Adalimumab

Adalimumab is a an Antirheumatic Agent belonging to pharmacology class of Monoclonal Antibody

Adalimumab can be used in the treatment of Crohn disease, Hidradenitis suppurativa, moderate to severe, refractory, Juvenile idiopathic arthritis (Adalimumab and adalimumab biosimilars), Plaque psoriasis, Rheumatoid arthritis, Spondyloarthritis , Uveitis, non-infectious.It is also used to treat Sarcoidosis, refractory

It is slowly get absorbed following SC administration. Absolute bioavailability: 64%. Time to peak plasma concentration: Approx 3-8 days and crosses the placenta and enters breast milk. Concentrated in the synovial fluid (31-96% of serum) with volume of distribution: 4.7-6 L with Terminal elimination half-life of approx 2 weeks (range: 10-20 days).

The common side effects associated with Adalimumab include Gastrointestinal/diverticular perforation, haematologic effects (e.g. neutropenia, thrombocytopenia), increased hepatic transaminases, total cholesterol, triglycerides.

Adalimumab is available in the form of Injection, prefilled glass syringes.

The molecule is available in India, USA, Japan, Germany.

Adalimumab belonging to the Monoclonal Antibody acts a Antirheumatic Agent.

Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), preventing it from connecting to TNF receptor sites and preventing the inflammatory processes that are subsequently triggered by cytokines. In immune-mediated arthritis, pathologic pain and joint deterioration are caused by increased TNF levels in the synovial fluid. Psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis symptoms are reduced with adalimumab. It slows down the growth of rheumatoid and psoriatic arthritis' structural damage. decreases signs and symptoms and keeps ulcerative colitis and Crohn's disease in clinical remission; decreases plaque psoriasis epidermal thickness and inflammatory cell infiltration.

Adalimumab is available in Injection, prefilled glass syringe

IV : Allow diluted solution for infusion to reach room temperature prior to administration; infuse over 60 minutes using a dedicated IV line. Do not infuse other agents through same IV line. Do not administer IV push or IV bolus. If additional doses are necessary for the management of cytokine-release syndrome, the interval between doses should be at least 8 hours. Do not use if opaque particles or discoloration is visible.

Adalimumab can be used in the treatment of Crohn disease, Hidradenitis suppurativa, moderate to severe, refractory, Juvenile idiopathic arthritis (Adalimumab and adalimumab biosimilars), Plaque psoriasis, Rheumatoid arthritis, Spondyloarthritis , Uveitis, non-infectious. It is also used to treat Sarcoidosis, refractory.

Human immunoglobulin G1 (IgG1) monoclonal antibody adalimumab is made from recombinant DNA. It specifically binds to human tumour necrosis factor- (TNF-) and prevents its interaction with p55 and p75 cell surface TNF receptors, preventing cytokine-driven inflammatory processes.

Adalimumab is approved for use in the following clinical indications

Crohn disease, moderate to severe, induction and maintenance of remission (Adalimumab and adalimumab biosimilars): Treatment of moderately to severely active Crohn disease in adults and pediatric patients ≥6 years of age.

Hidradenitis suppurativa, moderate to severe, refractory: Treatment of moderate to severe hidradenitis suppurativa in adults (Adalimumab and adalimumab biosimilars) and pediatric patients ≥12 years of age (Adalimumab only).

Juvenile idiopathic arthritis (Adalimumab and adalimumab biosimilars): Treatment (to reduce signs/symptoms) of active polyarticular juvenile idiopathic arthritis (moderate to severe) in pediatric patients ≥2 years of age; may be used alone or in combination with methotrexate.

Plaque psoriasis, moderate to severe (Adalimumab and adalimumab biosimilars): Treatment of chronic plaque psoriasis (moderate to severe) in adults who are candidates for systemic therapy or phototherapy, and when other systemic therapies are less appropriate (with close monitoring and regular follow-up).

