1587: Efficacy and Safety of Curcumin in Maintaining Remission During Disease Modifying Anti Rheumatic Drug Withdrawal in Rheumatoid Arthritis at 52 Weeks: Phase III Double-Blind Randomized Placebo Controlled Trial

Padmanabha Shenoy¹, Sreeja Bhatt², Reshma Reji², Anuroopa Vijayan², Manju Mohanan², Sakir Ahmed³, Pankti Mehta⁴ and Aby Paul², ¹Centre for Arthritis and Rheumatism Excellence (CARE), Cochi, India, ²Centre for arthritis and Rheumatism excellence, Nettor, Kerala, Kochi, India, ³Kalinga Institute of Medical Sciences, Bhubaneswar, India, ⁴King George's Medical University, Lucknow, India

Background/Purpose: Curcumin, extracted from Curcuma (Turmeric) spices, has been shown to have anti-inflammatory properties in animal models of arthritis and in observational studies(1,2). Despite the lack of well controlled studies, it is widely used as a dietary supplement by patients with Rheumatoid Arthritis (RA) across the world. DMARD-free remission is maintained in less than one-fourth of patients with RA.

We explored the potential of Curcumin in maintaining remission in patients with RA while tapering conventional synthetic DMARDs (csDMARDS).

Methods: In this single centre, patient and investigator blinded trial, adults with RA in sustained remission [DAS-28 < 2.6 and SDAI ≤ 3.3 and TJC (44) < 0 and SJC (44) < 0 confirmed during two consecutive visits] for more than 6 months were randomised in a 1:1 ratio to receive standardized Curcumin- piperine preparation (1 gm Curcumin with 5 mg Piperine twice daily) or matching placebo . cs-DMARDS were tapered and stopped sequentially during each visit as per a fixed protocol in the following sequence: Methotrexate >Leflunomide > Sulfasalazine > Hydroxychloroquine. Patients who had required biological DMARDs, corticosteroids or NSAIDs in last 6 months or those already on curcumin supplements had been excluded before randomization.

The primary outcome was flare-free survival at the end of 52 weeks (per protocol analysis). Standard definitions were used to define flares. Patients with flares received rescue therapy and were excluded from further follow-up. Secondary outcome measures were time to flare, safety of curcumin, the estimation of serum curcuminoid levels and its correlation with flares.(Trial registration no: CTRI/2018/04/013279)

Results: After screening 274 patients with RA, 200 were randomized 1:1 to Curcumin or to placebo groups. Baseline characteristics were comparable between the groups [Table 1]. Per-protocol analysis included 92 participants in the curcumin group and 93 in the placebo group. At 52 weeks follow-up, flare-free survival was same between both groups [Figure 1; Log-rank test: p=0.76]. The median time to flare in both groups was statistically same [Curcumin group: 219 days (IQR: 123) versus 214 days (95.8); p=0.067].

Adverse effects were similar across both groups with one each of infection and benign tumour in the curcumin group; and 2 new diagnoses of psoriasis in the placebo group.

The curcuminoid levels , estimated in 72/92 in the Curcumin group and 70/93 in the placebo group showed a significantly higher serum level of curcuminoids in the interventional arm [ Median (IQR): 19.70 ng/ml (31-12) vs 0.00(0-3.0), P =< 0.01], confirming the good bioavailability of the preparation used. Cox proportionate regression modelling showed that flares were independent of serum curcuminoid levels [Adjusted HR=0.99(95%CI: 0.969-1.0); p=0.5]. The model also showed the lack of association of flare-free survival with age, sex, seropositivity, or DMARDs used at baseline [Figure 2].

Conclusion: In RA patients who are in remission in whom csDMARDs were being systematically tapered, the addition of Curcumin, despite having a good bioavailability, did not affect the flare-free survival or time to flare.
Figure 1: Flare-Free Survival in Patients with Rheumatoid Arthritis on Curcumin Versus Placebo at 52 weeks Follow-up

Figure 2: Adjusted Hazard Ratios for Flare in Patients with Rheumatoid Arthritis as per Cox Proportionate Regression Modelling

Table 1: Baseline Characteristics in Trial versus Placebo Groups
Disclosures: P. Shenoy, None; S. Bhatt, None; R. Reji, None; A. Vijayan, None; M. Mohanan, None; S. Ahmed, DrReddy, Novartis, Pfizer, Janssen, Cipla; P. Mehta, None; A. Paul, None.