For patients with rheumatic arthritis and other chronic inflammatory diseases, discontinuing biologic disease-modifying anti-rheumatic drugs (bDMARDs) prior to orthopaedic surgery does not appear to increase the risk of surgical site infections or delayed wound healing, concludes a review and meta-analysis in The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

However, patients discontinuing bDMARDs may be more likely to experience a disease flare following orthopaedic surgery, according to the report by Bernard H. van Duren of University of Leeds, UK, and colleagues.

Decisions regarding bDMARD discontinuation must balance the risk of disease flares

bDMARDs have represented a major advancement in the treatment of rheumatic arthritis and other inflammatory diseases. Although effective in slowing disease progression, these biologic agents have traditionally been associated with an increased risk of infection.

In the case of total joint replacement, infections are a potentially devastating complication; thus, some surgeons and other specialists recommend discontinuing  bDMARD therapy during the perioperative period. “[H]owever,” the researchers write, “there has been no definitive evidence showing a clear benefit of discontinuing the use of bDMARDs, and in doing so, patients may be at an increased risk for higher disease activity.”

Toward clarifying the issue, Dr. van Duren and colleagues performed a systematic review of 11 studies that included 4,959 patients who discontinued their bDMARDs and 2,385 patients who continued their bDMARDs. The most common diagnosis among these patients was rheumatoid arthritis, and tumor necrosis factor inhibitors were the most common type of bDMARD. However, other diagnoses and bDMARDs were represented.

The meta-analysis found no significant difference in the rate of surgical site infections between patients who discontinued (3.06 percent) versus continued their bDMARDs (2.90 percent). The rates of delayed wound healing were also similar between those discontinuing (2.28 percent) and continuing their bDMARDs (0.99 percent). Subgroup analysis of patients undergoing total joint arthroplasty also showed no significant difference in the rate of surgical site infection.

However, patients who discontinued their bDMARDs were substantially more likely to experience a disease flare during the postoperative period: 25.71 percent compared with 7.32 percent among patients who continued their bDMARDs. The pooled analysis suggested a 78 percent reduction in the odds of having a flare for patients who continued bDMARD therapy.

Disease flares compromise patient rehabilitation following orthopaedic surgery. In addition, patients who experience a flare often require treatment with corticosteroids, introducing an additional risk of infection. “It is therefore important to balance the risk of flares against the risk of infection if bDMARDs are continued during the perioperative period,” Dr. van Duren and coauthors write.

The researchers note that their review is among the first “to comprehensively investigate the effect of continuing or discontinuing bDMARDs perioperatively across inflammatory diseases in patients undergoing orthopaedic surgery.” However, although the analysis included data on a large number of patients, the ability to draw conclusions is limited by the “generally low” quality of the available studies, as reflected by the inconsistency of current guidelines regarding perioperative bDMARD discontinuation. Dr. van Duren and colleagues emphasize the need for randomized controlled trials “to provide definitive answers in this important area.”

Biologics are treatment derived from a biological process rather than being manufactured chemically. Biologics can be broadly classified into two major groups; Anti-Tumour necrosis factor alpha and others.

Among various cytokines, Tumour necrosis factor alpha is the main target of for many biologics Therefore, will start with the anti-tumour necrosis factor. In the TNFα producing cells such as phagocytes the transmembrane TNFα is detached from the cell membrane by the action of the TNF converting enzyme The free-floating molecule is now called soluble TNFα The soluble TNFα molecules traverse to the TNFα responsive cells Where they bind to specific receptors called TNF receptors abbreviated as TNFR. There are two subtypes of TNF receptors TNFR1 And TNFR2 Soluble and transmembrane TNF could bind to either TNFR1 or TNFR2

But transmembrane TNFα prefer binding to TNFR2 TNFR1 are expressed in almost all body cells except erythrocytes Whereas TNFR2 are strictly expressed in the immune cells. Generally, activation of TNFR1 lead to sequences of biological reactions end up with cell apoptosis. On the other hand, activation of TNFR2 promotes cell proliferation. Both soluble and transmembrane TNFα are the main targets for many biologics The anti-TNFα biologics can be functionally divided into two groups Anti TNFα antibodies And Soluble TNFα receptors. The anti TNFα antibodies can be further divided into Chimeric antibodies Fully humanized antibodies Fully humanized with Poly Ethylene Glycol antibodies Infliximab drug is an example of chimeric antibodies produced from mouse myeloma. Adalimumab and golimumab are biologics generated completely from human antibodies The certolizumab is a unique biologic where polyethylene glycol Fab segment is connected to the human monoclonal antibody

Etanercept drug contains soluble TNFR2 receptors that bind and inactivate TNFα. Over the last twenty years the biologics have significantly improve the remission rates in many rheumatoid arthritis patients However, 40% of patients do not respond to biologics treatment To enhance the effectiveness of biologics in resistant patients The next generation of biologics should work more selectively They should block TNFR1 and activate the TNRF2 Now we will go through the other biologics These biologics attack either cytokines or cellular targets

The targeted cytokines include IL-6 IL-1 And IL-17 Whereas T cell and B cells are the main cellular targets IL-6 is attacked by tocilizumab antibodies While IL-1 receptors are blocked by anakinra biologic. Secukinumab is IL-17 antibody. T cell are deactivated by abatacept Whereas B cells are depleted rituximab biologics. Unfortunately, the cost of biological treatment is very expensive The one-year treatment course for one patient can cost up to £10 000 Therefore, after the end of patency of famous biologics many biosimilars have been introduced to the clinical practice Biosimilars Have similar structures, mechanism of actions, clinical efficacy and side effects of original biologics Fortunately, they cost much less than the original biologics Dozens of biosimilars have been licenced for clinical practice worldwide and hundreds are tested in clinical trials