Rheumatoid arthritis (Adalimumab and adalimumab biosimilars): Treatment (to reduce signs/symptoms, induce major clinical response, inhibit progression of structural damage, and improve physical function) of active rheumatoid arthritis (moderate to severe) in adults; may be used alone or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).

Spondyloarthritis (Adalimumab and adalimumab biosimilars):

Axial spondyloarthritis (eg, ankylosing spondylitis): Treatment (to reduce signs/symptoms) of active ankylosing spondylitis in adults. May also be used off label for nonradiographic axial spondyloarthritis

Psoriatic arthritis: Treatment (to reduce signs/symptoms, inhibit progression of structural damage, and improve physical function) of psoriatic arthritis (a form of peripheral spondyloarthritis) in adults; may be used alone or in combination with nonbiologic DMARDs. May also be used off label for nonpsoriatic peripheral spondyloarthritis (eg, reactive arthritis, arthritis associated with inflammatory bowel disease).

Ulcerative colitis, moderate to severe, induction and maintenance of remission: Treatment of moderately to severely active ulcerative colitis in adults (Adalimumab and adalimumab biosimilars) and pediatric patients ≥5 years of age (Adalimumab only). Note: Efficacy in patients intolerant of or no longer responsive to other tumor necrosis factor blockers has not been established.

Uveitis, noninfectious (Adalimumab only): Treatment of noninfectious intermediate, posterior, and panuveitis in adults and children ≥2 years of age.

Although not approved there have been certain off labelled uses documented for toclizumab which include:

Axial spondyloarthritis, including ankylosing spondylitis (Adalimumab and adalimumab biosimilars):

Note: Reserve for patients who do not have an adequate response to nonsteroidal anti-inflammatory drugs; may continue NSAIDs and/or analgesics .

SUBQ: 40 mg every other week.

Crohn disease, moderate to severe, induction and maintenance of remission (Adalimumab and adalimumab biosimilars):

Note: Combination therapy with an immunomodulator (ie, thiopurine or methotrexate) is generally preferred .

Initial: SUBQ: 160 mg (given over 1 or 2 days), then 80 mg 2 weeks later (day 15)

Note: If switching from another anti-tumor necrosis factor agent, may use this induction regimen.

Maintenance: SUBQ: 40 mg every other week beginning day 29.

Hidradenitis suppurativa, moderate to severe, refractory (Adalimumab and adalimumab biosimilars):

Initial: SUBQ: 160 mg (given over 1 or 2 days), then 80 mg 2 weeks later (day 15).

Maintenance: SUBQ: 40 mg every week beginning day 29 or 80 mg every other week beginning day 29 .

Note: 40 mg every week regimen has been more extensively studied and is therefore preferred by some experts.

Nonradiographic axial spondyloarthritis (off-label use):

Note: Reserve for patients who do not have an adequate response to NSAIDs; may continue NSAIDs and/or analgesics.

SUBQ: 40 mg every other week.

Peripheral spondyloarthritis, nonpsoriatic (off-label use):

Note: May continue methotrexate, other nonbiologic DMARDs, corticosteroids, NSAIDs, and/or analgesics .

SUBQ: 40 mg every other week.

Plaque psoriasis, moderate to severe (Adalimumab and adalimumab biosimilars):

Note: Generally used as systemic monotherapy; may continue adjuvant topical therapies (eg, emollients, corticosteroids) as needed. A clinician experienced with use of adalimumab for plaque psoriasis should be involved in treatment.

Initial: SUBQ: 80 mg as a single dose.

Maintenance: SUBQ: 40 mg every other week beginning 1 week after initial dose. Note: Some patients may require 40 mg every week.

Psoriatic arthritis (Adalimumab and adalimumab biosimilars):

Note: May continue methotrexate, other nonbiologic DMARDs, corticosteroids, NSAIDs, and/or analgesics.

SUBQ: 40 mg every other week.

