Immunosuppressants / Biologics / DMARDs

The steroid-sparing maintenance layer. Thiopurines (azathioprine, 6-MP) need 8–12 weeks to work — so they bridge from steroids rather than induce — and require TPMT testing first; methotrexate is teratogenic and has no maintenance role in UC. Anti-TNF agents (infliximab first among them) treat moderate–severe and steroid-refractory disease, are rescue therapy in acute severe UC, and excel in fistulizing CD; vedolizumab blocks gut leukocyte trafficking (slower, gut-selective — ineffective for existing EIMs); ustekinumab, risankizumab, and JAK inhibitors follow anti-TNF failure. Before any of them: vaccination review, TB and hepatitis B/C screening, and shingles vaccination before a JAK inhibitor — then infection watch for the duration.

Azathioprine (with steroids and N-acetylcysteine) is advised against in IPF after PANTHER-IPF (StatPearls). Methotrexate can itself cause ILD — "occurs at any dose; rechallenge generally contraindicated." Antifibrotics (no class page): nintedanib and pirfenidone "can help your lungs work better," "may also help to prevent an acute exacerbation," "and may prolong survival" (NHLBI); StatPearls: antifibrotic therapy "slows FVC decline but does not alter the underlying progressive natural history for most patients." The 2022 guideline suggests nintedanib for progressive pulmonary fibrosis after standard management fails. No doses here.

The disease-modifying therapies (DMTs) are immunosuppressants and immunomodulators aimed at fewer relapses, less MRI activity, and less permanent disability — started promptly at diagnosis — "Immediate treatment initiation upon diagnosis is crucial" (StatPearls) — with the agent chosen by disease activity and safety profile (ECTRIMS/EAN 2018), and considered even for CIS with an abnormal MRI (ECTRIMS/EAN 2018). Classes: injectable interferon-beta (flu-like symptoms 2–8 h after injection; LFT and CBC every 6 months) and glatiramer (post-injection flushing, dyspnea, palpitations that self-resolve in 30 minutes; rotate sites to limit lipoatrophy); oral S1P modulators such as fingolimod (first-dose bradycardia at 4–6 h → observed initiation; macular edema check; VZV immunity screened; rebound on stopping); IV natalizumab (anti-α4-integrin; PML risk by JCV status and duration); IV anti-CD20 ocrelizumab (infusion reactions in a third → premedication; hepatitis B screening; the first therapy approved for PPMS); oral cladribine (TB/HBV/HIV screening; herpes risk; teratogen). Class-wide rules: delay infusions during active infection, complete live vaccines before starting (≥ 4 weeks; 6 weeks for ocrelizumab), and teach the PML warning signs.

The steroid-sparing layer — used alone when steroids are contraindicated or refused, started alongside steroids when steroid risk is high, or added when steroids fail, cause side effects, or cannot be tapered. Azathioprine is the first-line steroid-sparing agent but takes 12–18 months for full effect (monitor WBC and liver tests); mycophenolate, methotrexate, cyclosporine, and tacrolimus are alternatives with weaker evidence. Adjust no more often than every 3–6 months; mycophenolate and methotrexate are contraindicated in pregnancy. Rituximab is an early option in MuSK-MG that fails initial therapy.

Moderate-to-severe psoriasis: methotrexate ("It suppresses the immune system and slows down cell growth and division"), biologics that "block specific immune molecules," and other immunosuppressants for severe cases; systemic pills for severe atopic dermatitis "require close monitoring." Screen for TB and hepatitis before a biologic; monitor blood counts, liver and renal function.

[GCA] Steroid-sparing; [VASC] induction and maintenance. "The ACR recommends tocilizumab, an IL-6 inhibitor antagonist, and high-dose glucocorticoids for patients requiring a corticosteroid-sparing agent" (StatPearls, citing ACR 2021); because it blocks IL-6, "the normalization of CRP and ESR levels can make disease monitoring challenging." For severe GPA and MPA, "rituximab is preferred over cyclophosphamide for induction of remission, administered alongside high-dose glucocorticoids" (StatPearls, citing ACR 2021).

