The injectable interleukin (IL)-23 antagonist risankizumab-rzza (Skyrizi – Abbvie), previously approved by the FDA for treatment of Crohn's disease (CD), has now been approved for treatment of moderately to severely active ulcerative colitis (UC) in adults. Risankizumab is the first IL-23 antagonist to be approved for treatment of both CD and UC. It is also approved for treatment of plaque psoriasis and psoriatic arthritis.

The FDA has approved the interleukin (IL)-23 antagonist mirikizumab-mrkz (Omvoh – Lilly) for treatment of moderately to severely active ulcerative colitis (UC) in adults. Mirikizumab is the first selective IL-23 antagonist to be approved for this indication. Ustekinumab (Stelara), an IL-12/23 antagonist, was approved for treatment of UC in 2019. The IL-23 antagonist risankizumab (Skyrizi) is approved for treatment of Crohn's disease.

The FDA has approved ritlecitinib (Litfulo – Pfizer), an oral JAK and TEC kinase family inhibitor, for treatment of severe alopecia areata in patients ≥12 years old. Ritlecitinib is the second oral drug to be approved in the US for treatment of severe alopecia areata; baricitinib (Olumiant), a JAK inhibitor, is approved only for use in adults.

The oral sphingosine 1-phosphate (S1P) receptor modulator etrasimod (Velsipity – Pfizer) has been approved by the FDA for treatment of moderately to severely active ulcerative colitis in adults. It is the second oral S1P receptor modulator to be approved in the US for this indication; ozanimod (Zeposia) was the first.

Ulcerative colitis (UC) and Crohn's disease (CD), referred to collectively as inflammatory bowel disease (IBD), are chronic immune-mediated inflammatory conditions. Guidelines for treatment of UC and CD have been updated in recent years

View the Table: Some Drug Interactions with Drugs for IBD

View the Table: Some Drugs for Inflammatory Bowel Disease

The oral Janus kinase (JAK) inhibitor baricitinib (Olumiant – Lilly), which was previously approved by the FDA for treatment of moderately to severely active rheumatoid arthritis and treatment of COVID-19 in certain hospitalized adults, has now been approved for treatment of severe alopecia areata in adults. Baricitinib is the first systemic treatment to be approved in the US for this indication.

The FDA has approved the oral Janus kinase (JAK) inhibitor upadacitinib (Rinvoq – Abbvie) for treatment of moderately to severely active ulcerative colitis in adults who have had an inadequate response to or cannot tolerate one or more tumor necrosis factor (TNF) inhibitors. Upadacitinib is the second JAK inhibitor to be approved for this indication; tofacitinib (Xeljanz) was the first. Upadacitinib is also approved for treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, and ankylosing spondylitis.

The FDA has approved a 1.5% topical cream formulation of the Janus kinase (JAK) inhibitor ruxolitinib (Opzelura – Incyte) for short-term, non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients ≥12 years old whose disease has not been adequately controlled with other topical prescription drugs. Ruxolitinib is the first JAK inhibitor to be approved for topical use and the first to be approved in the US for treatment of AD. An oral formulation of ruxolitinib (Jakafi) is approved for treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease.

Rheumatoid arthritis (RA) is prevalent in 0.5% of adults in the US; it is about 2.5 times more common in women than in men. Guidelines for treatment of RA from the American College of Rheumatology were recently updated. The goal of treatment is to minimize disease activity and prevent irreversible joint damage.

View Expanded Table: Some Biologic Drugs and JAK Inhibitors for Rheumatoid Arthritis

View the Flowchart: Rheumatoid Arthritis Treatment

The FDA has required updates to the boxed warnings in the labeling of the Janus kinase (JAK) inhibitors tofacitinib (Xeljanz, Xeljanz XR), baricitinib (Olumiant), and upadacitinib (Rinvoq) describing increased risks of major adverse cardiovascular events, malignancy, thrombosis, and death with their use. The new warnings were prompted by the results of a postmarketing safety trial with tofacitinib and were added to the labels of baricitinib and upadacitinib based on the presumption of a class effect. The tofacitinib package insert had contained a boxed warning about an increased risk of thrombosis and mortality with a dosage of 10 mg twice daily since 2019, but the new warnings are not limited by dose.