Rheumatoid arthritis (Adalimumab and adalimumab biosimilars):

Note: For use as an alternative to methotrexate in disease-modifying antirheumatic drug (DMARD)–naive patients with moderate to high disease activity, or as adjunctive therapy in patients who have not met treatment goals despite maximally tolerated methotrexate therapy. May use in combination with other nonbiologic DMARDs, glucocorticoids, NSAIDs, and/or analgesics. A clinician experienced with use of adalimumab for rheumatoid arthritis should be involved in treatment.

SUBQ: Initial: 40 mg every other week; for select patients with an inadequate response, may increase dose to 40 mg every week or 80 mg every other week.

Sarcoidosis, refractory (adjunctive agent) (off-label use):

Note: For use as an adjunctive agent in patients in whom treatment goals have not been met despite glucocorticoids and other immunosuppressants (eg, methotrexate) .A clinician experienced with use of adalimumab should be involved in treatment.

Initial: SUBQ: The optimal dosing strategy is not known; one example of an initial regimen is 40 to 120 mg on week 0, 40 to 80 mg on week 1, and 40 mg on week 2.

Maintenance: SUBQ: 40 mg every 1 to 2 weeks. The optimal frequency and duration of therapy are not known and must be individualized based on response; after a stable response is achieved (eg, after 6 months), one option is to gradually prolong the dosing interval (eg, to every 2 weeks) and discontinue after 3 months if response remains adequate.

Ulcerative colitis, moderate to severe, induction and maintenance of remission (Adalimumab and adalimumab biosimilars):

Initial: SUBQ: 160 mg (given over 1 or 2 days), then 80 mg 2 weeks later (day 15).

Maintenance: SUBQ: 40 mg every other week beginning day 29. If a disease flare occurs, some experts increase to 40 mg every week . Note: Only continue maintenance treatment in patients demonstrating clinical remission by 8 weeks (day 57) of therapy.

Uveitis, noninfectious (Adalimumab only):

Note: Generally reserved for patients with an incomplete response to first-line agents and ≥1 other systemic therapies.

Initial: SUBQ: 80 mg as a single dose.

Maintenance: SUBQ: 40 mg every other week beginning 1 week after initial dose.

• Injection, prefilled glass syringe: 10mg/0.1mL, 10mg/0.2mL , 20mg/0.2mL, 20mg/0.4mL, 40mg/0.4mL, 40mg/0.8mL, 80mg/0.8mL

Injection, prefilled glass syringe

• Dose Adjustment in Kidney impairment patient:

Altered kidney function: SUBQ : No dosage adjustment necessary for any degree of kidney dysfunction (Ref).

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m 2 ): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients: SUBQ : No dosage adjustment necessary.

Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed: SUBQ : No dosage adjustment or supplemental dose necessary; patients with end-stage kidney disease (ESKD) often suffer from impaired immune function, monitor closely for infection during adalimumab therapy.

Peritoneal dialysis: Unlikely to be significantly dialyzed (expert opinion): SUBQ : No dosage adjustment necessary; patients with ESKD often suffer from impaired immune function; monitor closely for infection during adalimumab therapy.

CRRT: SUBQ : No dosage adjustment necessary.

PIRRT (eg, sustained, low-efficiency diafiltration): SUBQ : No dosage adjustment necessary.

• Dose Adjustment in Pediatric Patient:

Crohn disease, moderate to severe:

Children ≥6 years and Adolescents:

17 kg to <40 kg: SUBQ:

Initial: 80 mg on day 1, then 40 mg administered 2 weeks later (day 15).

Maintenance (beginning day 29): 20 mg every other week. Patients who continue to experience flares after 12 weeks of therapy may benefit from weekly dosing.

≥40 kg: SUBQ:

Initial: 160 mg (administered on day 1 or split and administered over 2 consecutive days), then 80 mg administered 2 weeks later (day 15).

Maintenance (beginning day 29): 40 mg every other week. Weekly dosing should be considered for patients with loss of response or low trough concentrations (<7.5 mcg/mL).

