eMedicine Specialties > Ophthalmology > Iris & Ciliary Body
Uveitis, Juvenile Idiopathic Arthritis: Treatment & Medication
Updated: Oct 24, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The management of patients with JIA-associated uveitis should be approached in a stepladder manner.14,15,16,17
- Treatment initially should begin with topical corticosteroids. Most patients would respond to this initial treatment. Around 20% of patients with JIA-associated uveitis have little or no response.
- The presence of vitreous cells, severe disease, or chronic inflammation increases the risk for CME. These patients may be given additional nonsteroidal anti-inflammatory drugs (NSAIDs).
- The decision to use regional corticosteroids depends on the patient's response to topical therapy and/or the presence of posterior segment involvement. Monocular involvement also weighs in more toward regional corticosteroid use. Bilaterality may favor the use of systemic corticosteroids.
- Systemic immunomodulatory agents may be useful for patients with limited or no response to systemic corticosteroids or those who develop unacceptable adverse effects.9,18,19,20,21,22,23,24,25,26
Surgical Care
- Ethylenediaminetetraacetic acid (EDTA) chelation for band keratopathy may be performed. The procedural technique for EDTA chelation is outlined below.
- This procedure is ideally performed in a minor operating room setting using an operating microscope as well as topical (proparacaine or tetracaine) anesthesia.
- Apply a self-retaining lid speculum to keep the eyelids open.
- Perform epithelial debridement using an ophthalmic surgical blade (blade 15) or a sharp spatula to expose the underlying calcium.
- Apply Weck-cel sponges, soaked with 0.05 mol, 1.5% neutral disodium EDTA, to the corneal surface. A corneal well, similar to a corneal trephine, may be used to soak the exposed calcium to EDTA.
- Using a blunt (Paton) spatula, firmly scrape the corneal surface to remove calcium deposits.
- Repeat the procedure of soaking and scraping as often as necessary to clear up the central visual axis. Usually, thin calcium deposits are dissolved in 5 minutes. Sometimes, it may take as long as 30-45 minutes to remove thick plaques.
- Place topical antibiotic and nonsteroidal agents on the cornea. Use the topical medications until the bandage contact lenses are in place.
- Place a bandage contact lens over the cornea. Maintain the bandage contact lens for 1-2 weeks until the cornea is completely reepithelialized.
- Cataract surgery is reserved for those patients with poor visual acuity or in cases where the vitreous and retina cannot be visualized. The decision to perform cataract surgery should be weighed against the risks and benefits. Routine placement of an intraocular lens is contraindicated in most patients with JIA.27,28,29
- Glaucoma surgery is reserved for patients in whom medical therapy has failed and evidence exists of progressive optic nerve damage.
- If vitreous debris prevents optimal vision or examination of the fundus, core vitrectomy for clearing inflammatory debris is a good adjunct to cataract surgery.
- Membranectomy/vitrectomy for cyclitic membranes may be performed to prevent phthisis resulting from prolonged hypotony.
Consultations
A team approach to management of patients with severe, chronic disease requiring systemic immunomodulatory treatment is recommended.
- Ocular immunology and uveitis specialist
- Pediatric rheumatologist
- Child psychiatrist
Medication
The treatment of JIA-associated uveitis is a step-wise progression beginning with topical steroids and mydriatics, progressing to regional steroids, systemic NSAIDs, systemic steroids, immunosuppressive agents, and biologics.
Corticosteroids
These agents decrease inflammation. When considered, corticosteroid treatment often is initiated only after consultation with an ophthalmologist. However, long-term systemic therapy results in an unfavorable visual prognosis.
Prednisolone acetate (Pred Mild, Pred Forte, Econopred)
Strongest steroid of its group and best choice for uveitis. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
1 gtt to affected eye q1-6h
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
A rise in the intraocular pressure may occur; cataract formation may occur with long-term use
Triamcinolone acetonide (Kenalog)
Periocular injections of corticosteroids reserved for patients with more severe disease, or those with posterior segment (eg, vitreous) inflammation. Also used in patients at high risk for CME.
