Absence of recurrent uveitis and local injection site reaction after switching of TNF inhibitor therapy in a patient with AS
History and presentation
In December 2009, a 39-year-old male chronic smoker with a family history of rheumatoid arthritis presented with inflammatory lower back pain and buttocks pain, with spinal stiffness progressing since 2002. No peripheral arthritis, enthesopathy or psoriatic skin lesions were present. The patient had previously been diagnosed with ankylosing spondylitis (AS) in mainland China and was receiving analgesics, including NSAIDs.
Results of serologic testing were positive for human leukocyte antigen-B27 (HLA-B27) but negative for rheumatoid factor (RF), antinuclear antibodies (ANA), hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus (HCV). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were elevated, while serum urate was normal.
Lumbosacral spine X-ray showed increased sclerosis over the inferior parts of the bilateral sacroiliac joints, which was more prominent on the left side, suggestive of sacroiliitis. Furthermore, syndesmophytes were detected in the thoracolumbar junction. The original Schober test[CL2] measurement was 2 cm, indicative of limited range of motion of the lumbar spine. The patient also exhibited a mild stooped posture and limited chest expansion.
Treatment with NSAID for axial AS was initiated for the patient. Sulfasalazine (maximum daily dose, 3 g) added in February 2010 as he refused to switch to a self-financed tumour necrosis factor-a (TNF) inhibitor drug at the beginning.
In January 2014, the patient was tested positive for latent tuberculosis infection on both Interferon Gamma Release Assay (IGRA) and Mantoux test (induration of 10 mm), and was started on isoniazid prophylaxis. Treatment with once-weekly etanercept (50 mg subcutaneously [SC]) was initiated in February 2014, which resulted in good response with normalization of ESR and CRP levels and reductions in Visual Analog Scale (VAS) pain and Bath Ankylosing Spondylitis Functional Index (BASDAI) scores.
The patient developed his first episode of anterior uveitis in the left eye in October 2017 and was treated with prednisolone eye drops, with laser surgery performed in December 2017. However, in view of recurrent uveitis, treatment was switched to adalimumab (40 mg SC once every 2 weeks) in March 2018 upon successful application for financial subsidy.
Despite good control of spinal pain, the patient developed local injection site reaction and generalized urticaria over the entire body after the fifth dose of adalimumab, requiring hospitalization in May 2018. Adalimumab was stopped.
Treatment with golimumab was subsequently initiated in July 2018. After the first two doses, very mild local injection site reaction was observed, which subsided after 1 day with no further recurrence. Furthermore, no urticaria or flares of uveitis had been noted since switching to golimumab. The patient was last seen in May 2019 and remained in satisfactory control of back pain with normalization of ESR and CRP levels.
AS is a subset of axial spondyloarthritis (SpA), which is a broader category of chronic inflammatory diseases affecting the axial skeleton. Axial SpA also encompasses nonradiographic axial SpA.1
AS is characterized by inflammatory back pain that may improve with exercise, radiographic sacroiliitis, excess vertebral bone formation, and a high prevalence of HLA-B27 positivity.1-3 Common extra-articular manifestations found in AS patients include uveitis (30–40 percent), psoriasis (10 percent) and inflammatory bowel disease (IBD) (5–10 percent).1,4 The disease burden from AS can significantly impair physical and social functioning as well as work productivity.5
The goals of AS treatment are to alleviate symptoms, improve functioning, maintain the ability to work, decrease disease complications, and prevent further skeletal damage.6
NSAIDs are regarded as the cornerstone of pharmacological therapy for AS. In adult patients with active AS despite treatment with NSAIDs, current treatment guidelines of the American College of Rheumatology strongly recommend switching to a TNF inhibitor.6 Furthermore, a TNF inhibitor is conditionally recommended in this scenario over treatment with other biologic agents with a different mechanism of action (eg, interleukin-17 inhibitors). In patients with AS-related comorbidities, such as recurrent uveitis or IBD, TNF inhibitor monoclonal antibodies (eg, golimumab) are favoured over other biologics.6
The GO-EASY study demonstrated the clinical efficacy of golimumab in reducing the occurrence rate of uveitis in patients with AS in a real-world setting. This prospective multicentre study compared the annual incidence rate of acute anterior uveitis (AAU) in 93 AS patients during 12 months of treatment with golimumab vs the year before initiating TNF inhibitor therapy. Results showed a significant reduction in AAU occurrence rate during golimumab treatment, from 11.1 to 2.2 per 100 patient-years (rate ratio, 0.2; 95 percent confidence interval [CI], 0.04 to 0.91]).7 (Table)
The development of anti-drug antibodies to TNF inhibitors has been observed in patients with various autoimmune diseases, including SpA, and the rate varies depending on the specific TNF inhibitor and disease.8 Patients who developed these antibodies were shown to have a higher incidence of infusion reactions and injection site reactions compared with those who did not (odds ratio [OR], 3.25; 95 percent CI, 2.35 to 4.51).8 A lower rate of immunogenicity has been demonstrated with golimumab (3.8 percent) compared with other TNF inhibitors, such as infliximab (25.3 percent), adalimumab (14.1 percent) and certolizumab (6.9 percent).8 This might explain why our patient was free of injection site reactions after switching to golimumab.
Golimumab is generally well tolerated. In phase III pivotal trials, 5.1 percent of golimumab-treated patients experienced injection site reactions, with a majority of these being mild to moderate.9
In conclusion, an optimal biologic agent for the treatment of AS should demonstrate long-term clinical efficacy and safety while providing effective control of extra-articular manifestations. With its proven efficacy and favourable safety profile, golimumab may enable AS patients to effectively control their disease and stay on treatment for longer.