Brodalumab Approved for Plaque Psoriasis, Plus Baricitinib Effiicacy Studied for RA

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Brodalumab Approved for Plaque Psoriasis

The U.S. Food and Drug Administration has approved brodalumab, a monoclonal antibody that targets interleukin 17 (IL‑17).^1,2 Brodalumab (Siliq) was approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy and have failed to respond to, or have lost response to, other systemic therapies. The treatment, which is administered as a subcutaneous injection, binds to the IL-17 receptor and inhibits inflammatory signaling by preventing the binding of several IL-17 types to the receptor.

Brodalumab has a Boxed Warning for risks in patients with a history of suicidal thoughts or behavior. Therefore, the treatment was approved with a Risk Evaluation and Mitigation Strategy (REMS). The REMS involves a one-time enrollment for physicians and a one-time informed consent for patients. Suicidal ideation and suicidal behavior have been reported with this agent.

In three randomized, placebo-controlled clinical trials, the safety and efficacy of brodalumab was established in 4,373 adults with moderate to severe plaque psoriasis who were candidates for systemic therapy or phototherapy. More brodalumab-treated patients compared with placebo-treated patients achieved 100% improvement in the psoriasis area and severity index (PASI100). This primary endpoint meant that patients had skin that was clear, or almost clear, at the end of the study.

The most common adverse reactions in clinical trials were arthralgia, diarrhea, fatigue, headache and oropharyngeal pain. Brodalumab is contraindicated in patients with Crohn’s disease. Serious infections have occurred in patients treated with the agent. Therefore, physicians should exercise caution when considering brodalumab use in patients with a chronic infection or a history of recurrent infection. Patients should be evaluated for tuberculosis infection prior to starting therapy.

Brodalumab will be marketed beginning in the second half of this year.

Baricitinib May Exhibit Better Efficacy Than Adalimumab for RA

Baricitinib, an investigational, oral, reversible inhibitor of Janus kinases JAK1 and JAK2, has completed the RA-BEAM, Phase 3 clinical trial.³ This study was a 52-week, randomized, double-blind, placebo- and active-controlled, parallel-group trial conducted in 26 countries.

Participants (n=1,307) were randomized into groups (3:3:2) to receive placebo, 4 mg baricitinib once daily or 40 mg of subcutaneous adalimumab every other week. Patients also continued background therapy with conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), analgesics or glucocorticoids (≤10 mg prednisone or the equivalent per day). Placebo patients were switched to baricitinib at Week 24, maintaining study blinding. Most patients received background methotrexate (>99%) and the majority of patients had previously received at least two conventional synthetic DMARDs. The ACR20 response at Week 12 was the primary endpoint. Secondary endpoints included measurement of the DAS28, the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Simplified Disease Activity Index (SDAI). The modified total Sharp score (mTSS) at Week 24 was also a secondary endpoint.

At Week 12, more baricitinib-treated patients had an ACR20 response compared with placebo-treated patients (70% vs. 40%, P<0.001). All of the secondary endpoints improved for the baricitinib-treated patients compared with placebo-treated patients, including the mTSS at Week 24. In the active-controlled treatment group receiving adalimumab, 61% of patients achieved ACR20 at Week 12 compared with 70% of baricitinib-treated patients. Baricitinib was deemed to be noninferior to adalimumab at Week 12 for the ACR20 response. At Week 52, a higher proportion of baricitinib-treated patients achieved ACR50 and ACR70 compared with adalimumab-treated patients.

Rates of study discontinuation due to adverse events were relatively low from baseline to Week 24. Discontinuation rates were 3% for placebo-treated patients, 5% for baricitinib and 2% for adalimumab. Serious adverse event rates through Week 24 were 5%, 5% and 2% for placebo, baricitinib and adalimumab, respectively. Through Week 52, serious adverse events occurred in 8% of baricitinib-treated patients and 4% of adalimumab-treated patients. Baricitinib-treated patients (71%) and adalimumab-treated patients (68%) had more frequent adverse events than placebo-treated patients (60%). Infection rates in baricitinib-treated patients (48%) and adalimumab-treated patients (44%) were similar through Week 52.

An adalimumab-treated patient developed tuberculosis. Cancers occurred in five patients (n=2 baricitinib-treated patients; n=3 placebo-treated patients). Baricitinib was also associated with neutrophil count lowering, creatinine increases and low-density lipoprotein cholesterol increases. Five deaths were also reported (n=2 for baricitinib, n=1 for placebo to baricitinib, n=1 for adalimumab and n=1 for placebo).

This study showed that RA patients with an inadequate response to conventional DMARDs, including methotrexate, may obtain significant clinical improvement with baricitinib.

Baricitinib has already been submitted for regulatory review in the U.S.⁴ Baricitinib (Olumiant) was granted marketing authorization in Europe by the European Commission in 2 mg and 4 mg film-coated tablets to treat moderate to severe active RA in adults who have had an inadequate response to, or who are intolerant to, one or more DMARDs.⁵

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

References

1. U.S. Food and Drug Administration. News release: FDA approves new psoriasis drug. 2017 Feb 15.
2. Valeant Pharmaceuticals International Inc. News release: Valeant receives FDA approval of Siliq (brodalumab) for moderate to severe plaque psoriasis. 2017 Feb 16.
3. Taylor PC, Keystone EC, van der Heidje D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376:652–662. doi: 10.1056/NEJMoa1608345.
4. Eli Lilly and Co. News release: Additional results from pivotal RA-BEAM study published in New England Journal of Medicine show baricitinib-treated patients demonstrated sustained improvement in rheumatoid arthritis compared to adalimumab and placebo. 2017 Feb 15. .
5. Eli Lilly and Co. News release: European commission approves once-daily Olumiant tablets for treatment of adults with moderate to severe active rheumatoid arthritis. 2017 Feb 13.