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Furthermore, RA is also thought to be driven by a generation of neoantigens through post-translational modifications of proteins, most commonly by citrullination (also known as deimination)the replacement of the ketamine group in arginine with a ketone group, which effectively removes the positive charge of arginine at neutral pH and converts arginine to the non-coded amino acid citrulline [208, 209]

The challenge facing this strategy is that monotherapies often have varying pharmacokinetics and pharmacodynamics including half-life [69], meaning that the balance of target-receptor agonism may vary over time when using two different agents with varying profiles