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# Conventional disease-modifying antirheumatic drugs (DMARDs)

Slow-acting medicines that calm the immune attack in rheumatoid arthritis and lupus and protect the joints over months, not hours.

Updated 2026-11-01

## What they are

Small-molecule drugs that change the course of rheumatoid arthritis and other autoimmune diseases instead of only easing pain. Methotrexate is the anchor; hydroxychloroquine, leflunomide and sulfasalazine are the other main members. Their effect takes weeks to months to appear.

## Mechanism of action

Each works differently. Hydroxychloroquine concentrates in acidic compartments of immune cells and dampens immune signalling by mechanisms not fully known. Leflunomide's active metabolite inhibits dihydroorotate dehydrogenase, so activated lymphocytes cannot make enough pyrimidines to proliferate. Methotrexate inhibits folate-dependent enzymes.

Target: Several: acidic vesicles (hydroxychloroquine), dihydroorotate dehydrogenase (leflunomide), folate enzymes (methotrexate)

## Key points

- Their benefit appears slowly, over weeks to months.
- Hydroxychloroquine: retinal toxicity related to cumulative dose; regular eye examinations.
- Hydroxychloroquine is a cornerstone of lupus treatment.
- Leflunomide: hepatotoxic and teratogenic; it stays in the body for a long time unless an elimination procedure is used.
- Methotrexate and leflunomide are both teratogenic; hydroxychloroquine is generally considered compatible with pregnancy in lupus.

## Drugs in this class

- [**Hydroxychloroquine** An old antimalarial that is now a mainstay for lupus and rheumatoid arthritis. Long use needs regular eye checks… Acidic intracellular vesicles (lysosomes; the malaria parasite's food vacuole)](https://durgical.com/en/pharmacology/hydroxychloroquine/)
- [**Leflunomide** A rheumatoid arthritis tablet that stops activated lymphocytes making pyrimidines. It stays in the body for months and… Dihydroorotate dehydrogenase (DHODH)](https://durgical.com/en/pharmacology/leflunomide/)

## Others in the class

- sulfasalazina

## Test yourself

Think of the answer, then tap the question to see it.

## What separates a DMARD from an anti-inflammatory painkiller in rheumatoid arthritis?

A DMARD changes the disease course and slows joint damage over months; an NSAID only eases pain and swelling while it is taken.

## Which examination is repeated during long-term hydroxychloroquine and why?

A retinal (eye) examination, because the drug can cause irreversible retinopathy related to cumulative dose and duration.

## Which enzyme does teriflunomide, the active metabolite of leflunomide, inhibit?

Dihydroorotate dehydrogenase, in the de novo synthesis of pyrimidines.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - HYDROXYCHLOROQUINE SULFATE tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cf4b1912-9806-4ef3-bf17-152a96d75bbc) (DailyMed (U.S. National Library of Medicine), 2024); [DailyMed - LEFLUNOMIDE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=91712aad-d96c-4ef0-97e7-b31ed18ca6d8) (DailyMed (U.S. National Library of Medicine), 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/conventional-disease-modifying-antirheumatic-drugs/