RHEUMATOID
ARTHRITIS (RA)
TIRSIT KETSELA ([Link], MSC IN CLINICAL PHARMACY)
DECEMBER 2024
12/05/25 1
DEFINITION
• is a chronic and progressive autoimmune
disorder that primarily affects the joints.
• the immune system mistakenly attacks the
body’s own tissues, specifically the lining of
the joints (synovium), leading to inflammation,
pain, and damage.
• It affects joint linings, causing painful
swelling. Over long periods of time, the
inflammation can cause bone erosion and12/05/25 2
joint deformity.
CONT.…
• Key Features
• Inflammation: persistent inflammation in affected
joints, which can lead to swelling, redness, warmth,
and stiffness.
• Joint Damage: Over time, the inflammation can
erode cartilage and bone, leading to joint
deformities and loss of function.
• Symmetrical Pattern: affects joints
symmetrically (e.g., both wrists, knees, or hands
are usually affected).
• Systemic Impact: is not limited to joints; it can
also affect other parts of the body.
• Chronic Nature: symptoms may come and go
12/05/25 3
(flares and remissions), but the disease is
generally long-term.
EPIDEMIOLOGY
• RA is estimated to have a prevalence of 1%
• Can occur at any age, with increasing
prevalence up to the seventh decade of life.
• The disease is 3 times more common in
women.
• In people ages 15 to 45 years, women
predominate by a ratio of 6:1
• But, the sex ratio is approximately equal
among patients in the first decade of life and
in those older than age 60 years. 12/05/25 4
PATHOPHYSIOLOGY
• RA results from a dysregulation of the humoral
and cell-mediated components of the immune
system.
• Most patients produce antibodies called
rheumatoid factors
• Immunoglobulins (igs) can activate the
complement system, which amplifies the
immune response by enhancing phagocytosis,
12/05/25 5
and release of lymphokines.
CONT’D…
• Nonspecific immune response to tissues.
• Chronic inflammation of the synovial tissue
lining the joint capsule.
• Proliferation of synovial tissue leading to
invasion of the cartilage and bone surface.
• Erosions of bone and cartilage leading to
destruction of the joint.
12/05/25 6
CLINICAL PRESENTATIONS
• Joint pain and stiffness of more than 6 weeks'
duration
• Nonspecific symptoms of fatigue, weakness,
low-grade fever, loss of appetite.
• Joint stiffness typically worse in the morning
• Joint swelling, erythematous, and warmth
• Muscle pain and fatigue may also be present.
12/05/25 7
CONT.…
•Joint deformity is generally seen late in the
disease
• Chronic joint deformities
•Extra-articular involvements
•Joint involvement tends to be symmetric and
affect
• The small joints of the hands, wrists, and
feet;
• The elbows, shoulders, hips, knees, and
12/05/25 8
ankles.
12/05/25 9
12/05/25 10
DIAGNOSIS
• Rheumatoid factor (RF) detectable in 60% to 70%.
• Rheumatoid factors are proteins produced by
immune system that can attack healthy tissue.
• Normal less than 15 Iu/ml
• Elevated erythrocyte sedimentation rate (ESR)
and c-reactive protein
• Joint fluid aspiration may show increased white
blood cell counts
• Joint radiographs may show joint space
12/05/25 11
narrowing or erosions.
MANAGEMENT
Goals
• Induce a complete remission
• Reduce joint swelling, stiffness, and pain
• Preserve range of motion and joint function
• Improve quality of life
• Prevent systemic complications
12/05/25 12
CONT.….
Non-pharmacologic
•Adequate rest, weight reduction if obese,
physical therapy, and use of assistive devices.
•In sever condition, surgical procedures such
as tendon repair and joint replacements.
•Patient education
12/05/25 13
CONT.…
Pharmacological
•The recommended drug therapy is based
on disease duration, activity, and
prognosis
•In general, patients with less active
disease and good prognostic indicators
may be treated With oral agents as
monotherapy.
12/05/25 14
CONT.…
•Medications aimed at
• controlling symptoms
• slowing disease progression
• preventing joint damage
•Those with high disease activity and/or
poor prognostic features are candidates
• For combination therapy
12/05/25 15
CONT.…
[Link]-Modifying Antirheumatic Drugs
(DMARDs)----- slow disease progression and
prevent joint damage.
