Decernotinib, Subcutaneous Methotrexate Drug Updates, Trials, Approvals

Decernotinib (VX-509), a selective oral Janus kinase 3 inhibitor, is currently in Phase 2b for the treatment of rheumatoid arthritis (RA).¹

Decernotinib efficacy and safety were evaluated in a 24-week, randomized, double-blind, placebo-controlled study in 358 adults with active RA (C-reactive protein [CRP] greater than the upper limit of normal, ≥6 [of 66] swollen joints and ≥6 [of 68] tender joints) taking stable doses of methotrexate (MTX). Most patients were women with a mean age of 53 years and an average disease duration of seven years. These patients were randomized to receive placebo or decernotinib at a dose of 100 mg once daily, 150 mg once daily, 200 mg once daily or 100 mg twice daily.

At Week 24, the following percentage of decernotinib-treated patients achieved an ACR20 of 61% (100 mg daily; 150 mg daily; 200 mg daily) and 63% (100 mg BID), compared with 17% of placebo-treated patients (P<0.001 for all). Both ACR50 and ACR70 results at Week 24 were also clinically and statistically significant, as were DAS28 (CRP) <2.6, DAS28 (ESR) <2.6 and the decrease from baseline in DAS28 (CRP). Adverse events (AEs) were slightly higher in the active treatment groups compared to placebo (60% vs. 43%), with 9% of decernotinib-treated patients discontinuing treatment and 42% of placebo-treated patients discontinuing treatment. The most common AEs were headache (9%), hypercholesterolemia (5%) and diarrhea (5%). Serious infections were more common in the decernotinib-treated patients compared with placebo-treated patients (3.5% vs. 1.4%). Minor laboratory abnormalities included transaminase elevations, and decreased median lymphocyte and neutrophil counts. There were two deaths; one was due to cardiac failure in the 100 mg twice daily treatment group, and one was due to pancytopenia in a patient with pneumonia who was in the 200 mg daily treatment group.

Methotrexate subcutaneous (SubQ) auto-injector pen (Rasuvo) has been approved by the Food and Drug Administration (FDA) for managing RA, polyarticular-course juvenile idiopathic arthritis and disabling, recalcitrant psoriasis.² It will be available in packages of one and four pens, in 10 dosage strengths, ranging in 2.5 mg increments from 7.5 mg to 30 mg.2 These strengths include: 7.5 mg/0.15 mL, 10 mg/0.20 mL, 12.5 mg/0.25 mL, 15 mg/0.30 mL, 17.5 mg/0.35 mL, 20 mg/0.40 mL, 22.5 mg/0.45 mL, 25 mg/0.50 mL, 27.5 mg/0.55 mL and 30 mg/0.60 mL.³

Oxycodone hydrochloride/naloxone hydrochloride extended-release tablets (Targiniq ER) have been FDA approved as a long-acting, extended-release, abuse-deterrent formulation for daily, around-the-clock, long-term opioid treatment.⁴ Properties of this formulation are expected to deter drug abuse by injection or snorting. When the formulation is crushed and snorted, or dissolved and injected, naloxone in this formulation blocks the euphoric effects of oxycodone, thus making it less likely to be abused compared with other opioid products, which contain only oxycodone.

Drug Safety

The FDA has withdrawn more than 100 Abbreviated New Drug Applications for prescription combinations that contain more than 325 mg of acetaminophen per dosage unit in order to protect patients from inadvertent acetaminophen overdose.⁵ The National Association of Board of Pharmacy has recommended that pharmacies no longer dispense combination products that contain more than 325 mg acetaminophen per dosage unit. Pharmacists and prescribers should discuss alternative analgesic products that contain lower acetaminophen doses for patients who require pain management.

Following a median exposure of 2.4 years, serious adverse drug events (SAEs) in tofacitinib-treated patients with RA have remained stable and have not increased.⁶ In a safety analysis presented at the Annual European Congress of Rheumatology (EULAR 2014) in June, 5,671 patients representing 12,644 patient-years of tofacitinib exposure showed stable AE rates with no new risks identified compared to prior reports. Patients were included from Phases 2 and 3 and open-label extension clinical trials. Patients received tofacitinib for at least 48 months (n=555), 36 months (n=1,948), 24 months (n=3,804) and 12 months (n=4,204), with 16.3% (n=926) discontinuing treatment due to AEs. Infections, including disseminated and multidermatomal herpes zoster, were the most serious AEs (SAEs). Nonmelanoma skin cancer (NMSC) rates were low at 0.85% per 100 patient-years, and lymphoma and lymphoproliferative disorder rates were similar across the time intervals. Cancer rates (excluding NMSC) were comparable to U.S. Surveillance, Epidemiology and End Results Program (SEER) rates from cohorts of RA patients who were treated with tumor necrosis factor inhibitors. Non-serious and serious herpes zoster infections occurred at a rate of 4.22 (95% CI, 3.87, 4.61).

In July, the Drug Enforcement Agency rescheduled tramadol and its salts and isomers into the controlled substance category IV (C-IV) under the Controlled Substances Act.⁷ Beginning Aug. 18, 2014, the C-IV designation was mandated of drug manufacturers to be placed on any tramadol-containing products. The scheduling of tramadol was based on a review of existing data, including concern regarding its addictive, abusive and diversion potential. Thirteen states, including New York, Mississippi and Arkansas, had already placed tramadol into C-IV.⁸

Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

Drug Safety

References

Biosimilar for Infliximab Launched in Europe

Drug Updates

FDA Approves Oral Methotrexate; Plus Restrictions for 2 Analgesics in Children

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Drug Safety

References

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