Treatment with Simponi (golimumab) reduced the incidence of a type of eye inflammation called acute anterior uveitis (AAU) and decreased disease activity in patients with ankylosing spondylitis (AS), according to a Phase 4 clinical study in a real-world setting.
AAU, which affects the middle layer of the eye, is the most common extraarticular (outside a joint) manifestation in patients with AS. It causes severe pain, redness, photophobia (light sensitivity), and blurred vision.
Studies have identified genes implicated in both AS and AAU, with the pro-inflammatory molecule TNF-alpha suggested as an important mediator of both disorders. As such, use of TNF inhibitors (TNFi) appears to reduce the occurrence of AAU in AS, contrary to treatment with nonsteroidal anti-inflammatory drugs (NSAID), the first treatment step in AS.
It is not yet know whether patients who develop their first AAU during treatment with TNFi are reacting to a TNFi or whether the attacks are part of the normal pattern and do not sufficiently respond to these inhibitors.
Data on the occurrence of AAU during AS treatment with Simponi — a TNFi — are limited and come from studies with a small number of patients. Data on Simponi’s efficacy in routine daily practice are also still lacking.
Aiming to address these gaps, researchers conducted the prospective, multicenter GO-EASY Phase 4 study (NCT01668004), which compared the annual incidence rate of AAU in patients with AS prior to their first TNFi therapy and following 12-month treatment with Simponi.
The study’s secondary goal was to determine the effectiveness and safety of Simponi in AS disease activity as assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) in routine daily practice. ASDAS is a validated measure of disease activity based on the scores of five domains: back pain, joint pain and/or swelling, morning stiffness, global assessment of disease activity, and levels of C-reactive protein (a blood marker of inflammation). The higher the score, which varies between less than 1.3 and more than 3.5, the higher the disease activity.
The trial — sponsored by MSD, known as Merck in the U.S. and Canada — included 93 patients — mean age 44 years, 65% male, 55% not treated with a TNFi, and 27% with a history of AAU. For the 45% of patients who had taken a TNFi — thereby switching to Simponi — the median time since the year before the first TNFi therapy was 5.2 years.
Median disease duration was seven years and ASDAS score 3.1. Study visits were conducted one, three, six, nine, and 12 months after treatment initiation. Simponi was given subcutaneously at a dose of 50 mg once a month.
Clinically relevant improvement was defined as a 1.1-unit or more change in the ASDAS score, with major improvement defined as a change of 2.0 units or more. In turn, response to treatment was defined as an improvement in the Assessment of Spondyloarthritis International Society (ASAS20) score of more than 20% and a reduction of over 10 units in at least three of four domains.
In the year before starting TNFi therapy, seven patients had a total of 10 AAU attacks. Five patients had AAU at baseline, four of whom had taken Simponi. Two patients reported two new AAU attacks during treatment with Simponi, both with a history of AAU. Of note, previous data showed that patients who switch TNFis have a lesser chance of response to the new medication.
Treatment with Simponi was associated with a reduction in AAU occurrence rate from 11.1 to 2.2 per 100 patient-years, a measure obtained by multiplying the number of persons at risk per time.
After three months of treatment, 41% of patients had clinically relevant improvement and 19% major improvement in the ASDAS score. The data further showed that 36% had significant treatment response (achieved an ASDAS20 response), which increased to 49% at one year of treatment. Most other variables of disease activity also showed significant improvement at 12 months.
As for treatment compliance, 17 patients (83% male) discontinued treatment due to: lack of effect (eight), adverse events (five), no treatment compliance (two), or a decision to stop study participation (two). Also, 80% of the 101 patients initially enrolled experienced at least one adverse event, mostly related to the typical TNFi side effects, such as mild infections and injection site reactions.
Twelve serious adverse events were reported in seven patients, five of whom required hospital admission. These events included infections, exacerbation of ulcerative colitis, large intestinal ulcer hemorrhage, hypovolemic shock (loss of blood resulting in insufficient blood being pumped by the heart) after hemorrhage, prostate cancer, cellulitis — a bacterial infection in the skin — bursitis, acute coronary syndrome, and cardiac failure.
“In AS, the AAU occurrence rate and disease activity decreased significantly during [Simponi] treatment,” researchers said. “Therefore, [Simponi] can be considered a good choice in patients with AS who need a TNFi, especially in cases of recurrent AAU.”