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Revolutionary Treatments for Rheumatoid Arthritis: Biologics and Targeted Synthetic DMARDs

Picture credit: istockphoto.com/portfolio/Doucefleur

Rheumatoid arthritis plagues approximately 3 to 4 percent of the female populace and 1 to 2 percent of their male counterparts. As an autoimmune affliction, it involves the body’s defense mechanism—its immune system—assaulting healthy tissues rather than targeting foreign adversaries such as pathogens. Inflammation is the primary weapon, culminating in swelling, discomfort, and the progressive erosion of joint tissue.

The American College of Rheumatology regularly promulgates updated treatment protocols, informed by novel pharmaceuticals and clinical investigations. Although the disease-modifying antirheumatic drug (DMARD) methotrexate remains the preeminent choice, recent developments in biologic and targeted synthetic DMARDs have expanded the therapeutic spectrum.

Biologics, engineered antibodies of genetic origin, obstruct specific phases in the immune system’s route to inflammation. The inaugural biologic sanctioned for rheumatoid arthritis obstructed a cytokine variety known as tumor necrosis factor. Cytokines, proteins essential for inducing inflammation, rely on the immune system. These biologics have since earned the moniker of tumor necrosis factor (TNF) inhibitors. Presently, numerous other biologic classifications obstruct distinct pathways.

Targeted synthetic DMARDs represent the most recent therapeutic innovations. The predominant variant for rheumatoid arthritis is the Janus kinase (JAK) inhibitor. Unlike TNF inhibitors, JAK inhibitors thwart multiple cytokines required by immune cells to exacerbate inflammation. Each of these pharmaceuticals possesses its unique advantages and drawbacks:

Traditional synthetic DMARDs tend to be safe, efficacious, cost-effective, and predominantly available in tablet form. Biologics necessitate administration via injection or infusion and might elevate the risk of severe infections; however, they potentially surpass conventional synthetic DMARDs in strength. Targeted synthetic DMARDs exhibit comparable risks and efficacy to biologics, with the added benefit of oral consumption.

Therapeutic Recommendations

Upon receiving a rheumatoid arthritis diagnosis, the initial course of action involves your healthcare professional assessing your disease activity level—low, moderate, or high. Subsequently, a six-month target or treatment objective must be established. Although symptom-free remission is achievable for roughly one-third of patients, low disease activity is typically the primary goal. Treatment is administered in three stages, contingent upon disease activity:

Step 1. For patients exhibiting low disease activity, a single conventional synthetic DMARD may be prescribed. Hydroxychloroquine is often the preferred option, as it is well-tolerated by most individuals. As hydroxychloroquine and sulfasalazine do not suppress the immune system, they may be prioritized over methotrexate for mild cases or instances involving a history of immune-sensitive cancers like melanoma. Individuals testing negative for RA antibodies in blood tests, indicating seronegative RA, may be predisposed to less aggressive disease progression. Hydroxychloroquine or sulfasalazine could be suitable choices for such patients.

Step 2. If low disease activity is not sustained after six months or disease activity commences at moderate to high levels, methotrexate monotherapy is advised. Approximately 50 percent of patients achieve their target utilizing methotrexate monotherapy. Given its comparable efficacy, ease of administration, and cost-effectiveness, methotrexate is recommended over biologic monotherapy. If the target remains unmet, a transition from oral methotrexate to subcutaneous injections may be considered. Failing that, step three entails incorporating additional DMARDs.

Step 3. For patients unable to reach their objectives with methotrexate alone, two alternatives are suggested. The first is triple therapy, encompassing methotrexate, hydroxychloroquine, and sulfasalazine. The second comprises methotrexate in conjunction with a biologic (typically a TNF inhibitor) or a targeted synthetic DMARD (a JAK inhibitor). Generally, TNF inhibitors exhibit a superior safety profile. Patients requiring further assistance to maintain their target may transition to an alternate biologic or targeted synthetic DMARD. However, as sufficient research is currently unavailable, selecting the optimal treatment remains speculative. Patients frequently inquire about initiating biologic monotherapy rather than methotrexate. Conflicting research findings, with some studies reporting heightened efficacy for biologics and others refuting these claims, account for this uncertainty.

Historically, concerns arose that biologics might heighten the risk of white blood cell cancer; however, recent investigations have not corroborated these fears. Despite this, biologics continue to increase the likelihood of rare but severe infections and remain expensive. Consequently, they are not employed as initial therapy.

A Nuanced Approach to Tapering Treatment: Persevering Amidst the Ebb and Flow of Rheumatoid Arthritis

Delving into the intricacies of managing patients with multiple medications in the context of sustained remission or reduced disease activity, for a period not less than six months, elucidates the possibility of attenuating drug dosages. In some instances, a gradual discontinuation of certain medications is plausible. However, ceasing therapeutic interventions altogether is ill-advised due to the looming risk of disease flare-ups.

For patients flourishing on TNF inhibitors, it’s crucial to comprehend the implications of tapering; a relapse rate ranging between 30 to 50 percent has been documented. Contrastingly, with other biologic agents, a shift to monotherapy employing methotrexate is viable. In scenarios where triple therapy is in effect, sulfasalazine’s removal takes precedence, succeeded by hydroxychloroquine’s withdrawal.

Lifestyle Edicts: Embarking on the Path to Holistic Wellness

The adoption of a Mediterranean-style diet acts as a bulwark against heart disease, an affliction more prevalent in individuals with RA. Exercise, coupled with strength training, serves a dual purpose: maintaining a salubrious weight and fortifying muscles to buttress joints. Obesity exacerbates RA, as does smoking. Methotrexate users should abstain from alcohol to circumvent heightened liver damage risk.

Rheumatology’s Vanguard: The American College of Rheumatology’s Ever-evolving Guidelines

The American College of Rheumatology’s unwavering commitment to amending RA treatment guidelines in response to groundbreaking research or novel medications has borne fruit. In 1950, the life expectancy of a person with RA languished around 67 years; today, it stands at an impressive 80 years. Living with RA has undergone a metamorphosis. With judicious treatment and care, a vast majority of RA patients can now savor an enhanced quality of life, remain gainfully employed, and partake in a plethora of physical and social activities.

A Retrospective: The Evolution of RA Drug Therapies

Rheumatoid arthritis (RA), in the absence of disease-modifying antirheumatic drugs (DMARDs), mercilessly debilitated individuals by ravaging their joints. A turning point materialized in the 1980s with the FDA’s approval of methotrexate, a DMARD heralding a new era in RA treatment and prognosis. Hydroxychloroquine and sulfasalazine emerged as fellow DMARD pioneers. Prior to the DMARD revolution, glucocorticoids – a class of steroids – offered the sole therapeutic recourse for RA. While these drugs curtailed joint swelling and pain, they failed to halt irreversible joint destruction. Moreover, their use was circumscribed by adverse effects, warranting a cautious, as-needed approach. DMARDs empowered RA patients to achieve low disease activity, engendering a paradigm shift from deferred treatment to proactive intervention to thwart irreversible joint damage.

 

Written by ioiadmin

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