Hidradenitis suppurativa:

Children ≥12 years and Adolescents:

30 to <60 kg: SUBQ:

Initial: 80 mg on day 1.

Maintenance (beginning day 8): 40 mg every other week.

≥60 kg: SUBQ:

Initial: 160 mg (administered as full dose on day 1 or dose split and administered over 2 consecutive days), then 80 mg 2 weeks later (day 15).

Maintenance (beginning day 29): 40 mg weekly or 80 mg every other week.

Juvenile idiopathic arthritis (JIA):

Fixed dosing:

Children ≥2 years and Adolescents:

10 kg to <15 kg: SUBQ: 10 mg every other week.

15 to <30 kg: SUBQ: 20 mg every other week.

≥30 kg: SUBQ: 40 mg every other week.

BSA-directed dosing: Note: Dosing based on trials performed with Adalimumab product.

Children 2 to <4 years: SUBQ: 24 mg/m²/dose every other week; maximum dose: 20 mg/dose .

Children and Adolescents 4 to 17 years: SUBQ: 24 mg/m²/dose every other week; maximum dose: 40 mg/dose.

Ulcerative colitis; moderate to severe:

Fixed dosing: Children ≥5 years and Adolescents:

20 to <40 kg: SUBQ:

Initial: 80 mg on day 1, then 40 mg administered weekly for 2 weeks (a dose on day 8 and day 15).

Maintenance (beginning day 29): 40 mg every other week or 20 mg every week.

≥40 kg: SUBQ:

Initial: 160 mg on day 1 (administered as full dose on day 1 or dose split and administered over 2 consecutive days), then 80 mg administered weekly for 2 weeks (a dose on day 8 and day 15).

Maintenance (beginning day 29): 80 mg every other week or 40 mg every week.

BSA-directed dosing: Children and Adolescents: SUBQ: Initial: 92 mg/m² (maximum dose: 160 mg/dose), then 46 mg/m² (maximum dose: 80 mg/dose) 2 weeks later, then on day 29, begin maintenance therapy: 23 mg/m² every other week (maximum dose: 40 mg/dose). Note: Trials performed with Adalimumab product.

Uveitis (noninfectious intermediate, posterior, and panuveitis):

Fixed dosing: Children ≥2 years and Adolescents:

10 kg to <15 kg: SUBQ: 10 mg every other week.

15 to <30 kg: SUBQ: 20 mg every other week.

≥30 kg: SUBQ: 40 mg every other week.

BSA-directed dosing: Children ≥4 years and Adolescents: SUBQ: 24 or 40 mg/m²/dose every 2 weeks; maximum dose 40 mg/dose (Ref). Dosing based on one prospective trial comparing 24 mg/m²/dose every 2 weeks of adalimumab (n=16, ages 6 to 12 years) to infliximab (n=17, ages 5 to 13 years) and on a retrospective trial of biologic response modifiers, including 5 patients who received adalimumab at 40 mg/m²/dose every 2 weeks. Note: Trials performed with Adalimumab product.

The dietary restriction should be individualized as per patient requirements.

Adalimumab may be contraindicated in the following conditions:

Hypersensitivity to E. coli-derived proteins or Adalimumab . Neutropenia (absolute neutrophil count <1.5 x 10⁹/L). Severe renal impairment (CrCl <30 mL/min).

The treating physician must closely monitor the patient and keep pharmacovigilance as follows

Concerns related to adverse effects:

• Antibody formation: Formation of neutralizing anti-drug antibodies may occur with biologic tumor necrosis factor (TNF) inhibitors and may be associated with loss of efficacy.

• Hematologic disorders: Rare cases of pancytopenia and aplastic anemia have been reported with TNF-blockers. Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias; discontinue if significant hematologic abnormalities are confirmed. Use with caution in patients with a history of significant hematologic abnormalities.

Disease-related concerns:

• Active infection: Do not initiate therapy in patients with an active infection, including clinically important localized infection.

