medwireNews: Mavrilimumab efficacy is sustained over the long-term treatment of rheumatoid arthritis (RA) without an increase in the incidence of treatment-emergent adverse events (TEAEs), long-term results from two phase IIb trials and an extension study suggest.
For the 442 patients with moderate-to-severe adult-onset RA assessed, who had a median mavrilimumab treatment duration of 2.5 years and a safety exposure of 899 patient–years, most of the TEAEs were mild or moderate in severity. A total of 10% of patients had a TEAE of grade 3 severity or worse.
Previous studies of mavrilimumab, a monoclonal antibody targeting granulocyte-macrophage colony-stimulating factor (GM–CSF) receptor alpha, “evaluated treatment for ≤ 24 weeks; here we have shown that long-term mavrilimumab treatment generated safety data comparable with the phase IIb qualifying studies [EARTH EXPLORER 1 and 2],” report researcher Gerd Burmester (Charité–University Medicine Berlin, Germany) and colleagues.
The most common TEAEs were nasopharyngitis and bronchitis, at respective rates of 7.68 and 5.68 per 100 patient–years. There were low incidences of neutropenia (0.45 per 100 patient–years) and serious infections (1.56 per 100 patient–years) and no reports of monocytopenia.
The two deaths that occurred due to cardiopulmonary failure were not considered to be related to mavrilimumab treatment.
There was also no evidence of pulmonary deterioration with long-term treatment; mean values for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing lung capacity for carbon monoxide remained within 5% of the average baseline values.
At weeks 74 and 104, a clinically relevant decrease (>20% decrease from baseline and ≤80% predicted) in FEV1 occurred in 3.5% and 6.2% of patients, respectively, while the same degree of deterioration was seen for FVC in a corresponding 2.9% and 3.4%. For most patients, these were single events and not associated with respiratory adverse events.
The researchers note that, although patients with uncontrolled pulmonary disease were excluded from all the studies, patients with less severe disease such as asthma and chronic obstructive pulmonary disease were allowed.
“Hence, although these studies may not completely represent the RA patient population, these data are representative of the majority of patients with RA,” they point out in Arthritis & Rheumatology.
In the EARTH EXPLORER 1 study patients had failed to respond adequately to DMARD treatment and were given mavrilimumab, at doses of 30, 100, or 150 mg, or placebo every other week plus methotrexate. Those in the EARTH EXPLORER 2 study had responded inadequately to tumor necrosis factor (TNF) inhibitors (excluding golimumab) and/or DMARDs and received mavrilimumab 100 mg every other week or golimumab 50 mg every 4 weeks with placebo on missing weeks, plus methotrexate.
After 24 weeks, patients entered the open-label phase of the EARTH EXPLORER studies and were given mavrilimumab 100 mg every other week plus methotrexate for up to 158 weeks. Throughout the three studies, 75 patients discontinued mavrilimumab.
Burmester and team report that mavrilimumab treatment was associated with “clear and sustained benefits in measures of RA disease outcomes.” For example, 65.0% of patients achieved low disease activity – defined as a Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) below 3.2 points – at week 122, while 40.6% achieved a score below 2.6.
“This is, to our knowledge, a unique study, as multiple pulmonary function tests were performed in a systematic, long-term longitudinal fashion,” says the team.
“In light of the results […] phase III studies with mavrilimumab (150 mg [every other week]) in RA are advocated.”
By Lucy Piper
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