OP0170 PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF A TRANSDERMAL ALKALINIZING AND PAIN-RELIEVING TREATMENT FOR REDUCING PAIN ASSOCIATED WITH AN ACUTE GOUT FLARE

Abstract

BackgroundMonosodium urate (MSU) deposition is pathognomonic for gouty arthropathy. MSU crystal formation and dissolution is affected by pH and theoretically, alkalinizing agents (eg, sodium bicarbonate, NaHCO₃) that raise the joint microenvironment pH, could facilitate MSU crystal dissolution1 and decrease the pain of an acute gout flare. However, oral NaHCO₃ use is fraught with intolerable gastrointestinal side effects.ObjectivesTo determine if NaHCO₃ in a patented transdermal formulation could effectively and safely reduce the pain of an acute gout flare.MethodsA Phase 2a prospective, double-blind, randomized, placebo-controlled study enrolled 418 subjects across 20 US sites. Patients with a diagnosis of gout using ACR/EULAR criteria (Score ≥ 8), ages 18-75, history of ≥ 2 gout flares in 12 months prior to randomization and on stable doses of urate lowering therapy were included. Exclusion criteria were BMI > 40kg/m2, > 12 gout flares in the year prior to randomization, history of rheumatoid arthritis, psoriatic arthritis, evidence of septic arthritis, acute polyarticular gout (≥ 4 joints), and arthritis of any other cause. Patients were randomized to receive placebo lotion or transdermal NaHCO₃. Upon flare they initiated colchicine (1.2 mg followed by 0.6 mg 1 hour later) and applied study product to the limb of the affected joint. Outcome measures included pain-numeric rating scale (NRS, 0-10), time to resolution of pain (50% reduction), rescue medication use, joint tenderness, and physical function (PROMIS PF-20). Data were collected in patient diaries for the pain and PROMIS measures at several time points from baseline through Day 7, as were adverse events. Statistical analyses utilized ANCOVA (baseline pain as a covariate), Kaplan-Meier curves for homogeneity, and two-proportion z-test, all with α=0.05.Results98 patients had a gout flare during the 14-month study period. Those in the active arm (ITT, N=48) had an overall responder rate of 94.5% vs. 79.3% (p=0.01) in the placebo arm (ITT, N=50) over the 7-day follow up. Rescue medication use was lower in the active arm vs. placebo (6.3% vs. 20.0%, p=0.02); and PROMIS PF-20 showed greater improvements over 7 days (22.2 vs. 16.7 points, p=0.05). The most common adverse event was hypertension (14.2%) with no significant difference between arms. Per protocol analyses were conducted to adjust for adherence on Day 1 for time to resolution of pain (Figure 1) and additional 24hr endpoints (Table 1).Table 1.Key 24hr Endpoints (Per Protocol, n = 57)Active (n = 28)Placebo (n = 29)P valueMedian time to resolution, hrs124720.03Change in 24hr PROMIS PF-20 score216.79.40.01Physician-assessed moderate-to-severe joint tenderness 24hr328.0%57.1%0.021≥ 50% reduction in pain; K-M Est.; Subjects using rescue medication, discontinuing study drug, or missing pain scores censored2Consists of 20, 0-5-point questions; higher scores indicate better function3LIKERT: 0 (no pain), 1 (pain), 2 (wincing), 3 (wincing and withdrawal)Figure 1.Time to resolution of pain1 (per protocol population, n = 57)ConclusionTransdermal NaHCO₃ reduced the pain intensity and duration of an acute gout flare with higher overall response rates, faster time to resolution, improvements in physical function and a reduction in rescue medication use. The lack of adverse events makes this topical a promising therapeutic choice; especially during debilitating acute gout flares in patients with concomitant comorbidities.