This is the class that changes the disease rather than the symptoms — DMARDs "modulate immune mechanisms to suppress inflammation, prevent joint destruction, and maintain remission," so they change the course of the disease rather than merely managing symptoms. Methotrexate is the anchor, and the 2021 ACR guideline says so at its highest strength: "Methotrexate monotherapy is strongly recommended" over hydroxychloroquine or sulfasalazine, and over biologic or targeted-synthetic monotherapy, for DMARD-naive patients with moderate-to-high disease activity. The dosing fact that must never be blurred: methotrexate for RA is WEEKLY — sources give starting ranges of 7.5 to 15 mg once weekly titrated toward 20 to 25 mg weekly, and "improper daily use of the recommended dose has led to fatal toxicity." Folate supplementation of 1 mg/day or 5 to 7 mg weekly "should be considered for all patients to prevent bone marrow suppression." Contraindications are absolute in pregnancy and breastfeeding, in chronic liver disease, cirrhosis, alcoholic hepatitis or active alcohol use disorder, in blood dyscrasias and active infection, with dose reduction below a GFR of 60 and avoidance below 15. Monitor CBC, creatinine and transaminases weekly for 4 weeks then at least bimonthly, and treat mouth ulcers as a toxicity signal. When methotrexate at maximum tolerated dose is not enough, ACR 2021 says "addition of a bDMARD or tsDMARD is conditionally recommended over triple therapy" — TNF inhibitors, IL-6 inhibitors, abatacept, rituximab or a JAK inhibitor. Before any biologic: screen for hepatitis B and C and tuberculosis, with latent TB treated for at least 1 month first, and never give a live vaccine. When the patient reaches target for 6 months, ACR 2021 gives a three-step hierarchy, and the first step is to change nothing: (1) continuing all DMARDs at the current dose is conditionally recommended over dose reduction; (2) if a reduction is undertaken, dose reduction is conditionally recommended over gradual discontinuation; and (3) gradual discontinuation over abrupt discontinuation. Reaching target is not itself a trigger to taper.

[Scleroderma] By organ: cyclophosphamide and mycophenolate (lung and skin), methotrexate (skin, arthritis, myositis), azathioprine, hydroxychloroquine (skin) — though "a generalized lack of large randomized controlled trials undermines their efficacy." Nintedanib is FDA-approved for SSc lung disease. [Sjögren’s] Only for extraglandular disease: "Systemic treatment is generally unnecessary for isolated dry eye (xerophthalmia) or dry mouth (xerostomia)"; for moderate to severe extraglandular disease, hydroxychloroquine and steroid-sparing agents (methotrexate, azathioprine, mycophenolate, leflunomide). Topical cyclosporine or tacrolimus eye drops treat dry eye.

A risk factor, not a treatment. "Immunosuppression after organ transplant is associated with an increased risk of SCC and BCC"; transplant recipients need close skin surveillance.

Two jobs at once: control organ-threatening disease, and get the patient off steroids — "corticosteroid-sparing medications" are named as the mainstay for ongoing arthritis, and inadequate response or glucocorticoid dependency is itself the trigger to introduce them earlier. Choice follows the organ: methotrexate, mycophenolate mofetil or azathioprine for arthritis beyond hydroxychloroquine; methotrexate then mycophenolate, belimumab or anifrolumab for resistant cutaneous disease; high-dose corticosteroids plus cyclophosphamide, azathioprine or rituximab for inflammatory CNS disease; mycophenolate or rituximab for interstitial lung disease. Lupus nephritis is where this class is unambiguously first-line: new or flaring Class III–IV disease now gets triple therapy: glucocorticoids plus mycophenolate with belimumab or a calcineurin inhibitor such as voclosporin, or cyclophosphamide followed by mycophenolate plus belimumab (ACR, as reported by StatPearls), with an anti-CD20 agent such as rituximab or obinutuzumab for refractory disease, always with hydroxychloroquine and always comanaged with a nephrologist. Maintenance runs at least 3 years in nephritis, and immunosuppression is generally continued 3 to 5 years with sustained remission before tapering. The price is infection risk — serious infection is one of the leading causes of morbidity and mortality in lupus — so every fever is taken seriously. In pregnancy, disease should be quiescent 6 months or more before conception, teratogenic agents switched 4 to 6 months ahead, and azathioprine used as the steroid-sparing agent.

Tacrolimus (calcineurin inhibitor) — "indicated for the prophylaxis of organ rejection"; narrow therapeutic index; trough drawn "within 30 minutes before the next dose"; take it consistently with or without food "the same way each time"; no grapefruit; many CYP3A interactions; watch creatinine, K, Mg, glucose, BP, tremor and PRES. Immediate- and extended-release forms are not interchangeable — "Medication errors, including substitution and dispensing errors" have occurred. Cyclosporine — nephrotoxicity, hyperkalemia, hypomagnesemia, dyslipidemia and hypertrichosis; levels monitored. Mycophenolate — boxed warning for "EMBRYOFETAL TOXICITY, MALIGNANCIES and SERIOUS INFECTIONS"; neutropenia and GI bleeding; recommended "on an empty stomach" (with food "if necessary" in stable patients).

The original β-lactams — bactericidal cell-wall inhibitors. The defining nursing job is screening for and recognizing allergy, from rash to anaphylaxis.

β-lactam cousins of penicillin, organized by generation — each generation trades some gram-positive reach for broader gram-negative coverage.

Powerful, broad-spectrum DNA-synthesis blockers — but a boxed warning for disabling tendon, nerve, and CNS effects means they’re reserved when alternatives exist.

Suppress viral replication rather than kill viruses outright. The nursing essentials: hydrate with acyclovir, start early (flu within 48 h), and remember most antivirals suppress — they don’t cure.

Powerful IV drugs for serious Gram-negative infection — but nephrotoxic and ototoxic. Levels matter.

Broad, generally safe protein-synthesis inhibitors — a penicillin-allergy alternative. Watch QT and CYP3A4.