[Link] Anti-Inflammatory Drugs
(NSAIDs)---- reduce pain and inflammation
[Link]--- short-term symptom relief
or during disease flares
[Link] Pains ---- For symptom control, especially
when inflammation is not severe
12/05/25 16
CONT…
• Disease-modifying antirheumatic
drugs (DMARDs)
• modify the underlying disease process
rather than just relieving symptoms.
• They work to slow disease
progression, reduce inflammation, and
prevent joint damage.
12/05/25 17
CONT…
• categorized as either
• Non biologic disease-modifying anti
rheumatic drugs (DMARDs)
• Biologic DMARDs, which include
• Tnf-α inhibitor biologics
• non-tnf biologics
12/05/25 18
CONT…
• categorized as either
• Non biologic disease-modifying anti
rheumatic drugs (DMARDs)
• Biologic DMARDs, which include
• Tnf-α inhibitor biologics
• non-tnf biologics
12/05/25 19
CONT…
• Traditional DMARDs target the entire
immune system, whereas biologics work
by targeting specific steps in the
inflammatory process,
• Both non biologic and biologics
DMARDs can slow disease progression
12/05/25 20
CONT.….
• DMARDs should be started within the first 3
months of symptom onset.
• First-line DMARDs include
• methotrexate (mtx),
• hydroxychloroquine,
• Sulfasalazine
• leflunomide.
12/05/25 21
CONT.….
• Biologic agents are effective for patients who
fail treatment with other DMARDs
• Biologic agents with disease-modifying
activity include
• the anti-Tumor necrosis factor/TNF agents
(etanercept, infliximab, adalimumab)
• the IL-1 receptor antagonist (anakinra, and
rituximab), which depletes peripheral B
12/05/25 22
cells.
12/05/25 23
In early RA (<6 months)
Poor prognosis is defined as limitation in function,
extra articular findings (rheumatoid nodules,12/05/25
vasculitis,
24
rheumatoid lung findings, erosions on radiograph)
RX… IN EARLY RA (>6 MONTHS)
Poor response is defined as a deterioration of disease
activity or the patient continues with moderate to high
12/05/25 25
disease activity after 3 months of therapy
CONT.…
• Some biologic agents are contraindicated in
the setting of hepatitis or malignancies
because of immunosuppression.
• Etanercept, an anti-tnf biologic, is the only
agent recommended for possible treatment
in patients with hepatitis c
• Rituximab is preferred in patients with
previously treated solid malignancies, skin
cancers, or lymphoproliferative malignancies
12/05/25 26
12/05/25 27
12/05/25 28
12/05/25 29
Clinical Monitoring of Drug Therapy in Rheumatoid
Arthritis
12/05/25 30
12/05/25 31
CONT.…
EVALUATION OF RX OUTCOME
•Clinical signs and symptoms of
improvement
•Periodic joint radiographs
•Laboratory monitoring for detecting and
preventing adverse drug effects
•Presence of symptoms related to adverse
12/05/25 32
drug effects.
QUESTIONS
12/05/25 33
GOUT AND HYPERURICEMIA
12/05/25 34
DEFINITION
• Gout type of inflammatory arthritis caused by the
deposition of uric acid crystals in joints and
surrounding tissues.
• is a disease spectrum including
hyperuricemia, recurrent attacks of acute
arthritis associated with monosodium
urate(msu) crystals in leukocytes found
• In synovial fluid, in tissues (tophi),
interstitial renal disease ,in and around
12/05/25 35
joints and uric acid nephrolithiasis.
CONT.….
• Uric acid
• a chemical produced in the body as a byproduct
of the breakdown of purines, which are
substances found in some foods and are also
naturally present in cells.
• Antioxidant Role: has antioxidant properties and
helps neutralize harmful free radicals in the body.
• Normally, uric acid dissolves in the blood,
12/05/25passes
36
through the kidneys, and is excreted in urine.
CONT…
• Hyperuricemia may be an asymptomatic
condition with abnormal urate concentration
(greater than 7.0 mg/dl) and associated with
an increased risk for gout.
• Hyperuricemia does not always lead to gout,
and many patients with hyperuricemia
remain asymptomatic.
12/05/25 37
CLASSIFICATION OF HYPERURICEMIA
12/05/25 38
Purine metabolism. (HGPRT, hypoxanthine-guanine phosphoribosyltransferase;
PRPP, phosphoribosyl pyrophosphate.)