• HIV: Use with caution in HIV-positive patients; TNF-α inhibitors may be appropriate in patients receiving highly active antiretroviral therapy, provided they have normal CD4 counts, no viral load, and no recent opportunistic infections.

There is no sufficient scientific evidence traceable regarding use and safety of Adalimumab in concurrent use with alcohol.

There is no sufficient scientific evidence traceable regarding use and safety of Adalimumab in concurrent use with any particular food.

Not assigned.

Risk Summary: Studies report a rate of 5.6% for major birth defects with first trimester use of this drug in pregnant women with rheumatoid arthritis (RA), and a rate of 7.8% and 5.5% for major birth defects in the disease-matched and non-diseased comparison groups.

There is no sufficient scientific evidence traceable regarding use and safety of Adalimumab in concurrent use with any particular food.

The adverse reactions related to Adalimumab can be categorized as

Common Adverse effects: Gastrointestinal/diverticular perforation, hematologic effects (e.g. neutropenia, thrombocytopenia), increased hepatic transaminases, total cholesterol, triglycerides

Less Common Adverse effects: Constipation, diarrhea, nausea, abdominal pain, mouth ulceration, gastritis.

Rare Adverse effects: Cough, dyspnea, nasopharyngitis.

The clinically relevant drug interactions of Adalimumab is briefly summarized here

May reduce the serum concentrations of warfarin, theophylline and ciclosporin.

Potentially Fatal: May increase the risk of vaccine-associated infections with live vaccines. Increased risk of serious infections with other biologic DMARDs (e.g. anakinra, abatacept, rituximab) and other TNF-α antagonists or immunosuppressants (e.g. corticosteroids, methotrexate).

The common side of Adalimumab include the following

Gastrointestinal/diverticular perforation, hematologic effects (e.g. neutropenia, thrombocytopenia), increased hepatic transaminases, total cholesterol, triglycerides.

Pregnancy

Risk Summary

Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Adalimumab Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn’s disease (CD). Registry results showed a rate of 10% for major birth defects with first-trimester use of adalimumab in pregnant women with RA or CD and a rate of 7.5% for major birth defects in the disease matched comparison cohort. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in-utero exposed infant (see Clinical Considerations). In an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with intravenous administration of adalimumab during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (MRHD) of 40 mg subcutaneous without methotrexate. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The U.S. general population's estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and embryo/fetal risk

Published data suggest that the risk of adverse pregnancy outcomes in women with RA or inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

Fetal/Neonatal Adverse Reactions

Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester (see Data). Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to Adalimumab in utero.

Data

Human Data

A prospective cohort pregnancy exposure registry conducted by OTIS/MotherToBaby in the U.S. and Canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 RA, 152 CD) treated with adalimumab during the first trimester and 106 women (74 RA, 32 CD) not treated with adalimumab. The proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% RA, 10.5% CD) and 7.5% (6.8% RA, 9.4% CD), respectively. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. This study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design. In an independent clinical study conducted in ten pregnant women with IBD treated with Adalimumab, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. The last dose of Adalimumab was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16-19.7 µg/mL in cord blood, 4.28-17.7 µg/mL in infant serum, and 0-16.1 µg/mL in maternal serum. In all but one case, the cord blood level of adalimumab was higher than the maternal serum level, suggesting adalimumab actively crosses the placenta. In addition, one infant had serum levels at each of the following: 6 weeks (1.94 µg/mL), 7 weeks (1.31 µg/mL), 8 weeks (0.93 µg/mL), and 11 weeks (0.53 µg/mL), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth.

