medwireNews: A preliminary proof-of-concept study suggests ritlecitinib (PF-06651600), a selective Janus kinase (JAK)3 inhibitor, may offer a novel treatment option for patients with moderate-to-severe rheumatoid arthritis (RA) who have had an inadequate response to methotrexate.
Jean Beebe (Pfizer Inc, Cambridge, Massachusetts, USA) and team say that the “treatment was associated with statistically significant improvements in RA disease scores […] and was generally well-tolerated across the 8-week trial.”
But they acknowledge: “Additional trials will be required to understand the safety and efficacy of [ritlecitinib] with a longer treatment duration.”
Seventy patients with moderate-to-severe RA, who were seropositive for anticitrullinated protein antibodies, rheumatoid factor, or both, were enrolled for the phase 2a study from 32 centers across nine countries.
The patients were randomly assigned to receive ritlecitinib 200 mg/day (n=42) or placebo (n=28) for 8 weeks (median 57 days) and continued taking their pretreatment doses of methotrexate, at a median of 15 mg and 16 mg in the respective groups.
At 8 weeks, there was a significantly greater reduction in RA disease activity in patients taking ritlecitinib compared with those taking placebo, with SDAI scores decreasing from baseline by a mean of 26.1 versus 16.8 points. A significant difference between the two groups was evident from week 6 of treatment, the researchers note in Arthritis & Rheumatology.
In total, three patients – all taking ritlecitinib – achieved remission (SDAI ≤3.3 points), and 10 ritlecitinib-treated patients versus two placebo-treated patients achieved low disease activity (SDAI ≤11 points).
However, the change from baseline in HAQ-DI scores did not significantly differ between the ritlecitinib and placebo groups, which Beebe and team say “may be due to the short study duration or the small number of patients included.”
The authors describe the majority (77.8%) of treatment-emergent adverse events (TEAEs), of which infections and skin disorders were the most common, as “mild in severity,” with no serious TEAEs or deaths reported.
TEAEs considered to be treatment related were evident in nine patients receiving ritlecitinib versus one patient receiving placebo. Treatment-related AEs leading to discontinuation of ritlecitinib included suicidal ideation and mild hepatotoxicity in each of two patients. An additional patient discontinued ritlecitinib due to mild lymphopenia, but this was not considered to be treatment related.
Beebe and researchers stress that “[r]esults from this trial support further exploration of [ritlecitinib] in patients with RA and other inflammatory conditions,” adding that ritlecitinib has already been designated a Breakthrough Therapy by the US FDA for treatment of alopecia areata.
And they conclude that “[f]urther preclinical, pharmacokinetic, and clinical studies are required to fully characterize the [ritlecitinib] selectivity profile and determine the associated clinical consequences and optimal dose” for patients with RA.
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Arthritis Rheumatol 2020; doi:10.1002/art.41316