CONDITIONS ASSOCIATED WITH
HYPERURICEMIA
12/05/25 39
ETIOLOGY
• Uric acid is the end product of the
degradation of purines and is regarded as a
waste product, 2/3 excreted in urine.
• Purines originate from three sources:
dietary purine, conversion of tissue nucleic
acid to purine nucleotides, and de novo
synthesis of purine bases.
12/05/25 40
CONT…
• Humans have higher uric acid levels
than other mammals because
they do not express the enzyme
uricase, which converts uric acid into
the more soluble allantoin
• Excess accumulation urate in gout may
result from either overproduction or
underexcretion.
12/05/25 41
CONT…
• Uric acid may also be overproduced as a consequence
of increased breakdown of tissue nucleic acids, as
with myeloproliferative, lymphoproliferative
disorders, and cytotoxic drugs.
• Drugs that decrease renal clearance of uric acid
(diuretics, nicotinic acid, salicylates (less than 2
g/day), ethanol, pyrazinamide, levodopa, ethambutol,
cyclosporine, and cytotoxic drugs)
12/05/25 42
PATHOPHYSIOLOGY
• Deposition of urate crystals in synovial fluid results
• in an inflammatory process involving chemical
mediators (vasodilation, increased vascular
permeability, complement activation, and
chemotactic activity)
• Phagocytosis of urate crystals by leukocytes
results in rapid lysis of cells and a discharge of
proteolytic enzymes
• Intense joint pain, erythema, warmth, and swelling
12/05/25 43
CLINICAL PRESENTATION
• Acute attacks of gouty arthritis are
characterized by rapid onset of excruciating
pain, swelling, and inflammation
• Typically monoarticular at first (first
metatarsophalangeal joint) then, the insteps,
ankles, heels, knees, wrists, fingers, and
elbows.
12/05/25 44
CONT….
• Attacks commonly begin at night, with the
patient awakening from sleep with
excruciating pain.
• The affected joints are erythematous, warm,
and swollen. Fever and leukocytosis are
common.
12/05/25 45
CONT…
• Acute attacks of gouty arthritis is
precipitated by stress, trauma, alcohol
ingestion, infection, surgery, rapid
lowering of serum uric acid by ingestion of
uric acid–lowering agents, and ingestion of
certain drugs known to elevate serum uric
acid concentrations.
12/05/25 46
12/05/25 47
CONT’D…
• CHRONIC TOPHACEOUS GOUT
• Tophi ---------hard, chalky lumps
• Usually develops after 10 or more years
of acute intermittent gout.
• refers to stage of deposition of urate,
inflammatory cells and foreign body giant
cells in the tissues.
• Deposits may be in tendons or ligaments.
12/05/25 48
12/05/25 49
DIAGNOSIS
• Presumptive diagnosis- signs and
symptoms, and response to treatment.
• Definitive diagnosis is accomplished by
aspiration of synovial fluid from the
affected joint and identification of
intracellular crystals of monosodium
urate monohydrate in synovial fluid
leukocytes.
12/05/25 50
CLINICAL MANIFESTATIONS OF GOUT
12/05/25 51
TREATMENT
• The goals
• Terminate the acute attack
• Prevent recurrent attacks of gouty
arthritis
• Prevent complications
12/05/25 52
CONT…
NON-PHARMACOLOGIC THERAPY
• There are limited effective
nonpharmacologic therapies for
an acute gout attack;
• Therefore, they are
recommended strictly as
adjunctive treatment.
• Local ice application is the most
effective
12/05/25 53
CONT…
• Reduce their intake of foods
high in purines (e.g.,organ
meats), avoid alcohol, increase
fluid intake, and lose weight if
obese.
• Joint rest for 1 to 2 days should
be encouraged, and local
application of ice
12/05/25 54
PHARMACOLOGICAL RX
• For most patients, acute attacks of
gouty arthritis may be treated
successfully with
• Nonsteroidal anti-inflammatory
drugs (NSAIDs)
• corticosteroids, or
• colchicine
• guidelines recognize these three
modalities as first-line
monotherapy for the treatment of
12/05/25 55
acute gout.
CONT….
• Treatment should commence
within 24 hours of the onset of an
attack and continued until
complete resolution.
