Patients with psoriatic arthritis (PsA) who achieved persistent minimal disease activity (MDA) on golimumab treatment in the GO-REVEAL trial had better long-term benefits, including functional improvement, global assessment, and radiographic outcomes, than those who did not, according to a post hoc analysis of the GO-REVEAL trial.
Achieving MDA led to greater improvement irrespective of treatment assignment. However, patients treated with golimumab had significantly higher rates of MDA at all time points measured versus placebo.
Achievement of MDA is a more rigorous goal than the typical objectives of therapeutic studies of PsA. "The implications of achieving MDA over a longer time period have not been explored to date....In PsA, achievement of MDA earlier in the disease course could potentially obviate the development of structural damage," wrote Arthur Kavanaugh, MD, University of California San Diego, and coauthors. About half of the golimumab-treated patients achieved MDA at least once.
In GO-REVEAL, patients were randomized to receive golimumab versus placebo for 24 months and then entered an open-label extension study of golimumab 50 mg or 100 mg for up to 5 years.
A total of 405 patients were randomized to receive placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks for 24 months. Stratification was based on baseline use of methotrexate. Patients with <10% improvement from baseline in their swollen joints and tender joint counts at week 16 were randomized from placebo to golimumab 50 mg or from golimumab 50 mg to golimumab 100 mg. Patients already receiving 100 mg of the biologic agent at week 16 remained at this level of treatment regardless of response at week 16.
At week 24, all patients receiving placebo were escalated to golimumab 50 mg. Thus, all patients received either golimumab at 50 mg or 100 mg between weeks 24 and 52.
After week 52, patients underwent open-label treatment with golimumab 50 mg or 100 mg subcutaneous injections every 4 weeks for up to 5 years. Based on investigator discretion, golimumab doses were increased or decreased during the open-label phase.
Criteria for MDA included the presence of ≥5 of 7 PsA outcome measures, as follows: ≤1 swollen joint count of 66 evaluated; ≤1 tender joint count of 68 evaluated; Psoriasis Area and Severity Index ≤1 (range, 0-72); patient pain visual analog scale (VAS) score ≤15 (range, 0-100); patient global assessment of disease activity VAS score of ≤20 (range, 0-100); Health Assessment Questionnaire Disability Index (HAQ-DI) score ≤0.5, and ≤1 tender enthesis point.
Patients had significantly higher MDA response rates on golimumab compared with placebo over the first 52 weeks. Significantly improved MDA response rates were seen at week 14 in 23.5% of the golimumab-treated patients compared with 1.0% of the placebo group (P <.0001); at week 24, MDA response rates were significantly improved in 28.1% versus 7.7%, respectively (P <.0001); and at week 52 in 42.4% versus 30.2%, respectively (P =.037). Irrespective of treatment randomization, achievement of MDA at 3 or ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components at week 256 compared with patients not achieving MDA.
Patients with persistent MDA who received methotrexate at baseline achieved the greatest radiographic benefit. Significantly less radiographic progression was associated with attaining MDA at 3 or ≥4 consecutive time points, and these results were not related to treatment randomization. Logistic regression analysis showed that a 1-unit higher baseline HAQ-DI score was associated with a significantly lower probability of achieving MDA.
About one-third of patients discontinued study treatment through week 252, most commonly for adverse events and unsatisfactory therapeutic response.
- Kavanaugh A, van der Heijde D, Beutler A, et al. Radio-graphic progression of patients with psoriatic arthritis who achieve minimal disease activity in response to golimumab therapy: results through 5 years of a randomized, placebo–controlled study. Arthritis Care Res (Hoboken). 2016;68:267-274.