The oral sphingosine 1-phosphate (S1P) receptor modulator ozanimod (Zeposia – Bristol Myers Squibb) has been approved by the FDA for treatment of adults with moderately to severely active ulcerative colitis. It is the first S1P receptor modulator to be approved for treatment of ulcerative colitis. Ozanimod was approved in March 2020 for use in adults with relapsing forms of multiple sclerosis.

Atopic dermatitis (AD; also known as eczema) is frequently associated with other atopic disorders such as allergic rhinitis, asthma, and food allergy. It commonly presents in infancy and early childhood and has a relapsing course, often improving by adolescence, but sometimes persisting into (or first appearing in) adulthood or even old age.

Psoriatic arthritis is a chronic inflammatory arthropathy associated with psoriasis. A recent review found that about 20% of patients with psoriasis have psoriatic arthritis. Updated guidelines for treatment of psoriatic arthritis have recently been published.

The FDA has approved upadacitinib (Rinvoq – Abbvie), an oral Janus kinase (JAK) inhibitor, for treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to or cannot tolerate methotrexate (Trexall, and others). Upadacitinib is the third JAK inhibitor to be approved in the US for treatment of RA; tofacitinib (Xeljanz, Xeljanz XR) and baricitinib (Olumiant) were approved earlier.

The FDA has required updates to the labeling of the Janus kinase (JAK) inhibitor tofacitinib (Xeljanz, Xeljanz XR) based on interim results of a postmarketing safety trial that showed an increased risk of pulmonary thromboembolism and death with a dosage of 10 mg twice daily.1 Tofacitinib is approved for treatment of rheumatoid arthritis (RA),2 psoriatic arthritis, and ulcerative colitis.

In the postmarketing trial, RA patients ≥50 years old taking methotrexate who had at least one cardiovascular risk factor were randomized to receive add-on treatment with tofacitinib 5 mg twice daily (the FDA-approved dosage for RA and psoriatic arthritis), tofacitinib 10 mg twice daily (an approved dosage for ulcerative colitis), or a tumor necrosis factor (TNF) inhibitor. At the time of the interim analysis in January 2019 (~3900 patient-years of data in each group), pulmonary thromboembolism had occurred in 19 patients taking tofacitinib 10 mg twice daily and in 3 patients taking a TNF inhibitor; 45 patients taking tofacitinib 10 mg twice daily and 25 taking a TNF inhibitor had died. Interim data from the 5-mg twice daily group have not been made available by the FDA. After the interim analysis, patients taking the higher dose of tofacitinib were transitioned into the 5 mg twice daily group; the trial is ongoing.3

Serious, sometimes fatal thromboembolic adverse events have also occurred with use of baricitinib (Olumiant),4 another JAK inhibitor that is FDA-approved for treatment of RA. Whether an increased risk of thromboembolism is a class effect of JAK inhibitors remains to be determined; RA itself has been associated with an increased thromboembolic risk.5

The tofacitinib package insert now contains a boxed warning describing the increased risk of thrombosis and mortality with a dosage of 10 mg twice daily and emphasizes that this dosage or Xeljanz XR 22 mg once daily is not recommended for treatment of RA or psoriatic arthritis. For treatment of ulcerative colitis, tofacitinib is now only indicated in patients who have had an inadequate response or intolerance to TNF inhibitors; for these patients, the 10-mg twice daily dosage is still recommended as induction therapy for 8 weeks (can be continued for up to 16 weeks) and for maintenance treatment when there is loss of response to a dosage of 5 mg twice daily.

