Q4 LONG ANSWER 10M ★ High-yield

Describe the drugs used in rheumatoid arthritis including NSAIDs, DMARDs and biological agents.

Pharmacology · 2nd Professional — Para-Clinical

Approach to Rheumatoid Arthritis

Rheumatoid arthritis is a chronic symmetrical inflammatory polyarthritis. Treatment aims not merely to relieve pain but to suppress inflammation early and prevent joint destruction.

Group	Role
NSAIDs and analgesics	Symptomatic relief only — they do not alter the disease or prevent erosion
Corticosteroids	Rapid and powerful suppression; used as a "bridge" while a DMARD takes effect, or for flares; long-term use is limited by toxicity
Conventional DMARDs	Disease-modifying; slow onset over weeks to months; retard radiological progression
Biological agents	Target specific cytokines or cells; used when conventional DMARDs fail
Targeted synthetic DMARDs	JAK inhibitors — oral, and comparable in efficacy to biologicals

CLINICAL PEARL

The single most important principle is to start a DMARD early. Most erosive damage occurs in the first two years, and it is irreversible. A patient kept comfortable on NSAIDs alone while erosions progress has been failed, however good the symptom control — which is why the modern approach is "treat to target", escalating until remission is achieved.

Conventional Dmards

Drug	Mechanism	Chief toxicity and monitoring
Methotrexate — the anchor drug	Dihydrofolate reductase inhibition; at low weekly doses acts chiefly by adenosine-mediated anti-inflammatory effects	Given once weekly — daily dosing has killed patients. Bone marrow suppression, hepatotoxicity, mucositis, pneumonitis; teratogenic. Folic acid supplementation reduces toxicity. Monitor blood count and liver function
Sulphasalazine	Split by colonic bacteria; the sulphapyridine moiety is active in arthritis	Rash, nausea, leucopenia, reversible oligospermia; safe in pregnancy
Hydroxychloroquine	Raises lysosomal pH and impairs antigen presentation	The safest DMARD; retinopathy with prolonged use — annual ophthalmic screening
Leflunomide	Inhibits dihydro-orotate dehydrogenase → pyrimidine synthesis	Diarrhoea, hepatotoxicity, hypertension; teratogenic with a very long half-life requiring cholestyramine washout
Azathioprine, ciclosporin	Immunosuppression	Marrow suppression; nephrotoxicity

Biological and Targeted Agents

Target	Drugs	Notes
TNF-alpha	Infliximab, adalimumab, etanercept, golimumab	Highly effective; risk of reactivation OF tuberculosis — screening is mandatory before starting, which is critical in India
Interleukin-6 receptor	Tocilizumab	Also used in cytokine release syndrome
B cells (CD20)	Rituximab	Hepatitis B reactivation; infusion reactions
T cell co-stimulation	Abatacept	Modest infection risk
Interleukin-1	Anakinra	Less used in rheumatoid arthritis
JAK enzymes	Tofacitinib, baricitinib	Oral; herpes zoster, thrombosis and cardiovascular signals in older patients

All immunosuppressive agents increase the risk of serious infection, and live vaccines are contraindicated during treatment

Corticosteroids in Arthritis

Extremely effective and extremely toxic with prolonged use — osteoporosis, diabetes, hypertension, cataract, infection, adrenal suppression, proximal myopathy and skin fragility
Used as a bridge, for flares, or by intra-articular injection into one or two troublesome joints, which avoids most systemic effects
Never stop abruptly after prolonged use; the axis is suppressed and adrenal crisis follows
Bone protection from the start — calcium, vitamin D and a bisphosphonate for anyone on long-term steroids

Monitoring Requirements

Drug	Baseline	Ongoing
Methotrexate	Full blood count, liver and renal function, chest radiograph, hepatitis serology	Blood count and liver function every 2–4 weeks initially, then 2–3 monthly
Sulphasalazine	Blood count, liver function, G6PD if indicated	Monthly for 3 months, then periodically
Hydroxychloroquine	Baseline ophthalmic examination	Annual eye examination after 5 years, or earlier if risk factors
Leflunomide	Liver function, blood pressure, blood count	Regular liver function and blood pressure
Anti-TNF agents	Tuberculosis screening (chest radiograph, tuberculin or interferon-gamma release assay), hepatitis B and C, blood count	Vigilance for infection throughout; the risk persists
Rituximab	Hepatitis B serology, immunoglobulins	Immunoglobulin levels before each course

Monitoring is not a formality — it is what makes these drugs usable, and a shared care protocol between specialist and general practitioner is the usual arrangement

Applied Aspects

Write "once weekly" in words on every methotrexate prescription, and confirm the patient understands; inadvertent daily dosing causes fatal marrow suppression and is a recognised prescribing error
Screen for latent tuberculosis and hepatitis B before any anti-TNF agent — these drugs dissolve the granulomas that contain the organism, and in India the background prevalence makes this essential rather than routine
Methotrexate and leflunomide are teratogenic; effective contraception is required, and methotrexate must be stopped some months before conception in both men and women
Annual eye examination on hydroxychloroquine, since retinopathy is irreversible once established
Avoid trimethoprim and co-trimoxazole with methotrexate — both are antifolates and the combination causes profound marrow suppression
Biologicals are expensive and their cost limits access in India; biosimilars have improved availability considerably, and conventional DMARDs used well remain effective for most patients
Combination DMARD therapy is often better than a single agent — methotrexate with sulphasalazine and hydroxychloroquine ("triple therapy") approaches biological efficacy at a fraction of the cost
Assess disease activity objectively with a composite score rather than by impression, and escalate until remission or low activity is reached
Vaccinate before starting immunosuppression — influenza, pneumococcus and hepatitis B; live vaccines are contraindicated once treatment has begun
Any fever in a patient on a biological agent is serious until proved otherwise, and patients must be given clear instructions and a card to show at presentation
Physiotherapy, occupational therapy and joint protection remain part of management and are frequently neglected in favour of drugs alone
Cardiovascular risk is raised in rheumatoid arthritis independently of the drugs, through chronic inflammation, and should be assessed and treated actively
Suppressing inflammation well reduces that risk, so effective DMARD therapy is itself cardiovascular prevention
Steroid-sparing is a constant aim; every month on a steroid adds cumulative harm, and the DMARD exists partly to allow it to be withdrawn
Methotrexate is contraindicated in significant renal impairment, since it is renally cleared and accumulates rapidly to toxic levels
Folic acid is given on a different day from methotrexate, typically the day after, to reduce toxicity without blunting efficacy

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