Golimumab-methotrexate combo shows potential in psoriatic dactylitis

The addition of the TNFi* golimumab to the conventional synthetic DMARD** methotrexate (MTX) led to greater clinical improvements in dactylitis activity in patients with psoriatic arthritis (PsA) compared with MTX monotherapy, results of the GO-DACT*** trial have shown.

“Dactylitis is a hallmark of PsA for which therapeutic strategies remain empirical,” said the researchers. Dactylitis has not been studied as a primary endpoint but rather a secondary outcome. [J Rheumatol 2014;41:2277-2285; Ann Rheum Dis 2016;75:490-498]

Given the high disease activity and articular erosion risk associated with PsA dactylitis, the European League Against Rheumatism recommends the use of TNFi or biologics to improve function and quality of life. [Arthritis Care Res 2017;69:1692-1699; Ann Rheum Dis 2016;75:499-510]

Forty-four MTX- and biologic DMARD-naïve PsA patients with active dactylitis (84 percent male, median age 45.7 years) were randomized 1:1 to receive MTX with either subcutaneous (SC) golimumab 50 mg or placebo monthly for 24 weeks. MTX was started orally at 15 mg/week, increasing by 5 mg monthly up to a maximum dose of 25 mg/week as tolerated. Switching from oral to SC MTX was allowed in case of gastrointestinal intolerance. [Ann Rheum Dis 2020;79:490-498]

At week 24, golimumab-MTX recipients exhibited significantly greater improvements in Dactylitis Severity Score (DSS) vs those receiving MTX alone (median change, 5 vs 2 points; p=0.026), which manifested as early as 12 weeks (p=0.004).

The fraction of DSS50 and DSS70 responders (ie, 50 or 70 percent improvement in DSS) at week 24 were also substantially greater with golimumab-MTX vs MTX alone (85 percent vs 41 percent; p=0.005 [DSS50] and 60 percent vs 18 percent; p=0.010 [DSS70]).

Greater improvements in the proportion of Leeds Dactylitis Index (LDI) responders were also observed with golimumab-MTX vs MTX alone (100 vs 73 percent; p=0.023 [LDI 20], 100 percent vs 68 percent; p=0.001 [LDI 50], and 95 percent vs 41 percent; p=0.011 [LDI 70]).

The application of DSS and LDI response indices allowed discrimination between groups, which might be useful instruments for future PsA trials, noted the researchers.

Nearly three-quarters (70 percent) of golimumab-MTX recipients had no tenderness (LDI tenderness=0) in the affected digits at week 24, which was threefold higher than the rate observed with MTX alone (21.7 percent).

Adverse event rates were similar between arms and were mostly mild-to-moderate in severity. No new safety signals were reported.

“The primary efficacy endpoint was met [and] key secondary analyses followed a similar pattern … [Our findings] provide strong evidence that the combination of golimumab plus MTX is more efficacious than MTX monotherapy in improving PsA dactylitis,” said the researchers.

“[Given] the high disease burden of dactylitis in PsA patients, including a lower chance of achieving [minimal disease activity] and the risk of structural damage, as well as the advantages of early TNFi intervention, it seems reasonable to argue that patients with PsA active dactylitis could benefit from first-line TNFi plus MTX therapy. We expect that these results will be reproducible with other TNFi combination therapies,” they said.

Despite the small sample size, the findings add data to a limited field of evidence, thus updating clinically useful treatment algorithms targeting optimal management of PsA patients, they noted. Longer follow-ups are warranted to further explore complete resolution of dactylitis and long-term dactylitis remission rates, they added.