| nd-color: #ffffff;" /> | | | | demonstrated greater effectiveness when used in |
| Rheumatoid arthritis is a chronic, progressive, | | | | combination with MTX. |
| systemic disease that affects more than 2.1 million | | | | In all three studies, the number of patients achieving |
| Americans. | | | | remission as defined by a scoring system known as |
| Because it is a systemic disease it affects more than | | | | the Disease Activity Score (DAS) 28 was twice that |
| just the joints. | | | | seen in the single drug group and approached 40%. |
| Other organ systems that may be adversely | | | | These studies clearly showed that TNF inhibitors in |
| affected include the eyes, lungs, central and | | | | combination with MTX was the most effective |
| peripheral nervous system, skin, heart, and blood. | | | | regimen available for RA patients. |
| Long term complications of rheumatoid arthritis | | | | But, what about side effects? |
| include early death from heart attack and stroke, the | | | | While there were early concerns about the |
| development of lymphoma, and disability. | | | | development of increased risk for B-cell non-Hodgkin's |
| Early aggressive therapy with slow-acting disease | | | | lymphoma in patients treated with these drugs, there |
| modifying drugs (DMARDS) such as sulfasalazine | | | | has not been a definite link between TNF inhibitors |
| (Azulfidine), methotrexate, hydroxychloroquine | | | | and lymphoma. |
| (Plaquenil), leflunomide (Arava), and azathioprine | | | | Studies before the advent of biologic drugs |
| (Imuran) have shown that many of these potential | | | | demonstrated that RA disease severity was |
| systemic problems can be mitigated. Yet, until | | | | associated with increased lymphoma risk; however, |
| recently, remission was an elusive target. | | | | several studies involving RA patients who have since |
| With the advent of newer biologic therapies, the | | | | been treated with TNF inhibitors demonstrated no |
| possibility- and probability of remission has increased | | | | increase in lymphoma incidence compared with RA |
| several-fold. | | | | patients on MTX. |
| The first biologic drugs are the tumor necrosis factor | | | | No studies have demonstrated an increase in solid |
| (TNF) inhibitors. These drugs block the effect of a | | | | tumor malignancy in patients treated with TNF |
| protein messenger that is responsible for much of | | | | inhibitors, except for reports of non-melanoma skin |
| the inflammation and destruction that occurs in RA. | | | | cancers. |
| The three TNF inhibitors (etanercept [Enbrel], | | | | Nonetheless, what is not known is the risk for cancer |
| infliximab [Remicade], and adalimumab [Humira]) were | | | | in patients with previous malignancy who are |
| demonstrated to have significant clinical benefits in | | | | receiving TNF inhibitors. |
| randomized trials that resulted in their US Food and | | | | Experience culled from clinical trials as well as real life |
| Drug Administration (FDA) approval. | | | | data has shown that adverse events, such as upper |
| Patients enrolled in these trials had severe RA | | | | respiratory infections, are increased with TNF inhibitor |
| disease, as reflected by more than 20 swollen and 30 | | | | treatment. Some studies have indicated that there is |
| tender joints and baseline scores measuring their | | | | an increased risk for serious infection with these |
| ability to perform activities of daily living consistent | | | | drugs as well. |
| with extremely poor functioning. | | | | Currently, the feeling is that patients receiving biologic |
| Improvement in signs and symptoms as measured | | | | therapies are at risk for serious infection, and this is |
| by American College of Rheumatology (ACR) | | | | an issue to be discussed with patients prior to the |
| response were similar for all 3 therapies. Responses | | | | initiation of these therapies. |
| are graded as being a 20 per cent response (ACR | | | | Reactivation of latent TB has been clearly associated |
| 20), a 50 per cent response (ACR 50), and a 70 per | | | | with TNF inhibitor utilization. The use of effective |
| cent response (ACR 70). | | | | screening for TB prior to initiating TNF inhibitors has |
| The higher the response, the better the drug works | | | | reduced the frequency of TB reactivation. |
| on RA. All three TNF inhibitors performed about the | | | | Other types of infection such as Listeria, |
| same, ie., (ACR20 ~60%, ACR50 ~40%, and ACR70 | | | | histoplasmosis, and coccidiomycosis, have been |
| ~20%). | | | | reported in patients receiving TNF inhibitors. |
| Patients having either early or long-standing RA | | | | Injection site reactions or infusion reactions have |
| demonstrated significant response. In addition to | | | | been reported and treatment needs to be cut back |
| improvement in signs and symptoms, dramatic | | | | or stopped if these reactions persist. |
| reduction in x-ray progression was noted as well as | | | | TNF-inhibitor treatment is contraindicated in patients |
| improvement in health-related quality of life and | | | | with class III-IV congestive heart failure. These drugs |
| physical function and disability. This is not surprising | | | | can make the heart failure worse. |
| since x-ray progression is intimately correlated with | | | | Patients with neurologic conditions in which there is |
| both reduction in functionality as well as the eventual | | | | demyelination such as multiple sclerosis are not |
| development of disability. | | | | considered to be good candidates for TNF inhibitor |
| Subsequent studies comparing TNF inhibitors in | | | | therapy. Rare reports of patients developing a |
| combination with MTX vs MTX alone, or in the case | | | | demyelinating condition have been noted. |
| of etanercept and adalimumab an additional | | | | Liver failure has been seen in patients on TNF |
| comparison with TNF inhibitor single drug use, | | | | inhibitors. |