period, a follow-up period which was roughly twice as long as that in Study 1.TableRadiographic EvaluationsStudy 1, Baseline - Week 24Study 2, Baseline - Week 52TA-ER 32 mg, n=140, n (%)TAcs 40 mg, n=145, n (%)PBO, n=148, n (%)TA-ER 32 mg, n=165, n (%)JSN increase ≤17 (5.0)5 (3.5)5 (3.4)31 (18.8)JSN increase >1001 (0.7)0Other findings: ON, SIF, RPOA01 (0.7)*Insufficiency fracture noted in one patient at Week 24. JSN, joint space narrowing; ON, osteonecrosis; PBO, saline placebo; RPOA, rapidly progressive osteoarthritis; SIF, subchondral insufficiency fracture; TAcs, triamcinolone acetonide crystalline suspension; TA-ER, triamcinolone acetonide extended-release.00∗ Insufficiency fracture noted in one patient at Week 24. JSN, joint space narrowing; ON, osteonecrosis; PBO, saline placebo; RPOA, rapidly progressive osteoarthritis; SIF, subchondral insufficiency fracture; TAcs, triamcinolone acetonide crystalline suspension; TA-ER, triamcinolone acetonide extended-release. Open table in a new tab Conclusions: Of 450 patients with knee OA who were treated with single or repeated doses of IACS and with radiographic follow-up (84.7% of IACS-dosed patients), no signs of ON or chondrolysis were observed over 6-12 months, and only 1 patient (0.17%) showed evidence suggesting SIF. Of note, no subchondral bone change, osteonecrosis, or radiographically documented rapidly progressive osteoarthritis was identified in patients treated with TA-ER. Larger prospective studies with repeat dosing and longer follow-up, along with the use of additional methods, such as magnetic resonance imaging and biochemical markers, are recommended to define more fully the risks of IACS treatment of knee OA. Sponsor: This study was funded by Flexion Therapeutics (Burlington, MA, USA).

Purpose: Triamcinolone acetonide extended-release (TA-ER) has demonstrated safety and efficacy for providing pain relief following intra-articular (IA) injection in patients with knee osteoarthritis (OA). In practice, repeated treatment with IA corticosteroid is frequently utilized to manage recurrence of OA symptoms. In this Phase 3b, single-arm, open-label study, we assessed safety and exploratory efficacy endpoints in patients with knee OA treated with repeat administration of TA-ER timed to patient symptoms (NCT03046446). This analysis assessed treatment responses to initial and repeat administration using thresholds defined by the Initiative in Methods, Measurements and Pain Assessment in Clinical Trials (IMMPACT) group for clinically important improvements in treatment outcomes. Methods: Patients aged ≥40 years with symptomatic knee OA for ≥6 months, ACR clinical and radiological diagnosis, Kellgren-Lawrence Grade 2-4, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-A (pain) total sum score ≥6, and index-knee pain for >15 days during the past month received the 1st injection of TA-ER on Day 1. Patients received the 2nd injection at the first visit (Week 12, 16, 20, or 24) at which repeat dose criteria were met (ie, patient benefited from and tolerated the 1st injection without safety concerns and was clinically indicated to receive it). Patients who received 2 injections were evaluated every 4 weeks up to Week 52 (ie, 52 weeks after the 1stinjection). Patients who did not benefit from the 1st injection completed the study at Week 12. Patients who did not meet repeat dose criteria by Week 24 completed the study at Week 24. Safety was evaluated via treatment-emergent adverse events (TEAEs) and blinded comparison of index-knee x-rays at Baseline and End of Study. Exploratory efficacy endpoints included WOMAC-A (pain), -B (stiffness), -C (function), and Knee Injury and Osteoarthritis Outcome Score-Quality of Life (KOOS-QoL) assessed every 4 weeks. The proportions of patients meeting IMMPACT criteria for moderate (≥30% improvement from Day 1) and substantial (≥50% improvement from Day 1) response were determined at 4 weeks after each injection. Results: Of 208 patients enrolled, 179 (86.1%) received 2 injections. Of 149 (71.6%) patients completing the trial, 133 had 52 weeks of follow up. Median time to the 2nd injection was 16.6 weeks, with 25.1%, 33.5%, 20.7%, or 20.1% of patients receiving the 2nd injection at Week 12, 16, 20, or 24, respectively. TEAEs and index-knee TEAEs were similar during both injection periods. The most frequently reported TEAEs (≥2%) during the 1st or 2nd injection period for patients who received 2 injections were also similar, and consistent with previously reported studies (ie, arthralgia, upper respiratory tract infection, muscle spasms). Through Week 52, there were no drug-related TEAEs leading to study discontinuation or drug-related serious TEAEs. Most patients (N=165) had Baseline and End of Study x-rays (Week 52 or discontinuation); there were no indications of chondrolysis, osteonecrosis, subchondral insufficiency fractures, or clinically significant subchondral bone changes. Patients experienced similar improvements in WOMAC-A (Figure 1), -B, -C, and KOOS-QoL after