Immunomodulators: Practice MCQs

What is the single mechanistic step that makes cyclosporine and tacrolimus one pharmacological class despite being chemically unrelated?

1. Both are metabolised by the same hepatic enzyme
2. Both immunophilin-drug complexes inhibit calcineurin, blocking NFAT-driven interleukin-2 gene transcription
3. Both bind the same cell-surface cytokine receptor
4. Both are B-cell-depleting antibodies

Why can Sandimmune and Neoral cyclosporine not be substituted for each other on a milligram-to-milligram basis?

1. They are different drugs entirely
2. Neoral has increased bioavailability compared with Sandimmune, so the two formulations are not bioequivalent
3. Sandimmune is more potent than Neoral
4. There is no clinically meaningful difference between them

Which food/drink interaction is specifically flagged for cyclosporine?

1. Cranberry juice
2. Grapefruit and grapefruit juice
3. Orange juice
4. Green tea

New-onset diabetes after transplant is a labelled risk most prominently associated with which calcineurin inhibitor in the material reviewed here?

1. Cyclosporine
2. Tacrolimus
3. Neither drug
4. Both equally, with identical labelled emphasis

Why is therapeutic drug monitoring of trough blood concentrations central to using either calcineurin inhibitor safely?

1. Because it is a regulatory formality with no clinical basis
2. Because the gap between effective immunosuppression and nephrotoxic/neurotoxic levels is narrow for both drugs
3. Because both drugs have no dose-related toxicity at all
4. Because oral absorption of both drugs is always complete and predictable

A rheumatoid arthritis patient is found taking their methotrexate tablet every day instead of once a week. What is the clinical significance?

1. None — methotrexate has a wide therapeutic index at any interval
2. This is a recognised cause of severe, potentially fatal toxicity, and is exactly the error the label requires prescribers and pharmacists to warn against
3. It only matters if the patient also takes NSAIDs
4. Daily dosing is actually the correct schedule for rheumatoid arthritis

Which conventional DMARD's boxed warning includes both teratogenicity and hepatotoxicity, with a distinct elimination procedure for its active metabolite?

1. Hydroxychloroquine
2. Sulfasalazine
3. Leflunomide
4. Methotrexate

Why is hydroxychloroquine retinal screening performed before symptoms appear rather than after?

1. Because the retinal damage is entirely reversible once caught
2. Because irreversible damage can continue to progress even after the drug is stopped
3. Because screening is only a regulatory formality with no clinical basis
4. Because retinal toxicity always presents with pain, making screening unnecessary

Which contraindication is specific to sulfasalazine and not shared by the rest of the conventional DMARD class?

1. Pregnancy
2. True sulfonamide or salicylate hypersensitivity
3. Chronic liver disease
4. Immunodeficiency syndromes

What is the mechanistic basis for calling methotrexate, hydroxychloroquine, sulfasalazine and leflunomide a single class of "conventional synthetic DMARDs"?

1. They all inhibit the same intracellular kinase
2. They all bind the same cell-surface receptor
3. They are grouped by being small synthetic molecules that predate the biologic and JAK-inhibitor era, not by a shared mechanism
4. They are all metabolised by the same hepatic enzyme

A patient on leflunomide develops a new nonproductive cough with worsening dyspnoea. What does this most urgently raise concern for?

1. A benign, self-limiting side effect requiring no action
2. Interstitial lung disease, a separately labelled and potentially fatal risk of leflunomide
3. Normal drug-related fatigue
4. An expected and harmless finding in all conventional DMARDs

Which statement about combining conventional DMARDs with other drug classes in rheumatoid arthritis is correct?

1. Combining a conventional DMARD with a biologic DMARD is standard and considered safe
2. Combining two biologic DMARDs together is standard practice
3. A biologic DMARD is never combined with any conventional DMARD
4. JAK inhibitors are always combined with a biologic DMARD

Which statement correctly distinguishes the FDA-approved indications of azathioprine and mycophenolate mofetil?

1. Both are FDA-approved for rheumatoid arthritis
2. Azathioprine is FDA-approved for rheumatoid arthritis and transplant rejection prophylaxis; mycophenolate mofetil is approved only for transplant rejection prophylaxis
3. Mycophenolate mofetil is FDA-approved for rheumatoid arthritis and azathioprine is not
4. Neither drug has an FDA-approved indication outside oncology

What is the mechanistic basis for mycophenolic acid's claimed relative selectivity for lymphocytes?

1. It binds a lymphocyte-specific cell-surface receptor
2. Activated T and B lymphocytes depend more heavily on the de novo purine synthesis pathway that IMPDH inhibition blocks, compared with most other proliferating cells
3. It is only absorbed into lymphocytes and no other cell type
4. It has no selectivity and is equally toxic to all dividing cells

A patient with absent TPMT activity is started on a conventional dose of azathioprine. What is the clinical concern?