Adult
0.5-1 cc of triamcinolone acetonide 40 mg/cc (as anterior sub-Tenon or transseptal injections)
Pediatric
Administer as in adults
Coadministration with barbiturates, phenytoin, and rifampin decreases effects of triamcinolone
Documented hypersensitivity; fungal, viral, and bacterial skin infections; history of elevated intraocular pressure or glaucoma
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Multiple complications (eg, severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression) may occur; abrupt discontinuation of glucocorticoids may cause adrenal crisis
Prednisone (Deltasone)
May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult
5-60 mg/d PO qd or divided bid/qid; taper over 2 wk, as symptoms resolve
Pediatric
4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk, as symptoms resolve
Corticosteroids may decrease I 131 uptake and produce false-negative results in the nitroblue tetrazolium test for systemic bacterial infection; coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Because complications of treatment with corticosteroids are dependent on size of dose and duration of treatment, make a risk/benefit decision as to dose and duration of treatment and as to whether daily or intermittent therapy should be used; use lowest possible corticosteroid dose to control condition under treatment; psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations; existing emotional instability or psychotic tendencies may be aggravated by corticosteroids; avascular or aseptic necrosis of femoral head has been associated with long-term corticosteroid treatment (also has occurred in high dose, short-term therapy); adverse effect is more likely to occur in predisposing illness such as rheumatoid arthritis or systemic lupus erythematosus
Enhanced effect of corticosteroids occurs in persons with hypothyroidism and cirrhosis; aspirin and NSAIDs should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia; patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly-acting corticosteroids before, during, and after stressful situation is indicated; restrict use of corticosteroids in active tuberculosis to cases of fulminating disseminated tuberculosis in which corticosteroid is used for management of the disease in conjunction with appropriate antituberculous regimen; if corticosteroids are indicated in latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur (during prolonged corticosteroid therapy, these patients should receive chemoprophylaxis); may mask some signs of infection, and new infections may appear during use; there may be decreased resistance and inability to localize infection when corticosteroids are used; if corticosteroids have to be used in presence of bacterial infections, institute appropriate anti-infective therapy
Patients exposed to certain infections (eg, measles, chickenpox) should seek medical advice; corticosteroids may activate latent amebiasis; rule out amebiasis before giving corticosteroids to a patient who has spent time in the tropics or has unexplained diarrhea
Cycloplegics
These agents block nerve impulses to the pupillary sphincter and ciliary muscles, easing pain and photophobia.
Cyclopentolate 0.5-2% (Cyclogyl)
Induces cycloplegia in 25-75 min and mydriasis in 30-60 min. These effects last up to 1 d; however, the duration may be less in the setting of a severe anterior chamber reaction. For this reason, cyclopentolate is less attractive for treating uveitis than homatropine.
Adult
1 gtt to affected eye tid
Pediatric
Administer as in adults
Decreases effects of carbachol and cholinesterase inhibitors
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients (eg, elderly patients) where increased intraocular pressure may be present; can cause toxic anticholinergic systemic adverse effects (common in children especially infants) but incidence rare when used sparingly; compressing lacrimal sac by digital pressure for 1-3 min following instillation may minimize systemic absorption
Homatropine hydrobromide 2-5% (Isopto)
Induces cycloplegia in 30-90 min and mydriasis in 10-30 min. Useful in treating pain from ciliary spasm and decreasing formation of synechiae. These effects last 10-48 h for cycloplegia and 6 h to 4 d for mydriasis, but the duration may be less in the setting of a severe anterior chamber reaction. Homatropine is the preferred agent of choice for uveitis.
Adult
1 gtt to affected eye tid
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in elderly patients where increased intraocular pressure may be present; toxic anticholinergic systemic adverse effects can occur but are rare when used sparingly; adverse effects are more common in children, especially infants; compressing lacrimal sac by digital pressure for 1-3 min following instillation minimizes systemic absorption
Nonsteroidal anti-inflammatory drugs
NSAIDs reduce pain and inflammation and allow for improvements in mobility and function. Used to reduce effect of diffusing prostaglandins on retinal microvasculature and, hence, used in patients at high risk for the development of CME. There are several NSAIDs; however, no single agent exists that is superior to another. Naproxen is used commonly in children.
