Table 3.

Summary of off-label biological agents used in the treatment of nonspecific orbital inflammation.

Drug	Structure	Studies	Side Effects a	References
Anti-TNF agents
Infliximab	Mouse-human chimera monoclonal antibody	Great efficacy in treating NSOI. Induced a decrease in systemic corticosteroid need at a dose of 7.00 ± 6.83 mg/day. Long-term remission achieved in 85% of patients with NSOI.	Dynamic pharmacokinetics with variable terminal half-life times. Mostly associated with optic neuritis. Negatively influenced by NFκB upregulation.	[158,159,160,161,162,163,164,165,166,167]
Adalimumab	Human monoclonal antibody	Lower efficacy: 1-year remission observed in 43% of patients with NSOI.	Associated with higher levels of arthralgia and nausea. Negatively influenced by NFκB upregulation.	[158,163,165,166,168]
Etanercept	Soluble TNFR2-Fc recombinant protein	Lack of evidence regarding clinical remission in patients with IBD.	Mostly associated with optic neuritis. Negatively influenced by NFκB upregulation.	[158,165,166,167,169]
B-cell modulating agent (anti-CD20)
Rituximab	Humanized chimeric anti-CD20 monoclonal antibody	Successful efficacy in refractory NSOI. Post-therapeutic response in 88% of patients, with the absence of side effects in 83% of participants. Disease remission at 1 year achievable with IV infusion of 100 mg on days 1 and 15.	Very few side effects. Disease recurrence in 11% of patients.	[170,171,172,173,174,175]
Anti-IL-6 receptor agents
Tocilizumab	Humanized monoclonal IgG1 antibody	Prevents NSOI recurrence over 6 years, at least at a maintenance dose of 4 mg/kg. Uncontrolled inflammation at 9 months with 8 mg every 4 weeks.	Associated with higher levels of depression.	[176,177,178,179,180,181]

^a Side effects encompass those outlined in various autoimmune and inflammatory diseases. Abbreviations: NSOI, nonspecific orbital inflammation; IBD, inflammatory bowel disease.