The Drug-Induced Respiratory Disease Website and App

TNF-alpha antagonists / inhibitors

Review on biologicals: PMID 15127338, 16887405, 19634383, 21531225, 21597375, 22718926, 24101863. Guide when starting treatmenta at PMID 24667275. Robust evidence for causality exists regarding opportunistic infections, including bacterial infection and tuberculosis, and for the devlopment of autoimmunity. As for ILD and serosal involvement, although a temporal association with exposure may exist in some cases, evidence for causality is tenuous or disputed. For those cases exposed to methotrexate concomitantly, drug causality assessment can be difficult. Ruling out an infection is important in all cases. Risk assessment for TB well-delineated but suboptimally implemented (PMID 19634383). Tuberculosis reinfection can occur despite a history of optimal prophylaxis at onset of treatment. Anti-TNF agent-induced infection available at PMID 15127338, 15523118, 18241628, 20381217, 24655394 and 25630559

Frequency - Incidence

Incidence of respiratory adverse event(s) due to the specific drug as assessed by number of reported/published cases in the literature. Red digits in stars indicate: 0 = Very rare, questionable signal · 1 = < 10 cases · 2 = 10-50 cases · 3 = 50–100 cases · 4 = 100-200 cases · 5 = >200 cases

Evidence level/grade

Evidence level for respiratory adverse event(s) due to the specific drug as estimated using Hill’s (1965), Naranjo’s (1981), and Bégaud’s (1985) criteria applied to published cases. Blue digits in stars indicate: 0 = Questionable · 1 = Low · 2 = Moderate · 3 = Robust · 4 = Definite · 5 = Unquestionable, pathognomonic

I - Interstitial/parenchymal lung disease

I.a

Pneumonitis (ILD)

I.b

Pneumonitis (ILD), acute and/or severe (may cause ARDS)

I.c

Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

I.d

Acute eosinophilic pneumonia (AEP)

I.g

Pulmonary fibrosis

I.n

ILD with a granulomatous component

I.r

Pulmonary nodulosis

I.x

Rapidly progressive ILD/pulmonary fibrosis (Hamman-Rich syndrome)

I.z

Progression, acceleration or exacerbation of preexisting ILD/fibrosis

III - Pulmonary/alveolar./airway hemorrhage/bleeding

III.a

Alveolar hemorrhage (AH), diffuse AH (DAH)

III.d

Alveolar hemorrhage, diffuse (ANCA-positive/-related)

IV - Airway involvement

IV.a

Bronchospasm - Wheezing - Asthma

VI - Pleural and/or pericardial involvement

VI.a

Pleural effusion (uni- or bilateral) (can accompany DI-LDs)

VI.d

Pleural/pericardial effusion, ANA positive (DI lupus)

IX - Neuromuscular / CNS involvement - Disordered breathing (during sleep)

IX.q

Obstructive sleep apnea

IX.t

CNS involvement/dysfunction/damage

X - Systemic/Distant conditions, syndromes and reactions

X.b

Antiphospholipid antibodies w/wo the APL syndrome

X.d

Lupus - Lupus syndrome (see also Vd)

X.e

Autoimmunity-Autoimmune conditions (+ANA, +anti-ds-DNA, +ANCAs, other auto-Abs)

X.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)

X.i

Hypersensitivity reaction (may manifest with fever and/or skin, throat or airway involvement)

X.l

Myopathy-Myositis-Polymyositis (see also under Xba)

X.m

Sarcoid-like granulomatosis (endo-/extrathoracic)

X.o

Vascultis (pulmonary, extrathoracic or systemic)-ANCA status unknown or negative)

X.r

Serum sickness-like reaction

X.u

Vasculitis, pulmonary (w/wo AH), extrapulmonary, systemic: ANCA-positive

X.z

ANCA positivity. Subclinical or with clinical manifestations

X.ag

Antisynthetase antibodies (ASA) - ASA syndrome

XII - Cardiovascular involvement / toxicity

XII.a

Left or biventricular dysfunction/failure

XIX - Pathology

XIX.bo

Path: Pleural granulomas

XIX.bx

Path: Granulomatous lymphadenopathy

XX - Infections & related conditions

XX.a

Respiratory tract infection incl. pneumonia

XX.b

Opportunistic pulmonary/systemic infections

XX.d

Pneumocystis jiroveci pulmonary colonization

XX.e

Pneumocystis jiroveci pneumonia

XX.f

Tuberculosis, miliary

XX.g

Tuberculosis (pulmonary, pulmonary, extrapulmonary or disseminated). Reactivation or de novo

XX.h

Nontuberculous pulmonary mycobacterial infection/superinfection

XX.m

Fungal airway infection

XX.n

Legionella pneumophila pneumonia

XX.q

Viral pneumonia

XX.r

Fungal infection (pulmonary/extrapulmonary)

XX.u

Strongyloides stercoralis hyperinfection (w/wo DAH)

XX.x

Cryptococcus pulmonary and/or systemic infection

XX.y

Histoplamosis (reactivation)

XX.aa

Protozoan infection (incl. leishmaniasis)

XX.aj

Mycobacterium leprae infection (Leprosy)