Indomethacin (Indocin)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Adult
25 mg PO bid/tid; increase daily dose by 25 mg or 50 mg, if required by continuing symptoms, at weekly intervals until satisfactory response is obtained or until total daily dose of 150-200 mg is reached; doses above this amount generally do not increase the effectiveness of the drug
Pediatric
<14 years: Not recommended
If indomethacin treatment is instituted, suggested starting dose is 2 mg/kg/d given in divided doses; maximum daily dosage not to exceed 4 mg/kg/d or 150-200 mg/d, whichever is less
>14 years: Administer as in adults, maximum daily dosage not to exceed 4 mg/kg/d or 150-200 mg/d, whichever is less
Probenecid may increase toxicity of NSAIDs; may decrease natriuretic effect of loop diuretics; coadministration with anticoagulants may prolong PT (watch for signs of bleeding); NSAIDs may increase serum lithium levels and risk of methotrexate toxicity (eg, stomatitis, bone marrow suppression, nephrotoxicity); may increase the serum concentration and prolong the half-life of digoxin
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy; caution in patients with preexisting asthma
Naproxen (Anaprox, Naprelan, Naprosyn)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Adult
500 mg PO, followed by 250 mg q6-8h; not to exceed 1.25 g/d
Pediatric
<2 years: Not established
> 2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d
Probenecid may increase toxicity of NSAIDs; may decrease natriuretic effect of loop diuretics; coadministration with anticoagulants may prolong PT (watch for signs of bleeding); NSAIDs may increase serum lithium levels and risk of methotrexate toxicity (eg, stomatitis, bone marrow suppression, nephrotoxicity)
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion, risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrant further evaluation and may require discontinuation of drug
Ibuprofen (Ibuprin, Advil, Motrin)
For relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult
200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d
Pediatric
Administer as in adults
May decrease effects of loop diuretics with coadministration; coadministration with anticoagulants may increase PT (monitor and watch for signs of bleeding); may increase serum lithium levels and risk of methotrexate toxicity; probenecid may increase toxicity of NSAIDs
Documented hypersensitivity to ibuprofen, other NSAIDs, or aspirin; avoid in peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, and high risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
Ketorolac (Acular)
Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors.
Adult
1 gtt to affected eye bid/qid
Pediatric
Administer as in adults
Additive effect with systemic NSAIDs may occur
Documented hypersensitivity; avoid during pregnancy
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Corneal thinning may occur; category D in third trimester of pregnancy
Diclofenac (Voltaren)
Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which, in turn, decreases formation of prostaglandin precursors. May facilitate outflow of aqueous humor and decreases vascular permeability.
Adult
1 gtt to affected eye bid/qid
Pediatric
Administer as in adults
Additive effect with systemic NSAIDs may occur
Documented hypersensitivity; avoid during pregnancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Corneal thinning may occur
Immunosuppressives (systemic)
These are second-line agents that ameliorate the disease process. Most frequently they are used in combination with first-line agents. They include methotrexate, cyclosporin A, cyclophosphamide, and chlorambucil.
Etanercept (Enbrel)
Binds specifically to tumor necrosis factor (TNF) and blocks its interaction with cell-surface TNF receptor. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.
Adult
50 mg/wk given as two 25-mg subcutaneous injections at separate sites; dose should be administered as two 25-mg injections given either on the same day or 3-4 days apart; doses higher than 50 mg/wk not recommended
Pediatric
<4 years: Not established
4-17 years: 0.8 mg/kg/wk (not to exceed 50 mg/wk); maximum dose that should be administered at a single injection site is 25 mg (1 mL)
>17 years: Administer as in adults
Concurrent administration with anakinra (IL-1 receptor antagonist) has been associated with increased risk of serious infections, increased risk of neutropenia, and no additional benefits compared with these medicinal products alone
Documented hypersensitivity; patients with sepsis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with congestive heart failure; if patient develops symptoms suggestive of a lupuslike syndrome following treatment with etanercept, discontinue treatment and carefully evaluate patient
Methotrexate (Folex PFS)
Folic acid analog, decreases inflammation, and has steroid-sparing effect. Useful in JIA-associated uveitis, where may reduce inflammation in patients who do not respond adequately to steroid treatment.
Adult
For inflammatory eye disease: 7.5-25 mg/wk PO once per week in a single undivided dose
Pediatric
For inflammatory eye disease: 10-25 mg/m2 PO once weekly
For organ transplantation: Not established
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX
Coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels
Probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; may increase plasma levels of thiopurines
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor CBC monthly, and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); MTX has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems
Discontinue if significant drop in blood counts occurs; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX but may increase potential for toxicity
Cyclosporine (Sandimmune)
Potent immunosuppressive agent with narrow therapeutic range. Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease) for a variety of organs.