Animal Data

In an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the MRHD without methotrexate (on an AUC basis with maternal IV doses up to 100 mg/kg/week). Adalimumab did not elicit harm to the fetuses or malformations

Lactation

Risk Summary

Limited data from case reports in the published literature describe the presence of adalimumab in human milk at infant doses of 0.1% to 1% of the maternal serum level. Published data suggest that the systemic exposure to a breastfed infant is expected to be low because adalimumab is a large molecule and is degraded in the gastrointestinal tract. However, the effects of local exposure in the gastrointestinal tract are unknown. There are no reports of adverse effects of adalimumab on the breastfed infant and no effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Adalimumab and any potential adverse effects on the breastfed child from Adalimumab or from the underlying maternal condition.

Pediatric Use

Safety and efficacy of Adalimumab in pediatric patients for uses other than polyarticular juvenile idiopathic arthritis (JIA), pediatric Crohn’s disease and pediatric uveitis have not been established. Due to its inhibition of TNFα, Adalimumab administered during pregnancy could affect immune response in the in utero-exposed newborn and infant. Data from eight infants exposed to Adalimumab in utero suggest adalimumab crosses the placenta.

The clinical significance of elevated adalimumab levels in infants is unknown. The safety of administering live or live-attenuated vaccines in exposed infants is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. Post-marketing cases of lymphoma, including hepatosplenic T-cell lymphoma and other malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers including Adalimumab

Juvenile Idiopathic Arthritis

In Study JIA-I, Adalimumab was shown to reduce signs and symptoms of active polyarticular JIA in patients 4 to 17 years of age.

Evidence from adequate and well-controlled studies of Adalimumab in adults and a 2:1 randomized, controlled clinical study in 90 pediatric patients. The safety and effectiveness of Adalimumab have not been established in pediatric patients with uveitis less than 2 years of age. Hidradenitis Suppurativa Use of Adalimumab in pediatric patients 12 years of age and older for HS is supported by evidence from adequate and well-controlled studies of Adalimumab in adult HS patients. Additional population pharmacokinetic modeling and simulation predicted that weight-based dosing of Adalimumab in pediatric patients 12 years of age and older can provide generally similar exposure to adult HS patients. The course of HS is sufficiently similar in adult and adolescent patients to allow extrapolation of data from adult to adolescent patients. The recommended dose in pediatric patients 12 years of age or older is based on body weight

The use of Adalimumab has not been established in patients less than 12 years of age with HS. 8.5 Geriatric Use A total of 519 RA patients 65 years of age and older, including 107 patients 75 years of age and older, received Adalimumab in clinical studies RA-I through IV. No overall difference in effectiveness was observed between these patients and younger patients. The frequency of serious infection and malignancy among Adalimumab-treated patients over 65 years of age was higher than for those under 65 years of age. Because there is a higher incidence of infections and malignancies in the elderly population, use caution when treating the elderly.

Doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose-limiting toxicities. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.

Pharmacodynamics:

Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), preventing it from connecting to TNF receptor sites and preventing the inflammatory processes that are subsequently triggered by cytokines. In immune-mediated arthritis, pathologic pain and joint deterioration are caused by increased TNF levels in the synovial fluid. Psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis symptoms are reduced with adalimumab. It slows down the growth of rheumatoid and psoriatic arthritis' structural damage. decreases signs and symptoms and keeps ulcerative colitis and Crohn's disease in clinical remission; decreases plaque psoriasis epidermal thickness and inflammatory cell infiltration.

Pharmacokinetics:

Absorption: Slowly absorbed following SC administration. Absolute bioavailability: 64%. Time to peak plasma concentration: Approx 3-8 days.

Distribution: Crosses the placenta and enters breast milk. Concentrated in the synovial fluid (31-96% of serum). Volume of distribution: 4.7-6 L.

Excretion: Terminal elimination half-life: Approx. 2 weeks (range: 10-20 days).

1. https://www.uptodate.com/contents/Adalimumab -drug-information?search=Adalimumab &source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1#F154338
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022352s017lbl.pdf
3. https://www.medicaid.nv.gov/Downloads/provider/Adalimumab _2015-1215.pdf
4. https://www.mims.com/india/drug/info/Adalimumab ?type=full&mtype=generic#mechanism-of-action