1. No concern — TPMT status is irrelevant to azathioprine dosing
2. Severe, life-threatening myelotoxicity, since deaths from pancytopenia have been reported in this exact scenario
3. Reduced drug efficacy only, with no safety implication
4. Increased risk of teratogenicity specifically

Which drug interaction with azathioprine requires dose reduction because of a shared metabolic pathway?

1. Allopurinol, which inhibits xanthine oxidase and raises azathioprine metabolite exposure
2. Paracetamol, which has no relevant interaction
3. Amoxicillin, which increases azathioprine absorption
4. Omeprazole, which blocks azathioprine's hepatic conversion

What does mycophenolate mofetil's REMS programme specifically require?

1. Annual liver biopsy for all patients
2. Pregnancy testing and documented contraception for females of reproductive potential, before and during treatment
3. Weekly chest X-rays
4. Genetic testing for TPMT deficiency

Structurally, what distinguishes etanercept from infliximab, adalimumab and golimumab?

1. Etanercept is a small molecule, the others are antibodies
2. Etanercept is a soluble TNF-receptor fusion protein, the others are monoclonal antibodies against TNF-alpha
3. All four are chemically identical monoclonal antibodies
4. Etanercept is the only one given intravenously

Hepatosplenic T-cell lymphoma has been reported most specifically with which combination?

1. Etanercept alone in rheumatoid arthritis
2. Infliximab or adalimumab plus azathioprine/6-mercaptopurine in adolescent/young adult male IBD patients
3. Abatacept in elderly patients with COPD
4. Rituximab in first-line rheumatoid arthritis

Which set of boxed warnings belongs to rituximab rather than to the TNF inhibitors?

1. Serious infection including tuberculosis, and paediatric malignancy
2. Fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B reactivation, and progressive multifocal leukoencephalopathy
3. Embryofetal toxicity and hepatotoxicity
4. Major adverse cardiovascular events and thrombosis

What happened in trials when abatacept was combined with a TNF antagonist?

1. Serious infections fell compared with TNF-antagonist monotherapy
2. Serious infections rose from 0.8% to 4.4% compared with TNF-antagonist monotherapy
3. No difference in infection rates was observed
4. The combination improved efficacy with no added risk

A patient is being considered for rituximab for rheumatoid arthritis. What does its FDA label require to have already happened?

1. Nothing — rituximab is first-line therapy
2. An inadequate response to one or more TNF antagonist therapies, with rituximab then used in combination with methotrexate
3. Prior treatment with abatacept specifically
4. A positive tuberculosis test

Which biologic DMARD in this class is the only one with no absolute contraindication listed in its own FDA label?

1. Etanercept
2. Infliximab
3. Abatacept
4. Rituximab

Why is tuberculosis screening required before starting a TNF inhibitor or abatacept?

1. Because these drugs are directly toxic to Mycobacterium tuberculosis
2. Because they interfere with immune surveillance that normally contains latent TB, and patients on this class have frequently presented with disseminated or extrapulmonary disease
3. Because TB screening is only a billing requirement with no clinical basis
4. Because TNF inhibitors cure latent TB on their own

What structurally distinguishes JAK inhibitors from biologic DMARDs?

1. JAK inhibitors are injectable proteins like biologics
2. JAK inhibitors are oral small molecules that block intracellular signalling, while biologics are typically proteins that bind an extracellular target
3. JAK inhibitors have no immunosuppressive effect
4. There is no meaningful difference between the two categories

Which JAK inhibitor was the drug actually studied in the ORAL Surveillance trial that produced the class's boxed warning?

1. Baricitinib
2. Upadacitinib
3. Tofacitinib
4. All three were studied together in one arm

What do the baricitinib and upadacitinib labels say about their own MACE and mortality risk relative to tofacitinib's trial findings?

1. That the risk is proven to be identical to tofacitinib's
2. That these two drugs have not been studied in a trial of comparable size, so the risk has not been adequately evaluated for them specifically
3. That these two drugs are proven safer than tofacitinib
4. That the boxed warning does not apply to them

Which of the following is a labelled restriction specific to tofacitinib rather than the whole JAK-inhibitor class?

1. A requirement for lipid monitoring
2. The higher-dose regimens are not recommended for RA, PsA, AS or pcJIA
3. A requirement for latent TB testing
4. Monitoring for neutropenia

In ORAL Surveillance, the increased lung cancer rate with tofacitinib was specifically observed in which subgroup?

1. All patients regardless of smoking history
2. Current or past smokers
3. Only patients under 50
4. Only patients never exposed to a TNF blocker

Which pharmacokinetic property most differentiates baricitinib from tofacitinib and upadacitinib within this class?

1. Baricitinib is eliminated primarily by the kidney, while the other two rely mainly on hepatic CYP3A4 metabolism
2. Baricitinib is not absorbed orally
3. Baricitinib has no monitoring requirements
4. Baricitinib is a biologic protein, not a small molecule