1. FDA drug safety communication: FDA approves boxed warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR). July 26, 2019. Available at: www.fda.gov. Accessed August 15, 2019.
2. Tofacitinib for rheumatoid arthritis. Med Lett Drugs Ther 2013; 55:1.
3. FDA drug safety communication: Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients; FDA to investigate. February 25, 2019. Available at: https://www.fda.gov. Accessed August 15, 2019.
4. Baricitinib (Olumiant) for rheumatoid arthritis. Med Lett Drugs Ther 2018; 60:120.
5. IC Scott et al. Thromboembolism with Janus kinase (JAK) inhibitors for rheumatoid arthritis: how real is the risk? Drug Saf 2018; 41:645.

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Disease-modifying antirheumatic drugs (DMARDs) are used for initial treatment of rheumatoid arthritis (RA) to achieve clinical remission and prevent irreversible joint damage (see Table 1). DMARDs generally do not have an immediate analgesic effect, but over time they can control symptoms and have been shown to delay and possibly stop progression of the disease. Methotrexate (Trexall, and others) is generally the drug of choice; it can be used for patients with low, moderate, or high disease activity. For mild disease, some clinicians prefer to start with hydroxychloroquine (Plaquenil, and generics) and/or sulfasalazine (Azulfidine, and others).

View Expanded Table: Biologic Agents for Rheumatoid Arthritis

The FDA has approved the Janus kinase (JAK) inhibitor baricitinib (Olumiant – Lilly) for oral treatment of adults with moderately to severely active rheumatoid arthritis (RA) that has not responded adequately to one or more tumor necrosis factor (TNF) inhibitors. Baricitinib is the second JAK inhibitor to be approved for treatment of RA; tofacitinib (Xeljanz, Xeljanz XR) was the first.

Management of both ulcerative colitis (UC) and Crohn's disease (CD) is based on disease severity. Disease location (proctitis, left-sided colitis, or extensive colitis) also plays a role in drug selection. Some drugs for induction and maintenance of remission of inflammatory bowel disease (IBD) are listed in Table 1.

View Table: Drugs for Ulcerative Colitis

View Table: Safety of Drugs for IBD in Pregnancy

View Expanded Table: Some Drugs for Inflammatory Bowel Disease

The FDA has approved the interleukin (IL)-6 inhibitor sarilumab (Kevzara – Sanofi) for second-line treatment of adults with moderately to severely active rheumatoid arthritis (RA). It is the second IL-6 inhibitor to be approved for this indication; tocilizumab (Actemra) was approved earlier.

Mild to moderate psoriasis is generally treated with topical corticosteroids. Vitamin D analogs and tazarotene are topical alternatives that can be used in combination with topical corticosteroids. Phototherapy and systemic therapy, including biologic agents, are recommended for patients with moderate to severe disease.

For initial treatment of rheumatoid arthritis, most expert clinicians prescribe a disease-modifying antirheumatic drug (DMARD) and add a nonsteroidal anti-inflammatory drug (NSAID) or a corticosteroid to control symptoms. Methotrexate is generally the DMARD of choice...

DMARDs
Disease-modifying antirheumatic drugs (DMARDs) are used early in the treatment of rheumatoid arthritis (RA) to achieve clinical remission, prevent irreversible damage to joints, and minimize toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. DMARDs generally do not have an immediate analgesic effect, but over time can control symptoms and have been shown to delay and possibly stop progression of the disease. Methotrexate (Rheumatrex, and others) is generally the first DMARD prescribed; it can be used to treat mild, moderate, or severe RA. For mild disease, some clinicians prefer to start with hydroxychloroquine (Plaquenil, and generics) and/or sulfasalazine (Azulfidine, and others).

The FDA has approved tofacitinib (toe” fa sye’ ti nib; Xeljanz – Pfizer), an oral Janus kinase (JAK) inhibitor, for treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to or are intolerant of methotrexate. Ruxolitinib (Jakafi) is the only other JAK inhibitor available in the US; it is FDA-approved for treatment of myelofibrosis.

The pathogenesis of acne is multifactorial: follicular hyperkeratinization, bacteria, sebum production, androgens, and inflammation all play a role. The gram-positive microaerophilic bacteria Propionibacterium acnes promote development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.