Rheumatoid arthritis

Baricitinib (OLUMIANT) approved in Australia for treatment of moderate to severe RA

Wednesday, 21 Mar 2018


The oral JAK1 and JAK2 inhibitor baricitinib (OLUMIANT) has been approved by the Therapeutic Goods Administration for the treatment of moderate to severe active rheumatoid arthritis in adults who have responded inadequately, or who are intolerant, to one or more disease-modifying anti-rheumatic drugs.

RA-BEAM study

The RA-BEAM study published in the New England Journal of Medicine in 20171 identified significant clinical improvement with baricitinib compared to placebo and also to active treatment with adalimumab, which the study team described as a “standard-of-care” biologic DMARD.

The 52-week trial randomised 1,307 patients with active RA who were receiving background methotrexate to the addition of placebo (switched to baricitinib after 24 weeks), baricitinib 4 mg/day or adalimumab 40 mg every 2 weeks. Patients had a mean disease duration of 10 years, and about 75% had three or more erosions.

The primary endpoint was the comparison of ACR20 responses at week 12 on baricitinib and placebo. Baricitinib was significantly superior (70% vs 40%, P<0.001). ACR20 responses were sustained at weeks 24 and 52.

All major secondary objectives were met, including an increased ACR20 response at week 12 with baricitinib versus adalimumab (70% vs 61%, P=0.014). Inhibition of radiographic progression of joint damage according to the modified Total Sharp Score at week 24 was reduced with baricitinib compared to placebo (mean change from baseline, 0.41 vs 0.90, P<0.001).

Adverse events, including infections, were more frequent with baricitinib and adalimumab than with placebo to week 24.

Serious adverse events to week 24 were more frequent with baricitinib and placebo than with adalimumab. Baricitinib and adalimumab were both associated with reductions in neutrophil counts, and increases in levels of aminotransferases, creatinine, and LDL and HDL cholesterol.

“In conclusion, in patients with active RA despite receiving therapy with methotrexate, the addition of once-daily oral baricitinib was associated with improvements in signs and symptoms, physical function, patient-reported outcomes, and progression of structural joint damage as compared with placebo and with improvements in ACR20 response and DAS28-CRP as compared with adalimumab,” the researchers said.

Patient-reported outcomes and beyond

A recent report from RA-BEAM provided additional data on patient-reported outcomes.2 There were significantly greater improvement in most outcomes with baricitinib compared with placebo and adalimumab, including physical function, morning joint stiffness, pain, fatigue and quality of life. The improvements were evident at week 12 and were maintained to the end of the study at week 52.

Long-term data on the safety of baricitinib is being accumulated in the RA-BEYOND study.3 An estimated 2,944 patients with RA who have completed a previous baricitinib trial will be treated for an additional seven years.

The primary outcome is the number of participants with one or more drug-related adverse events or any serious adverse events. A wide range of secondary outcome measures includes the proportion maintaining ACR20, ACR50 and ACR70 responses, the proportion maintaining disease remission, changes in modified Total Sharp Score, measures of symptoms, quality of life and disability, and use of healthcare resources.

Baricitinib in practice

Speaking to the limbic, Associate Professor Peter Nash, from the Department of Medicine at the University of Queensland and Director of the Rheumatology Research Unit on the Sunshine Coast, says Australian rheumatologists have rapidly adopted JAK inhibition in the treatment of RA.

“For example, tofacitinib now accounts for close to one-third of initiations after traditional DMARDs have been inadequate or not tolerated. Similarly, it accounts for up to one-third of switches when TNF inhibitors have been inadequate or not tolerated,” he says.

“These figures demonstrate that Australian rheumatologists appreciate the simplicity and convenience of these oral agents with efficacy comparable to biological DMARDs, their efficacy as monotherapy, and a safety profile that is manageable and similar to IL-6 inhibitors that have been in common use for some years.

“The combination of a TNF inhibitor with methotrexate has been one of the gold-standard therapies after traditional DMARDs have been inadequate,” Professor Nash says. “This is why the comparison with adalimumab in the RA-BEAM study is so significant.

“For the first time, a JAK inhibitor/methotrexate combination showed superior efficacy, particularly on pain measures, with rapid onset of action and adverse effects consistent with the rest of the baricitinib clinical trial program.

“As a result there will continue to be an expansion for the JAK inhibitor class in RA management.”

Professor Nash noted that, in the United States, the FDA has requested more information on the appropriate dose of baricitinib and to further characterise thrombosis risk seen as a possible class effect, a disproportion seen in one baricitinib trial and in a second JAK 1 inhibitor under development.

Prescribing baricitinib4

Baricitinib can be prescribed as monotherapy or in combination with conventional DMARDs including methotrexate, but should not be combined with biological DMARDs or other JAK inhibitors.

Treatment should be initiated and monitored by a rheumatologist or specialist physician with expertise in the management of RA.

The standard dose of baricitinib is 4 mg once daily, but 2 mg/day may be acceptable for patients with moderate disease severity, limited risk of progressive joint damage and moderate impairment of physical function. The 2 mg dose can also be considered in patients who have achieved sustained disease control with 4 mg/day and are eligible for dose tapering, and in patients with moderate renal impairment (eGFR 30-60 mL/min/1.73 m2).

 

References

  1. Taylor PC et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med 2017; 376: 652-662.
  2. Keystone EC et al. Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study. Ann Rheum Dis 2017; 76: 1853-1861.
  3. https://clinicaltrials.gov/ct2/show/NCT01885078. Accessed 7 March 2018.
  4. OLUMIANT Approved Product Information, last revised 5 February 2018.

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