Lyme disease in horses is usually treated by intravenous tetracycline or oral doxycycline.
In a Cornell University study published in 2005 (Veterinary Microbiology), ponies were experimentally infected with Lyme organisms by infected adult ticks. Twelve weeks later four ponies were assigned to each of three treatment groups, tetracycline, doxycycline or Ceftiofur for 28 days. A fourth group was left untreated. ELISA antibody titers dropped in all the treatment groups, but began to rise again after three months in three of the four doxycycline-treated ponies and two of four Ceftiofur treated. The ponies were necropsied five months after treatment.
The untreated ponies and those that showed a rise in titer after treatment were confirmed to still be infected while there was no evidence of infection in the tetracycline-treated ponies or ponies receiving treatment with another antibiotic whose titers did not rise again.
This study makes intravenous tetracycline the "gold standard" treatment for Lyme disease, but tetracycline is extremely damaging to tissues if it gets outside the vein. The treatment must be administered by a veterinarian. Oral doxycycline is much easier to give, but in that study a 28-day treatment was not sufficient to kill the organism in 75% of the ponies. It's currently unknown whether longer treatment time with doxycycline might more effective.
The ponies' treatment was delayed until three months after the initial infection, so they were beyond the acute stage, but what about horses that might not be diagnosed for much longer? In the human disease, the longer treatment is delayed, the worse the prognosis becomes for cure.
There is also a subset of patients that develop chronic arthritic or neurological problems that persist even with intensive and prolonged antibiotic therapy, including intravenously, and when the infection seems to have been cleared.
There is strong evidence to suggest that in some of these cases auotoimmune disease has developed. The Lyme antibodies are cross-reacting to the horse's own tissue. In other instances, it may well be that the infection has not been completely treated.
Lyme infection in horses is real. When untreated, the organisms can be found in a wide variety of body tissues for at least nine months. Muscles and joints are most often infected.
If the index of suspicion for Lyme is high, because you are in an endemic area and the horse's symptoms are suggestive (e.g. unexplained muscle and/or joint pain, with fever), treatment may be advisable even in the absence of a positive test if other causes have been ruled out.
Whatever treatment course you and your vet decide upon, recheck the titer three months after treatment has stopped. A rising titer at this time likely means the horse still has an active infection.