• Resolution of an acute attack for
most patients generally occurs
within 5 to 8 days after initiating
therapy
12/05/25 56
CONT…
Colchicine
•is an antimitotic drug that is highly
effective at relieving acute attacks of
gout.
•When begun within the first 24 hours
of an acute attack, produces a
response in two thirds of patients
within hours of administration.
12/05/25 57
CONT…
• the ACR guidelines advocate use of
colchicine for treatment of acute gout only
if started within 36 hours of attack onset.
• the FDA approved a 0.6-mg tablet of
colchicine for oral use
• Dose-dependent GI adverse effects (nausea,
vomiting, and diarrhea) and non-GI adverse
effects of neutropenia and axonal
neuromyopathy.
12/05/25 58
CONT…
• IV colchicine should be avoided
because it is associated with serious
adverse effects (e.g., bone marrow
suppression, tissue necrosis from
local extravasation, disseminated
intravascular coagulation,
hepatocellular toxicity, and renal
failure)
12/05/25 59
CONT…
CORTICOSTEROIDS
•to treat acute attacks of gouty arthritis,
but they are reserved primarily for
patients with a contraindication or who
are unresponsive to NSAID or colchicine
therapy.
•The recommended dose is prednisone 30
to 60 mg (or an equivalent dose of
another corticosteroid) orally once daily
for 3 to 5 days.
•A single intramuscular injection of a
long-acting corticosteroid (e.g.,
methylprednisolone acetate) can be used
12/05/25 60
as an alternative to oral.
HYPERURICEMIA IN GOUT…RX
• Recurrent gout attacks can be prevented by
maintaining low uric acid level.
•Nonpharmacologic Therapy
• Patient education, is critical first step in
the management of hyperuricemia
• Weight loss…. enhance renal excretion of
urate
• Restriction of alcohol intake
12/05/25 61
CONT…
• encourage the consumption of
vegetables and low-fat dairy products,
which have been shown to have urate-
lowering effects
• Limiting consumption of high-fructose
corn syrup and purine-rich foods
(organ meats and some seafood)
12/05/25 62
CONT…
pharmacologic urate-lowering therapy.
• the occurrence of two or more gout attacks
per year
• the presence of one or more tophus,
chronic kidney disease (stage 2 or
worse)
• The goal of initiating urate-lowering
therapies is to
• achieve and maintain a serum uric acid
concentration of less than 6 mg/dL and
preferably below 5 mg/dL if signs and
symptoms of gout persist 12/05/25 63
CONT…
• Reduction of serum urate
concentrations can be accomplished
pharmacologically by
• decreasing the synthesis of uric
acid----xanthine oxidase inhibitors
• increasing the renal excretion of
uric acid----uricosurics
12/05/25 64
CONT…
• Xanthine oxidase inhibitors inhibit the
enzyme xanthine oxidase, which plays a
key role in the production of uric acid.
• Allopurinol
• Starting Dose: 100 mg once daily
(may start at 50 mg daily in
patients with chronic kidney
disease)
• Maintenance Dose: 100–300 mg
once daily. 12/05/25 65
CONT…
12/05/25 66
CONT…
• xanthine oxidase inhibitors are
recommended as first-line therapy.
• Probenecid, a potent uricosuric therapy,
is recommended as an alternative first-
line therapy
• In refractory cases, combination
therapy is suggested.
• Finally, in severe cases in which the
patient cannot tolerate or is not
responding to other therapies---
pegloticase is recommended. 12/05/25 67
CONT…
• Initiation of urate-lowering therapy can
prompt an acute attack of gout due to
remodeling of urate crystal deposits in
joints as a result of rapid lowering of
urate concentrations.
• As such, prophylactic anti-inflammatory
pharmacotherapy should be employed to
• prevent gout attacks
• assist in ensuring patient adherence
12/05/25 68
CONT…
• low-dose oral colchicine (0.6 mg twice
daily) and low-dose NSAIDs (e.g., naproxen
250 mg twice/day) as first-line prophylactic
therapies
• Low-dose corticosteroid therapy (e.g., ≤10
mg/day prednisone) is recommended as an
alternative in patients
• with intolerance, contraindication, or lack
of response to first-line therapy 12/05/25 69
CONT’D…
• Pharmacologic prophylaxis should be
continued for at least 3 months after
achieving target serum uric acid or 6
months total, whichever is longer
12/05/25 70
ALGORITHM FOR MANAGEMENT OF AN
ACUTE GOUT ATTACK
12/05/25 71
12/05/25 72
DOSAGE REGIMENS OF NSAIDS FOR
TREATMENT OF ACUTE GOUTY ARTHRITIS
12/05/25 73
Algorithm for management of hyperuricemia in gout.