Adult
For inflammatory eye disease: 2-5 mg/kg/d PO divided bid
For organ transplantation: 5-15 mg/kg/d PO qd or divided bid or 2-10 mg/kg/d IV divided q8-12h
Pediatric
Not established
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis since it may increase risk of cancer; abnormal renal function; uncontrolled infection; primary or secondary immunodeficiency excluding autoimmune disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause increases in serum creatinine and urea levels, even at recommended doses as a result of reduced glomerular filtration rate (GFR); functional changes are dose dependent and reversible, and usually respond to dose reduction; although less frequent, some patients may develop structural changes in kidney (eg, interstitial fibrosis) during long-term treatment; although these renal changes are less common, they may be irreversible; in renal transplant patients, structural changes in kidney must be differentiated from organ rejection; close monitoring of parameters that assess renal function is required; abnormal values may necessitate dose reduction; in patients who are treated with cyclosporine for nontransplant indications, risk of renal structural changes is greater if serum creatinine level increases more than 30% from the patient's own baseline value; regular measurements of serum creatinine levels must be made
Cyclophosphamide (Cytoxan, Neosar)
Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult
For inflammatory eye disease: 1-3 mg/kg/d PO or 500-750 mg/m2 IV every month
Pediatric
Administer as in adults
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects of cyclophosphamide; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones
Chloramphenicol may increase half-life of cyclophosphamide while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Administer cautiously to patients with any of the following conditions: leukopenia, thrombocytopenia, tumor cell infiltration of bone marrow, previous radiation therapy, previous therapy with other cytotoxic agents, or impaired hepatic or renal function; because may exert a suppressive action in immune mechanisms, consider interruption or modification of dosage for patients who develop bacterial, fungal, or viral infections; this is especially true for patients receiving concomitant steroid therapy and perhaps those with recent history of steroid therapy because infections in some of these patients have been fatal; varicella-zoster infections appear to be particularly dangerous under these circumstances; monitor renal function in patients being considered as candidates for long-term therapy; examine urine regularly for red cells that may precede hemorrhagic cystitis
Chlorambucil (Leukeran)
Aromatic nitrogen mustard derivative that acts as bifunctional alkylating agent. Alkylation takes place through formation of highly reactive ethylenimonium radical. Probable mode of action involves cross-linkage of the ethylenimonium derivative between 2 strands of helical DNA and subsequent interference with replication.
Adult
For inflammatory eye disease: 0.1-0.2 mg/kg/d PO or 3-6 mg/m2/d PO for 3-6 wk and adjust dose depending on blood counts
Pediatric
0.1-0.2 mg/kg PO qd for 5-15 wk
None reported
Should not be administered to patients who are resistant to the drug or who have developed hypersensitivity to it; should not be used within 4 wk of a full course of radiation or chemotherapy
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor blood counts once or twice weekly in patients under treatment; at therapeutic dosage, chlorambucil depresses lymphocytes and has less effect on neutrophil and platelet counts and on hemoglobin levels; discontinuation of chlorambucil is not necessary at first sign of a fall in neutrophils but the decrease may continue for 10 d or more after the last dose; when lymphocytic infiltration of the bone marrow is present, or bone marrow is hypoplastic, daily dose should not exceed 0.1 mg/kg body weight; carefully monitor patients with evidence of impaired renal function because they are prone to additional myelosuppression associated with azotemia
Metabolism of chlorambucil is still under investigation, consider dose reduction in gross hepatic dysfunction; since other alkylating agents (eg, cyclophosphamide) inhibit serum cholinesterase, patients receiving chlorambucil may exhibit increased sensitivity to neuromuscular blocking agents (eg, succinylcholine); to avoid risk of prolonged apnea, the dose of succinylcholine should be reduced when administered concomitantly with chlorambucil; like other cytotoxic drugs, chlorambucil may induce hyperuricemia secondary to rapid lysis of neoplastic cells; monitor patient's blood uric acid level and take necessary supportive and pharmacological measures to control the problem
Has been shown to cause chromatid or chromosome damage in humans; development of acute leukemia after chlorambucil therapy for chronic lymphocytic leukemia has been reported (not clear whether acute leukemia was part of natural history of disease or if chemotherapy was the cause); a comparison of patients with ovarian cancer who received alkylating agents with those who did not, showed that the use of alkylating agents including chlorambucil, significantly increased the incidence of acute leukemia; acute myelogenous leukemia has been reported in a small proportion of patients receiving chlorambucil as long-term adjuvant therapy for breast cancer; leukemogenic risk must be balanced
against potential therapeutic benefit when considering the use of chlorambucil
May cause suppression of ovarian function and amenorrhea has been reported following chlorambucil therapy; azoospermia has been observed as a result of therapy (a total dose of at least 400 mg is necessary); varying degrees of recovery of spermatogenesis has been reported in patients with lymphoma following treatment with chlorambucil in total doses of 410-2600 mg; as with other cytotoxic agents, chlorambucil is potentially teratogenic
Tumor necrosis factor (TNF) inhibitors
TNF is a cytokine of which 2 forms have been identified with similar biological properties. TNF-alpha or cachectin is produced predominantly by macrophages, and TNF-beta or lymphotoxin is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that may contribute to symptoms.