both injections suggesting no reduction in efficacy with repeat administration. Overall, 89.7% and 84.8% of patients were considered moderate WOMAC-A responders (≥30% improvement) at 4 weeks after the 1st and 2nd injections, respectively, while 76.6% and 67.8% of patients were considered substantial WOMAC-A responders (≥50% improvement). Proportions of moderate and substantial WOMAC-A responders at 4 weeks after each injection were similar regardless of the time of the 2nd injection (Figure 2). Similar patterns were observed for proportions of patients demonstrating moderate and substantial WOMAC-B, -C, and KOOS-QoL responses. Conclusions: Repeat administration of TA-ER tailored to patient symptoms was well tolerated, was devoid of deleterious effect on joint architecture as determined by x-ray and resulted in substantial improvements in OA symptoms after both injections. Per IMMPACT criteria, more than two-thirds of patients demonstrated a substantial analgesic response with ≥50% improvement from baseline WOMAC-A (pain) value after both the initial and repeat administration of TA-ER. These safety and exploratory efficacy results utilizing validated measures of treatment response suggest that repeat administration TA-ER tailored to patient symptoms may be a potential long-term management strategy for knee OA pain.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Purpose: The hip joint is the second most common site of osteoarthritis (OA), a debilitating disease associated with pain and functional limitations. Hip OA symptoms and progression are linked to the presence of pro-inflammatory mediators and inflammation in synovial tissues. Intra-articular corticosteroids (IACS) have anti-inflammatory effects and are recommended by the Osteoarthritis Research Society International (OARSI) and American Academy of Orthopaedic Surgeons (AAOS) guidelines for the treatment of hip OA. Results from prior studies have demonstrated that IACS provide relief from hip OA pain for up to 8 weeks post-injection . Triamcinolone acetonide extended-release (TA-ER; formerly FX006) is a microsphere-based formulation of triamcinolone acetonide (TA). TA-ER has demonstrated efficacy and safety through 16 weeks post-injection in patients with knee OA and is approved by the United States Food and Drug Administration for the treatment of knee OA pain. Phase 2 pharmacokinetic (PK) studies in patients with knee OA confirmed the extended-release profile of TA-ER, as single or bilateral IA injection showed a gradual increase in plasma TA that plateaued through Hour 24, followed by slow elimination from the systemic circulation. Peak systemic TA concentration was markedly lower following IA injection of TA-ER compared to standard TA crystalline suspension (TAcs). As an initial evaluation in patients with hip OA, we examined the safety and systemic TA exposure following IA injection of TA-ER or TAcs. Methods: This Phase 2, randomized, open-label study (NCT03382262) included patients (≥40 years, BMI ≤40 kg/m2) meeting the ACR clinical/radiographic criteria for hip OA, with symptoms consistent of hip OA for ≥6 months prior to screening and pain in the index joint for >15 days over the last month. Patients were randomized (1:1) to a single IA injection of TA-ER (32 mg) or TAcs (40 mg) and were evaluated for 12 weeks following injection. IA injection was performed using ultrasound guidance. Safety was evaluated based on adverse events (AEs), physical exams, index hip assessments, vital signs, and laboratory evaluations. Blood samples for PK were collected at baseline (within 1 hour prior to injection), at Hours 1-6, 8, 10, and 12 postinjection, and on Days 2, 3, 5, 8, 15, 22, 29, 57, and 85. Plasma TA concentrations were assayed with a validated LC-MS/MS method. Results: Thirty patients with hip OA (TA-ER, n=15; TAcs, n=15) were enrolled/randomized and treated. All treated patients were included in safety analyses. The PK population (TA-ER, n=11; TAcs, n=14) included all patients from the safety population who received a full dose of study drug, completed PK sampling, and had sufficient plasma concentration for PK analysis. Baseline demographic characteristics and OA history were well balanced across the TA-ER and TAcs treatment groups for most parameters. Participants had a mean age of 59.1 (range: 46-73) and 90% were overweight or obese. There were slightly more males in the TAcs group (10/15) than in the TA-ER group (7/15). AE profiles were similar, and both treatments were well tolerated. AEs were reported in 4/15 (TA-ER) and 7/15 (TAcs) patients. There were no serious AEs or AEs leading to treatment discontinuation across treatment groups. No study drug related AEs occurred in the TA-ER group. Index-hip AEs occurred in 1/15 (TA-ER) and 3/15 (TAcs) patients. TA-ER plasma concentrations peaked at median 5.0 hours with a geometric mean (GM) (95% CI) Cmax of 890.4 (415.86-1906.63) pg/mL, whereas TAcs peaked at median 4.0 hours with a GM (95% CI) Cmax of 5549.4 (3085.98-9979.20) pg/mL (Table 1 and Figure 1). Conclusions: In patients with hip OA, a single 32 mg IA injection of TA-ER was generally safe and well tolerated, adding to the established body of evidence in patients with knee OA. The PK profile of TA-ER injected into the hip was consistent with that of single- and bilateral-knee injections, showing some systemic absorption and a plateau in plasma TA concentration through Hour 24, followed by gradual systemic elimination. TA-ER injection into the hip resulted in lower peak plasma levels and reduced systemic exposure relative to TAcs, a pattern similarly observed in knee OA. These findings support initiation of a Phase 3 study to assess the safety and efficacy of TA-ER in patients with hip OA pain.