12/05/25 74
CASE STUDY
CHIEF COMPLAINT
• “I CAN’T WALK BECAUSE MY ANKLE IS KILLING ME.”
HPI
• mr a.z is a 66-year-old man with a history of dyslipidemia who
presents to the emergency department of his local hospital. he is
suffering from sudden onset of pain in his left ankle that woke
him up at 5:00 am this morning. over the last 2 hours, his left
ankle has become red and swollen, and the pain from the joint is
so bad that he cannot walk. he relates no trauma or injury to the
ankle and has not exerted himself more than usual in the recent
past. he also denies having experienced these symptoms
12/05/25 75
previously.
PMH .
• Dyslipidemia, peptic ulcer disease (duodenal ulcer discovered
6 months ago), and obesity
SH
• The patient drinks “a can of beer or two” daily. He does not
smoke or use illicit drugs.
MEDS
• Extended-release niacin (niaspan) 1,000 mg po at bedtime,
started 2 months ago
Omeprazole 20 mg po daily
ALL
• Simvastatin and atorvastatin (both caused severe muscle
aches, and the patient was forced to discontinue them)
12/05/25 76
PHYSICAL EXAMINATION
GEN
• A healthy appearing, obese, black male in acute distress
VS
• BP 135/88, P 100, RR 18, T 37.5°C; WT 97 KG, HT 1.60M
SKIN
• No rashes or other dermatologic abnormalities. Has a “skull” tattoo on
his left arm.
HEENT
• Pink conjuctiva/ears clear of redness or inflammation
NECK/LYMPH NODES
• NEGATIVE FOR LYMPH NODE SWELLING OR MASSES
LUNGS/THORAX
• clear to auscultation bilaterally, symmetric movement with inspiration
ABD
• OBESE, BUT SOFT, NONTENDER. POSITIVE BOWEL SOUNDS IN ALL
12/05/25 77
QUADRANTS.
MS/EXT
• Left ankle with 3+ edema around joint, contrasted erythema
present, and very warm to touch. Joint is exquisitely painful
with patient relating the pain as currently a 10/10 (on a 1–10
scale with “1” being no pain and “10” being the worse pain
the patient has ever suffered). No swelling of any other
joints including great toe. No signs of tophi present.
ANKLE RADIOGRAPH: NEGATIVE FOR BREAK OR DAMAGE
ASPIRATED FLUID FROM ANKLE JOINT TAP: >50 WBC/HPF,
CONTAINING
NEGATIVELY BIREFRINGENT MONOSODIUM URATE CRYSTALS.
12/05/25 78
LAB.
Na 138 mEq/L Hgb 15.1 g/dL WBC 12.8 × 103/mm3
Lipid panel (fasting):
K 3.9 mEq/L Hct 45% Neutros 88%
HDL-C 25 mg/dL
Cl 101 mEq/L RBC 4.9 × 106/mm3 Bands 0%
Trig 280 mg/dL
CO2 23 mEq/L Plt 210 × 103/mm3 Eos 1%
LDL-C 99 mg/dL
BUN 9 mg/dL MCV 81 μm3 Lymphs 10%
T. chol 180 mg/dL
SCr 1.0 mg/dL MCHC 35 g/dL Monos 1%
Glu 105 mg/dL ESR 45 mm/h RF negative
Uric acid 11.6 mg/dL
12/05/25 79
.
• Assessment ?
• Patient’s drug therapy problems?
• Symptoms, signs, laboratory values indicative of
acute gouty arthritis?
• Goals of pharmacotherapy?
• Nondrug therapies?
• Pharmacotherapeutic modalities of acute gouty
arthritis?
• Is the patient candidate for prophylactic therapy?
• What drug, dosage form, schedule, and duration of
therapy are best ?
• Which clinical and laboratory parameters should be
monitored?
12/05/25 80
• What information should be provided to the
patient?
QUESTIONS
12/05/25 81