Adalimumab (Humira)
Recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). Indicated to reduce inflammation and inhibit progression of structural damage in moderate-to-severe rheumatoid arthritis. Reserved for those who experience inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). Can be used alone or in combination with methotrexate (MTX) or other DMARDs. Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors. In 2008, adalimumab was approved by the FDA for juvenile idiopathic arthritis.
Adult
40 mg SC q2wk; may increase to 40 mg SC qwk in some patients not taking concomitant MTX
Pediatric
<4 years: Not established
4-17 years:
15-29 kg: 20 mg SC q2wk
>29 kg: 40 mg SC q2wk
May interfere with immune response to live virus vaccine (eg, MMR) and reduce efficacy; methotrexate (MTX) decreases clearance (available data do not support adjusting dose of either adalimumab or MTX); coadministration with anakinra (an interleukin-1 antagonist that also blocks TNF) may cause additive adverse effects, particularly development of serious infections
Documented hypersensitivity; active infection
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Causes immunosuppression; may be associated with serious infections (some fatal), including reactivation of tuberculosis, sepsis, or opportunistic infections; increases risk for lymphoma development; associated with CNS demyelination (rare); discontinue if serious infection develops; autoantibody development may occur causing lupus-like syndrome; may cause hypersensitivity reactions, including anaphylaxis and hematologic adverse effects (ie, pancytopenia, aplastic anemia); exacerbation of CHF or new onset CHF has been observed with TNF-blocking agents
Infliximab (Remicade)
Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Reduces infiltration of inflammatory cells and TNF-alpha production in inflamed areas. Used with methotrexate in patients who have had inadequate response to methotrexate monotherapy.
Adult
3 mg/kg IV (in combination with methotrexate therapy); follow by additional 3 mg/kg at 2 wk and 6 wk after first dose; repeat q8wk thereafter
Pediatric
Not established; various trials have added infliximab to existing therapy in children with JIA; typical investigational dose is 3 mg/kg IV at weeks 0, 2, and 6, and then q8wk
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; more cases of lymphoma were observed in TNF alpha-blockers compared to controlled groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections
Immunomodulator
Abatacept decreases inflammation by blocking T-cell activation.
Abatacept (Orencia)
Selective co-stimulation modulator that inhibits T-cell activation by binding to CD80 and CED86, thereby blocking CD28 interaction. CD28 interaction provides a signal needed for full T-cell activation that is implicated in RA pathogenesis. Indicated for reducing signs and symptoms of RA, slowing progression of structural damage and improving physical function in adults with moderate-to-severe RA who have inadequate response to DMARDs, methotrexate, or TNF antagonists. May be used as monotherapy or with DMARDs (other than TNF antagonists, because of increased risk of serious infections [4.4% vs 0.8%]). Not recommended for concomitant use with anakinra (insufficient experience).
Adult
Rheumatoid arthritis: Dose according to body weight; after initial administration, repeat at 2 wk and 4 wk after first infusion, then q4wk; infuse over 30 min
<60 kg: 500 mg IV
60-100 kg: 750 mg IV
>100 kg: 1 g IV
Pediatric
<6 years: Not established
Juvenile idiopathic arthritis: Dose according to body weight; administer on days 1, 15, and 29, then q4wk thereafter; infuse IV over 30 min
6-17 years:
<75 kg: 10 mg/kg IV
75-100 kg: 750 mg IV
>100 kg: 1 g IV
In clinical trials, coadministration with TNF antagonists resulted in increased risk of serious infections; do not administer concurrently with live virus vaccines (eg, MMR) or within 3 mo of discontinuation
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue if serious infection occurs; patients with COPD developed adverse effects more frequently, including COPD exacerbations, cough, rhonchi, and dyspnea; serious adverse reactions include serious infections (3% vs 1.9% placebo); malignancy frequency was similar to that of placebo (1.3% vs 1.1% placebo), with the exception of lung cancer (0.2% vs 0% placebo); common adverse effects include headache, upper respiratory tract infection, nasopharyngitis, and nausea
More on Uveitis, Juvenile Idiopathic Arthritis |
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| Differential Diagnoses & Workup: Uveitis, Juvenile Idiopathic Arthritis |
 Treatment & Medication: Uveitis, Juvenile Idiopathic Arthritis |
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Further Reading
Keywords
uveitis, juvenile idiopathic arthritis, juvenile idiopathic arthritis associated uveitis, JIA-associated uveitis, JIA uveitis, JRA-associated uveitis, JRA uveitis, juvenile rheumatoid arthritis, juvenile rheumatoid arthritis associated uveitis, vision loss, blindness, chronic iridocyclitis, chronic intraocular inflammation
