2017 Sees Progress in Approvals for Anti-Rheumatic Drugs

Kamala Nola, PharmD, MS, professor at the Lipscomb University College of Pharmacy, provided an overview of the drugs that have been approved in the past year for the treatment of inflammatory conditions during a session at the 2017 American College of Rheumatology Annual Meeting,

The anti-rheumatic therapies approved in 2017 include:

Brodalumab (Siliq). Approved in February, this IL-17 inhibitor is approved to treat moderate to severe plaque psoriasis in patients who are candidates for systemic therapies or phototherapy, and who have failed to adequately respond to other systemic therapies. The drug, delivered subcutaneously via a pre-filled syringe, is contraindicated in Crohn’s disease, and carries a warning for suicidal ideation.

Brodolumab is subject to a risk evaluation and mitigation strategy (REMS) program that requires prescribers to enroll in the program and counsel the patient on suicidal ideation and behavior. Pharmacists are need to be certified to dispense the drug and they have to maintain records that are subject to audits. Patients must carry a wallet card noting their therapy.

Methotrexate (Xatmep). The first oral methotrexate solution, approved in April, is indicated for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) and pediatric acute lymphoblastic leukemia. “This is the first time [methotrexate has] been in an appropriate dosage form” to make the drug palatable to children, Nola said.

Abaloparatide (Tymlos). This human parathyroid hormone related peptide analogue for subcutaneous injection was approved in April to treat postmenopausal women with osteoporosis who have a high risk for fracture. The once-daily 90 mcg subcutaneous injection, taken with supplemental calcium and vitamin D, has no listed contraindications, though it carries warnings that include orthostatic hypotension after injection as well as risk for osteosarcoma, among others.

Tocilizumab (Acterma). “Giant cell arteritis finally has a drug,” said Nola of this therapy. Tocilizumab was granted a label expansion in May for the treatment of adults with giant cell arteritis. The drug, administered as a weekly subcutaneous injection, may be given in combination with a tapering course of steroids, and may allow patients to discontinue steroid therapy altogether.

Tocilizumab was also approved to treat adults and children 2 years or older with chimeric antigen receptor T-cell induced severe or life-threatening cytokine release syndrome.

Sarilumab (Kevzara). This IL-6 receptor antagonist was approved in May to treat adults with moderate to severe active rheumatoid arthritis (RA) who did not respond well or who had intolerance to 1 or more disease-modifying anti-rheumatic drug (DMARD). “We’re finally getting to the point where we can say failure of 1 DMARD [means] you can potentially move on,” said Nola.

Sarilumab may be used as monotherapy or in combination with methotrexate or conventional DMARDs. The drug carries warnings and precautions for severe infection, neutropenia, thrombocytopenia, elevated liver enzymes, gastrointestinal perforation, hypersensitivity reactions, and live vaccines.

Guselkumab (Tremfya). Approved in July, this IL-23 blocker is indicated for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The drug is administered in 100-mg, single-dose, pre-filled syringes, and carries warnings for infection, tuberculosis, and live vaccines.

Belimumab (Benlysta). “Good news for our lupus patients,” said Nola of this drug approved in July. This therapy is available as a self-injectable drug at a 200-mg weekly dose to treat patients with active, autoantibody-positive, systemic lupus erythematosus.

Women who are able to become pregnant should speak to their physicians about using contraception while taking the drug, and for at least 4 months after discontinuing. Belimumab’s manufacturer has made a pregnancy registry available to patients.

Lesinurad and allopurinol (Duzallo). This fixed-dose oral combination of 200 mg of lesinurad, a URATI 1 inhibitor, and 300 mg of allopurinol, a xanthine oxidase inhibitor, was approved in August to treat hyperuricemia with gout in patients who have not reached target serum acid levels with allopurinol therapy alone. Not recommended for asymptomatic hyperuricemia, this therapy has a goal uric acid level of less than 6 mg per dL.

Not more than 1 tablet should be given per day, and patients should be counseled not to combine the drug with lesinurad and to take the therapy in the morning with food and water. Clinicians should assess renal function prior to initiation. The drug carries warnings and precautions for renal events, skin rash and hypersensitivity, hepatoxicity, cardiovascular events, and bone marrow suppression. Listed interactions include mercaptopurine and azathioprine.

Two anti-rheumatic drugs were notable disappointments, earning Complete Response Letters (CRLs) from the FDA in 2017, Nola told the audience.

Baricitinib. “Here’s where we hit a hiccup in the year,” said Nola of baricitinib. This Janus kinase inhibitor for the treatment of RA received a CRL in August. The drug’s developer, Eli Lilly, indicated in a press release that it plans to file a new application to the FDA in January 2018, and expects a 6-month review period.

Sirukumab. The FDA’s Arthritis Advisory Committee did not recommend the approval of this IL-6 inhibitor for the treatment of moderate to severe RA. While the committee unanimously supported sirukumab’s efficacy, it had uncertainty about its safety. The FDA issued a CRL for sirukumab in September.

Nola also provided an update on which biosimilars have been approved to date to treat rheumatic diseases:

• Adalimumab-atto (Amjevita) and adalimumab-abdm (Cyltezo), both referenced on Humira
• Etanercept-szzs (Erelzi), referenced on Enbrel
• Infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis), both referenced on Remicade.

As of the November meeting, only Inflectra and Renflexis have launched in the United States.