Manipulative physiotherapy, therapeutic exercises and chiropractic manipulative therapy shows beneficial results for decreasing pain and increasing spinal range of motion. As areas of the spine and tendons can become inflamed NSAIDs such as ibuprofen and Naproxen can be helpful in both relieving pain and inflammation associated with DISH. It is hoped that by minimizing inflammation in these areas, further calcification of tendons and ligaments of the spine leading to bony outgrowths (enthesophytes) will be prevented, although causative factors are still unknown.

The major types of medications used to treat ankylosing spondylitis are pain-relievers and drugs aimed at stopping or slowing the progression of the disease. All of these have potentially serious side effects. Pain-relieving drugs come in two major classes:

- The mainstay of therapy in all seronegative spondyloarthropathies are anti-inflammatory drugs, which include NSAIDs such as ibuprofen, phenylbutazone, diclofenac, indomethacin, naproxen and COX-2 inhibitors, which reduce inflammation and pain. Indomethacin is a drug of choice. 2012 research showed that those with AS and elevated levels of acute phase reactants seem to benefit most from continuous treatment with NSAIDs.

- Opioid painkillers

Medications used to treat the progression of the disease include the following:

- Disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine can be used in people with peripheral arthritis. For axial involvement, evidence does not support sulfasalazine. Other DMARDS, such as methotrexate, did not have enough evidence to prove their effect. Generally, systemic corticosteroids were not used due to lack of evidence. Local injection with corticosteroid can be used for certain people with peripheral arthritis.

- Tumor necrosis factor-alpha (TNFα) blockers (antagonists), such as the biologics etanercept, infliximab, golimumab and adalimumab, have shown good short-term effectiveness in the form of profound and sustained reduction in all clinical and laboratory measures of disease activity. Trials are ongoing to determine their long-term effectiveness and safety. The major drawback is the cost. An alternative may be the newer, orally-administered non-biologic apremilast, which inhibits TNF-α secretion, but a recent study did not find the drug useful for ankylosing spondylitis.

- Anti-interleukin-6 inhibitors such as tocilizumab, currently approved for the treatment of rheumatoid arthritis, and rituximab, a monoclonal antibody against CD20, are also undergoing trials.

- Interleukin-17A inhibitor secukinumab is an option for the treatment of active ankylosing spondylitis that has responded inadequately to (TNFα) blockers.

There is no cure for AS, although treatments and medications can reduce symptoms and pain.

Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is also called enthesopathy, or any pathologic condition involving the entheses. The entheses are any point of attachment of skeletal muscles to the bone, where recurring stress or inflammatory autoimmune disease can cause inflammation or occasionally fibrosis and calcification. One of the primary entheses involved in inflammatory autoimmune disease is at the heel, particularly the Achilles tendon.

It is associated with HLA B27 arthropathies like ankylosing spondylitis, psoriatic arthritis, and reactive arthritis. Symptoms include multiple points of tenderness at the heel, tibial tuberosity, iliac crest, and other tendon insertion sites.

In medicine, an enthesopathy refers to a disorder involving the attachment of a tendon or ligament to a bone. This site of attachment is known as the entheses.

If the condition is known to be inflammatory, it can more precisely be called an enthesitis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory spondyloarthropathy which predominantly affects the spine. It is characterized by ankylosis and enthesopathy (ossification of the ligaments and entheses). It most commonly affects the thoracic and thoraco-lumbar spine, but involvement is variable and can include the entire spine.

Enthesopathies may take the form of spondyloarthropathies (joint diseases of the spine) such as ankylosing spondylitis, plantar fasciitis, and Achilles tendinitis. Enthesopathy can occur at the elbow, wrist, carpus, hip, knee, ankle, tarsus, or heel bone, among other regions. Further examples include:

- Adhesive capsulitis of shoulder

- Rotator cuff syndrome of shoulder and allied disorders

- Periarthritis of shoulder

- Scapulohumeral fibrositis

- Synovitis of hand or wrist

- Periarthritis of wrist

- Gluteal tendinitis

- Iliac crest spur

- Psoas tendinitis

- Trochanteric tendinitis

Spinal enthesopathy is a form of enthesopathy affecting the spine.

Spondyloarthropathy or spondyloarthrosis refers to any joint disease of the vertebral column. As such, it is a class or category of diseases rather than a single, specific entity. It differs from spondylopathy, which is a disease of the vertebra itself. However, many conditions involve both spondylopathy and spondyloarthropathy.

Spondyloarthropathy with inflammation is called axial spondyloarthritis. In the broadest sense, the term spondyloarthropathy includes joint involvement of vertebral column from any type of joint disease, including rheumatoid arthritis and osteoarthritis, but the term is often used for a specific group of disorders with certain common features, the group often being termed specifically seronegative spondylarthropathies. They have an increased incidence of HLA-B27, as well as negative rheumatoid factor and ANA. Enthesopathy is also sometimes present in association with seronegative.

Non-vertebral signs and symptoms of degenerative or other not-directly-infected inflammation, in the manner of spondyloarthropathies, include asymmetric peripheral arthritis (which is distinct from rheumatoid arthritis), arthritis of the toe interphalangeal joints, sausage digits, Achilles tendinitis, plantar fasciitis, costochondritis, iritis, and mucocutaneous lesions. However, lower back pain is the most common clinical presentation of the causes of spondyloarthropoathies; this back pain is unique because it decreases with activity.

"Seronegative spondyloarthropathy" (or "seronegative spondyloarthritis") is a group of diseases involving the axial skeleton and having a negative serostatus.

"Seronegative" refers to the fact that these diseases are negative for rheumatoid factor, indicating a different pathophysiological mechanism of disease than what is commonly seen in rheumatoid arthritis.