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Knee osteoarthritis (OA) is a painful condition and intra-articular corticosteroids (IACS) are often used to manage OA pain. In Phase 2/3 clinical studies, triamcinolone acetonide extended-release (TA-ER) demonstrated sustained, clinically meaningful pain relief compared with saline-placebo using general Average Daily Pain (ADP)-intensity scores, and compared with saline-placebo and TA crystalline solution (TAcs) using disease-specific Western Ontario and McMaster Universities OA Index (WOMAC-A) measures. As patients may report baseline pain differently using ADP and WOMAC-A measures, we evaluated whether discordant baseline pain reporting influenced measured outcomes. A post hoc analysis of pooled data from 3 Phase 2/3 studies (NCT01487161, NCT02116972, NCT02357459) was conducted to assess treatment effects for patients who reported moderate-to-severe pain at baseline on both pain measures (concordant pain reporters; ADP ≥5 to ≤9 & WOMAC-A ≥2) versus those that reported it only on ADP (discordant pain reporters; ADP ≥5 to ≤9 & WOMAC-A <2). Patients with symptomatic knee OA and baseline ADP-intensity score ≥5 to ≤9 received a single IA injection of TA-ER, TAcs, or saline-placebo. Concordant pain reporters (TA-ER, N=200; TAcs, N =132; saline-placebo, N=172) and discordant pain reporters (TA-ER, N=124; TAcs, N =79; saline-placebo, N=90) were compared using a longitudinal mixed effects model for repeat measures. For concordant pain reporters, least-square-mean (LSM) differences (95% CI) in change from baseline in ADP score at Week 12 were greater (TA-ER vs saline-placebo: -1.11 [−1.61, -0.62]; vs TAcs: -0.45 [-0.98, 0.09]) than for discordant pain reporters (TA-ER vs saline-placebo: -0.54 [(-1.13, 0.06]; vs TAcs: 0.21 [-0.60, 0.64]). The magnitude of the TA-ER treatment effect in concordant pain reporters was approximately twice that in patients with discordant ADP and WOMAC-A pain levels at baseline. As patients inconsistently reporting pain reduced measured treatment effects, these findings should be considered when defining enrollment criteria in future studies. Supported by Flexion Therapeutics Inc. Knee osteoarthritis (OA) is a painful condition and intra-articular corticosteroids (IACS) are often used to manage OA pain. In Phase 2/3 clinical studies, triamcinolone acetonide extended-release (TA-ER) demonstrated sustained, clinically meaningful pain relief compared with saline-placebo using general Average Daily Pain (ADP)-intensity scores, and compared with saline-placebo and TA crystalline solution (TAcs) using disease-specific Western Ontario and McMaster Universities OA Index (WOMAC-A) measures. As patients may report baseline pain differently using ADP and WOMAC-A measures, we evaluated whether discordant baseline pain reporting influenced measured outcomes. A post hoc analysis of pooled data from 3 Phase 2/3 studies (NCT01487161, NCT02116972, NCT02357459) was conducted to assess treatment effects for patients who reported moderate-to-severe pain at baseline on both pain measures (concordant pain reporters; ADP ≥5 to ≤9 & WOMAC-A ≥2) versus those that reported it only on ADP (discordant pain reporters; ADP ≥5 to ≤9 & WOMAC-A <2). Patients with symptomatic knee OA and baseline ADP-intensity score ≥5 to ≤9 received a single IA injection of TA-ER, TAcs, or saline-placebo. Concordant pain reporters (TA-ER, N=200; TAcs, N =132; saline-placebo, N=172) and discordant pain reporters (TA-ER, N=124; TAcs, N =79; saline-placebo, N=90) were compared using a longitudinal mixed effects model for repeat measures. For concordant pain reporters, least-square-mean (LSM) differences (95% CI) in change from baseline in ADP score at Week 12 were greater (TA-ER vs saline-placebo: -1.11 [−1.61, -0.62]; vs TAcs: -0.45 [-0.98, 0.09]) than for discordant pain reporters (TA-ER vs saline-placebo: -0.54 [(-1.13, 0.06]; vs TAcs: 0.21 [-0.60, 0.64]). The magnitude of the TA-ER treatment effect in concordant pain reporters was approximately twice that in patients with discordant ADP and WOMAC-A pain levels at baseline. As patients inconsistently reporting pain reduced measured treatment effects, these findings should be considered when defining enrollment criteria in future studies. Supported by Flexion Therapeutics Inc.