Drug intelligence / Profile preview

methotrexate + sulfasalazine + hydroxychloroquine (AIIMS New Delhi)

Development stage
Phase 4
Lead developer
AIIMS New Delhi
Modality
Small Molecules
Administration
Oral
01

Overview

This combination therapy, frequently referred to as triple therapy, consists of three conventional synthetic disease-modifying antirheumatic drugs (csDMARDs): methotrexate, sulfasalazine, and hydroxychloroquine. It is a well-established intensive treatment strategy for early rheumatoid arthritis (RA), often compared to biological DMARDs or methotrexate monotherapy. Methotrexate serves as the anchor drug, acting as a folate antimetabolite that inhibits dihydrofolate reductase and increases adenosine levels. Sulfasalazine is a prodrug that is cleaved into 5-aminosalicylic acid and sulfapyridine, exerting anti-inflammatory effects through the inhibition of NF-kappaB and prostaglandin synthesis. Hydroxychloroquine is an antimalarial that interferes with endosomal acidification, thereby inhibiting Toll-like receptor (TLR) signaling and antigen presentation. The All India Institute of Medical Sciences (AIIMS) conducted a randomized open-label trial (NCT00565253) to evaluate the efficacy of this triple therapy regimen, both alone and in combination with intravenous pulse methylprednisolone, against methotrexate monotherapy in patients with early RA.

Other names
Triple DMARD therapyAIIMS triple therapy regimenMTX + SSZ + HCQ
02

Targets

TLR7 (Toll-like receptor 7)TLR9 (Toll-like receptor 9)DHFR (Dihydrofolate reductase)PTGS2 (Prostaglandin-Endoperoxide Synthase 2)NF-κB

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